US20040230309A1 - In-situ formed intervertebral fusion device and method - Google Patents

In-situ formed intervertebral fusion device and method Download PDF

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Publication number
US20040230309A1
US20040230309A1 US10/778,684 US77868404A US2004230309A1 US 20040230309 A1 US20040230309 A1 US 20040230309A1 US 77868404 A US77868404 A US 77868404A US 2004230309 A1 US2004230309 A1 US 2004230309A1
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US
United States
Prior art keywords
load
balloon
component
bearing
osteobiologic
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Abandoned
Application number
US10/778,684
Inventor
Thomas DiMauro
Michael Slivka
John Malone
Bradley Moore
Hassan Serhan
Sudhakar Kadiyala
Charles Bartish
Hal Woodrow
William Rohr
James Kelly
Kevin Cooper
Lauren Aquino
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
DePuy Spine LLC
DePuy Synthes Products Inc
Original Assignee
DePuy Spine LLC
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority to US10/778,684 priority Critical patent/US20040230309A1/en
Application filed by DePuy Spine LLC filed Critical DePuy Spine LLC
Assigned to DEPUY SPINE, INC. reassignment DEPUY SPINE, INC. ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: ROHR, WILLIAM L., KELLY, JAMES EDWARD, DIMAURO, THOMAS M., COOPER, KEVIN, WOODROW, HAL BRENT, AQUINO, LAUREN, BARTISH, CHARLES M., JR., KADIYALA, SUDHAKAR, MALONE, JOHN DANIEL, MOORE, BRADLEY THOMAS, SERHAN, HASSAN, SLIVKA, MICHAEL ANDREW
Publication of US20040230309A1 publication Critical patent/US20040230309A1/en
Priority to US13/490,743 priority patent/US11432938B2/en
Assigned to DePuy Synthes Products, LLC reassignment DePuy Synthes Products, LLC CHANGE OF NAME (SEE DOCUMENT FOR DETAILS). Assignors: HAND INNOVATIONS LLC
Assigned to HAND INNOVATIONS LLC reassignment HAND INNOVATIONS LLC ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: DEPUY SPINE, LLC
Assigned to DEPUY SPINE, LLC reassignment DEPUY SPINE, LLC CHANGE OF NAME (SEE DOCUMENT FOR DETAILS). Assignors: DEPUY SPINE, INC.
Assigned to DePuy Synthes Products, Inc. reassignment DePuy Synthes Products, Inc. CHANGE OF NAME (SEE DOCUMENT FOR DETAILS). Assignors: DePuy Synthes Products, LLC
Priority to US14/632,875 priority patent/US9730803B2/en
Priority to US14/640,741 priority patent/US9439776B2/en
Priority to US14/668,576 priority patent/US9801729B2/en
Priority to US14/674,070 priority patent/US9439777B2/en
Priority to US14/684,959 priority patent/US9333091B2/en
Priority to US14/856,716 priority patent/US9814589B2/en
Priority to US14/875,983 priority patent/US9808351B2/en
Priority to US14/886,302 priority patent/US9788963B2/en
Priority to US14/886,362 priority patent/US9814590B2/en
Priority to US14/934,289 priority patent/US9724207B2/en
Priority to US15/074,725 priority patent/US20160199196A1/en
Priority to US15/188,179 priority patent/US10085843B2/en
Priority to US15/201,472 priority patent/US10575959B2/en
Priority to US15/206,734 priority patent/US10786361B2/en
Priority to US15/209,080 priority patent/US10492918B2/en
Priority to US15/218,362 priority patent/US10583013B2/en
Priority to US15/219,360 priority patent/US10433971B2/en
Priority to US15/226,367 priority patent/US10420651B2/en
Priority to US15/260,465 priority patent/US9925060B2/en
Priority to US15/331,978 priority patent/US10639164B2/en
Priority to US15/648,053 priority patent/US10555817B2/en
Priority to US15/806,363 priority patent/US10405986B2/en
Priority to US15/825,240 priority patent/US10376372B2/en
Priority to US16/133,361 priority patent/US11096794B2/en
Priority to US16/548,239 priority patent/US11207187B2/en
Abandoned legal-status Critical Current

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    • A61L2300/00Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/20Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials
    • A61L2300/252Polypeptides, proteins, e.g. glycoproteins, lipoproteins, cytokines
    • A61L2300/256Antibodies, e.g. immunoglobulins, vaccines
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    • A61L2300/00Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/40Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
    • A61L2300/404Biocides, antimicrobial agents, antiseptic agents
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    • A61L2300/00Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/40Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
    • A61L2300/412Tissue-regenerating or healing or proliferative agents
    • A61L2300/414Growth factors
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    • A61L2300/00Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/40Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
    • A61L2300/43Hormones, e.g. dexamethasone
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    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2300/00Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/60Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a special physical form
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    • A61L2430/00Materials or treatment for tissue regeneration
    • A61L2430/38Materials or treatment for tissue regeneration for reconstruction of the spine, vertebrae or intervertebral discs

Definitions

  • a leading cause of lower back pain arises from lumbar intervertebral disc pathology, including rupture or degeneration of the disc. Radicular pain in the lower extremities may be caused by the compression of spinal nerve roots by a bulging disc. Additionally, lower back pain may be caused by collapse of the disc and the dysarthrosis of an unstable or degenerative vertebral facet joint.
  • One proposed method of managing these problems is to remove the problematic disc and replace it with a porous device that restores disc height and allows for bone growth therethrough for the fusion of the adjacent vertebrae. These devices are commonly called “fusion devices.”
  • Intervertebral body fusion devices typically must carry extremely high loads (on the order of 1-4 kN) for a period of several months, or until fusion occurs. Accordingly, a fusion device or bone graft substitute designed for promoting bony fusion at another location in the body (such as long bone fusion) may not be suitable for use as an intervertebral body fusion device.
  • many bony fusion devices disclose the use of a gel such as a hydrogel as the structural carrier for an osteoinductive or an osteogeneic component.
  • such gels typically do not posses the stiffness or mechanical strength found to be required for lumbar intervertebral fusion devices.
  • a number of such prosthetic implants have been described for serving as an intervertebral disc, or nucleus pulposus, replacement, involving the delivery of prosthetic materials through a small diameter cannula no larger than is needed to perform an adequate discectomy. Therefore, the injectable prosthetic devices are typically delivered in a first fluid form and then harden to a second form once inside the disc space to span the disc space height and preferably fill the disc space following discectomy.
  • the requirements for a bone fusion system are very different from those of injectable prosthetic devices.
  • an intervertebral strut injectable into the disc space that can create or maintain a preferred spatial relationship between adjacent vertebral body endplates (curvature and distraction) and comprises an osteogenic component to promote bony fusion between the two adjacent vertebra.
  • the present invention relates to a device for intervertebral spinal fusion and method of making thereof.
  • the present invention is an orthopedic device for implanting between adjacent vertebrae comprising a generally arcuate balloon and a hardenable material within said balloon.
  • the present invention is an intervertebral spinal fusion device comprising at least one arcuate inflatable balloon whereby at least partially filling the balloon between two adjacent vertebrae at least partially restores a natural angle between the adjacent vertebrae, and wherein said arcuate balloon contains a load-bearing component within a lumen defined by the balloon.
  • the present invention is an intervertebral spinal fusion device comprising a anterior frame having an upper inflatable rim and a lower inflatable rim, and a rigid inflatable posterior frame attached to the upper and lower inflatable rims of the anterior frame.
  • the anterior frame is detachably connected to the first fluid communication means.
  • the posterior frame is detachably connected to the second fluid communication means.
  • the present invention is a method of implanting an intervertebral spinal fusion device, comprising the steps of (a) performing a discectomy while preserving an outer annular shell; (b) inserting an inflatable device that includes a deflated arcuate balloon into an intervertebral space; (c) directing an osteobiologic omponent into the deflated arcuate balloon in an amount sufficient to inflate the balloon and distract the disc space.
  • the present invention is a method of implanting an intervertebral spinal fusion device, comprising the steps of (a) inserting an inflatable device through a cannula into an intervertebral space, said inflatable device including an arcuate balloon connected to at least one fluid communication means, wherein said inflatable device upon expansion between two adjacent vertebrae at least partially restores a natural angle between the adjacent vertebrae; (b) orienting said inflatable device so that upon expansion a natural angle between vertebrae will be at least partially restored; (c) directing a load-bearing component into the inflatable device through the fluid communication means.
  • the present invention is a method of at least partially restoring a natural angle between two adjacent vertebrae, comprising the steps of (a) inserting an inflatable device through a cannula into an intervertebral space; (b) orienting said inflatable device so that upon expansion of the device a natural angle between vertebrae will be at least partially restored; and (c) expanding said inflatable device by directing a load-bearing component into said inflatable device.
  • the present invention is a method of delivering an osteobiologic material comprising (a) inserting an inflatable device into an intervertebral space wherein at least a portion of the device upon expansion has a substantially toroidal shape thereby forming an open cavity defined by an outer surface of the toroidal shape and having an axial dimension and a radial dimension; (b) orienting at least a portion of the device so that so that the axial dimension of the open cavity is substantially parallel to a major axis of a spinal column of a patient in which the device has been implanted; (b) inflating said inflatable device by directing a load-bearing component into said inflatable device; (c) directing an osteobiologic material into the open cavity, said material including at least one water-soluble material; (d) directing an aqueous fluid into into the open cavity defined by the inflated device thereby dissolving at least one said water-soluble material, and forming a porous matrix; and (e) delivering additional osteobiologic component
  • the present invention is a pharmaceutical composition
  • a pharmaceutically acceptable carrier or diluent and (a) at least one polymer flowable between 38° C. and 45° C. selected from the group consisting of homopolymers of poly( ⁇ -caprolactone), poly(p-dioxanone), or poly(trimethylene carbonate) or copolymers or mixtures thereof, or copolyesters of p-dioxanone or trimethylene carbonate and glycolide or lactide or mixtures thereof, and in particular, copolymers of p-dioxanone/glycolide, p-dioxanone/lactide, trimethylene carbonate/glycolide and trimethylene carbonate/lactide, or copolyesters of .epsilon.-caprolactone and glycolide or mixtures thereof, or mixtures of homopolymers of ⁇ -caprolactone and lactide; and (b) at least one growth factor resistant to den
  • the present invention is an intervertebral fusion device comprising an in-situ formed osteobiologic component comprising (a) a matrix having an internal surface defining an open porosity suitable for bone growth therethrough, and (b) an osteogenic component located within the open porosity.
  • the present invention is an intervertebral fusion device for providing bony fusion across a disc space, comprising (a) a strut having a upper surface for bearing against the upper endplate and a lower surface for bearing against the lower endplate, and (b) an in-situ formed osteobiologic component.
  • the present invention is an intervertebral fusion device for providing bony fusion across a disc space, comprising a strut comprising (a) an upper surface for bearing against the upper endplate, (b) a lower surface for bearing against the lower endplate, and (c) an injectable load bearing composition disposed between the upper and lower surfaces.
  • the present invention is an intervertebral fusion device comprising a matrix having an internal surface defining an open porosity suitable for bone growth therethrough, wherein the matrix is formed by a plurality of in-situ bonded beads.
  • the present invention is an intervertebral fusion device comprising a strut comprising (a) a first component comprising (i) a lower bearing surface adapted for bearing against a lower vertebral endplate, and (ii) an upper surface comprising a leading end, an angled middle portion and a trailing end; and (b) a second component comprising (i) an upper bearing surface adapted for bearing against an upper vertebral endplate and (ii) an upper surface comprising a leading end, an angled middle portion and a trailing end.
  • the angled portion of the first component mates with the angled portion of the second component.
  • the present invention is a kit for providing interbody fusion across an intervertebral disc space, comprising (a) a cannula defining an inner diameter; (b) a hardenable material capable of supporting intervertebral load; and (c) a flowable osteobiologic composition.
  • the present invention is an intervertebral fusion device for providing bony fusion across a disc space, comprising (a) a strut having a upper surface for bearing against an upper endplate and a lower surface for bearing against a lower endplate, the upper surface and lower surface defining a height therebetween, and (b) an in-situ formed osteobiologic component.
  • the height of the strut is no greater than the height of the disc space.
  • the present invention is a method of providing interbody fusion across an intervertebral disc space, comprising the steps of (a) providing a cannula defining an inner diameter; (b) moving a load bearing composition through the cannula and into the disc space to form a in-situ formed load bearing strut; and (c) moving an osteobiologic composition through the cannula and into the disc space to form an in-situ formed osteobiologic composition.
  • the present invention is an intervertebral fusion device for providing bony fusion across a disc space, comprising a strut comprising (a) an upper surface for bearing against the upper endplate and (b) a lower surface for bearing against the lower endplate.
  • the strut comprises an in-situ formed load bearing composition.
  • the present invention is an intervertebral fusion device for providing bony fusion across a disc space, comprising a strut comprising (a) an upper surface for bearing against the upper endplate, (b) a lower surface for bearing against the lower endplate, and (c) an in-situ formed load bearing composition disposed between the upper and lower surfaces.
  • the present invention is an intervertebral fusion device comprising (a) a strut have a shape memory and comprising (i) an upper surface for bearing against the upper endplate, (ii) a lower surface for bearing against the lower endplate, and (b) an in-situ formed osteobiologic component.
  • the present invention is an intervertebral fusion device comprising (a) a strut comprising an upper surface for bearing against the upper endplate and a lower surface for bearing against the lower endplate, and (b) an in-situ formed osteobiologic component comprising a matrix component having an internal surface defining a scaffold having open porosity suitable for bone growth therethrough, and an osteogenic component located within the open porosity.
  • the present invention is an intervertebral fusion device comprising a strut comprising an upper surface for bearing against the upper endplate and a lower surface for bearing against the lower endplate, and an in-situ formed osteobiologic component comprising an injectable matrix component, an an osteoinductve component embedded within the matrix.
  • the present invention is an intervertebral fusion device comprising a strut comprising an upper surface for bearing against the upper endplate a lower surface for bearing against the lower endplate, and an in-situ formed osteobiologic component comprising an injectable matrix component, and a porogen embedded within the matrix.
  • the present invention is an intervertebral fusion device comprising a strut comprising an upper surface for bearing against the upper endplate, a lower surface for bearing against the lower endplate, and an in-situ formed osteobiologic component comprising an expandable device defining a cavity, and an injectable osteobiologic composition located within the cavity.
  • the present invention is an intervertebral fusion device comprising a strut comprising an expandable device having a cavity, an upper surface for bearing against the upper endplate, a lower surface for bearing against the lower endplate, and an inner wall defining a through hole and an injectable load bearing composition located within the cavity, and an osteobiologic component located in the throughhole.
  • the present invention is an intervertebral fusion device comprising a strut comprising an upper surface for bearing against the upper endplate, and a lower surface for bearing against the lower endplate; and an in-situ formed osteobiologic component comprising an injectable, matrix component essentially free of monomer.
  • the present invention is an intervertebral fusion device for providing bony fusion across a disc space, comprising a strut comprising (a) an upper surface for bearing against the upper endplate, (b) a lower surface for bearing against the lower endplate, and (c) an in-situ formed load bearing composition disposed between the upper and lower surfaces and made of a material comprising a cross-linked resorbable polymer.
  • the advantages of the present invention are numerous.
  • One advantage is that the present invention makes possible minimally invasive surgical procedures to restore a natural angle and increase disc height between two adjacent vertebrae.
  • the same device used used to create distraction/lordosis can function as the intervertebral implant needed to maintain height and natural angle.
  • Another advantage is that the present invention makes possible a minimally invasive procedure to create in situ a structural scaffold filled with osteoinductive materials.
  • FIG. 1 is a plot of strength over time of a resorbable polymer and bone growth.
  • FIGS. 2 ( a ) through 2 ( e ) are schematic representations of preferred embodiments of a semicircular, circular, bilateral and generally crescent, arcuate, or toroidal shapes of the device of the present invention.
  • FIGS. 2 ( f ) and 2 ( g ) show a perspective and a top view, respectively, of a preferred embodiment of a device of the present invention.
  • FIG. 3( a ) and FIG. 3( b ) show a perspective and a top view, respectively, of a preferred method of the introduction of a cannula into the disc space.
  • FIG. 4( a ) and FIG. 4( b ) show a perspective and a top view, respectively, of a preferred method of the deployment of an inflatable device into the disc space through the cannula.
  • FIG. 5( a ) and FIG. 5( b ) show a perspective and a top view, respectively, of an embodiment of the present invention wherein the device comprises a generally toroidal balloon and the osteobiologic component is injected into an open cavity defined by the outer surface of the generally toroidal balloon.
  • FIG. 6( a ) and FIG. 6( b ) show a perspective and a top view, respectively, of an embodiment of the present invention comprising more than one balloon.
  • FIG. 7( a ) and FIG. 7( b ) show a perspective and a top view, respectively, of another embodiment of the present invention comprising more than one balloon.
  • FIG. 8( a ) and FIG. 8( b ) show an embodiments of the present invention comprising an arcuate inflatable balloon with reinforced walls.
  • FIGS. 9 ( a ) through ( d ) show an embodiment of an inflatable device and a method of inserting an inflatable device of the present invention into the disc space, wherein a pair of semi-circular flexible members is used for guiding the device.
  • FIGS. 10 ( a ) and 10 ( b ) represent plan and lateral views, respectively, of an embodiment of an inflatable device of the invention whereby a pair of semi-circular flexible upper and lower wall components, which can be used for guiding the device, are joined by an inflatable balloon.
  • FIGS. 11 ( a ) and ( b ) show an embodiment of the present invention wherein the device comprises four semi-circular flexible components for guiding the inflatable device into the disc space.
  • FIGS. 12 ( a ) and ( b ) show another embodiment of device of the present invention that includes guiding members.
  • FIGS. 13 ( a ) through ( d ) shows a preferred embodiment of the method of the present invention.
  • FIG. 13( a ) and FIG. 13( b ) show inserting a cannula into an intervertebral space, followed by inserting an inflatable balloon of a generally toroidal shape into an intervertebral space through the cannula. The balloon is expanded by directing a load-bearing component into said balloon.
  • FIG. 13( c ) shows injecting an osteobiologic component comprising a water-soluble component into an open cavity, defined by the outer surface of the balloon, and
  • FIG. 13( d ) shows dissolving the water-soluble component.
  • FIGS. 14 ( a ) and ( b ) show a top and a lateral view, respectively, of another embodiment of a device of the present invention employing a ramp.
  • FIG. 14( c ) is a cross section of the device of FIGS. 14 ( a ) and ( b ).
  • FIG. 14( d ) is a perspective view of the device of FIGS. 14 ( a )-( c ).
  • FIG. 15 shows one embodiment of a method of deployment of the device of FIGS. 14 ( a )-( d ).
  • FIG. 16 shows another embodiment of a mthod of deployment of the device of FIGS. 14 ( a )-( d ).
  • FIGS. 17 ( a ) and ( b ) show a particularly preferred embodiment of the device of the present invention in collapsed and expanded configuration, respectively.
  • the present invention relates to a vertebral fusion device for simultaneously distracting two adjacent vertebral bodies and delivering a flowable material into a disk space.
  • vertebral fusion refers to a medical procedure that results in maintaining separation between vertebrae.
  • vertebral fusion provides for bony ingrowth that fixes two adjacent vertebrae in a desired, for example, distracted and/or angulated, position.
  • a natural angle between two adjacent vertebral plates is replicated by fusing the two adjacent vertebrae.
  • the “natural angle” refers either to natural lordosis or to natural kyphosis.
  • the angle can be positive, negative or zero (i.e., when the opposing surfaces of the adjacent vertebrae are essntially coplanar).
  • a natural lordosis is replicated or restored.
  • natural lordosis refers to a natural angle between two adjacent vertebral plates within the lumbar or cervical spine segments wherein the distance between the anterior portions of the two adjacent vertebral plates is not smaller than the distance between the posterior portions of the two adjacent vertebral plates.
  • a natural kyphosis is replicated or restored.
  • natural kyphosis refers to a natural angle between two adjacent vertebral plates within the thoracic spine segment wherein the distance between the anterior portions of the two adjacent vertebral plates is not geater than the distance between the posterior portions of the two adjacent vertebral plates.
  • a fusion means maintains the separation between the vertebrae.
  • the fusion means at least partially restore the natural function of nucleus pulposis by permitting relative freedom of movement while substantially maintaining the separation between the vertebrae.
  • the components of the device comprise at least one member selected from the group consisting of a load-bearing component and an osteobiologic component. Preferably, both components are used.
  • load-bearing component includes osteobiologic component.
  • load-bearing component or material refers to any material capable of supporting vertebrae in distracted position.
  • the load-bearing component can include a hardenable material or a noncompressible fluid contained within an inflatable balloon.
  • strut refers to any part, portion or component of the device, including a flowable material, that either alone or in combination with other parts, portions or components of the device is capable of supporting vertebrae in distracted position.
  • a strut examples include a hardened flowable material, a balloon with rigid walls and an inflatable balloon or bag filled with a hardenable material or a noncompressible fluid.
  • the purpose of the strut is to bear the high spinal loads.
  • the strut can be used to increase the disc space height and/or at least partially restore or create natural curvature of the spinal region being fused. Increasing disc height is often critical for decompressing nerve roots and restoring or creating healthy spine curvature is important for preventing accelerated degeneration of adjacent intervertebral discs.
  • arcuate refers to a shape having curvature roughly corresponding to the perimeter of a vertebral endplate, but does not include enclosed rings or generally annular structures.
  • the “osteobiologic” component or material refers to any material that can induce and/or support existing or new bone growth.
  • the load-bearing material includes osteobiologic material.
  • a material comprising bone growth factors or mesynchemal stem cells is an osteobiologic component.
  • Osteobiologic component can further include either one or both an osteoinductive component and an osteoconductive component.
  • the “osteoinductive” component or material refers to any material that can induce bone growth.
  • osteoinductive components includes signal molecules required to induce the osteoprogenitor cells to form new bone.
  • osteoinductive components are bone morphogenetic proteins (BMP's), growth differentiation factors (GDF's) and transforming growth factors (TGF).
  • BMP's bone morphogenetic proteins
  • GDF's growth differentiation factors
  • TGF transforming growth factors
  • osteoconductive component or material refers to any material that can provide support for bone growth subsequent to induction.
  • osteoconductive components include natural collagen-based materials including bone, and synthetic porous resorbable polymers and ceramics.
  • the present invention relates to in situ formed intervertebral fusion devices.
  • the components of the in situ formed device can be delivered percutaneously (e.g., through a cannula having a diameter of no more than 5 mm, preferably no more than 2 mm).
  • the precursor components of the in-situ formed device can also be delivered in cannulae of much larger dimension (such as up to 18 mm, or through a Craig needle). More preferably, the components of the in-situ formed device are delivered into the disc space in the form of injectable compositions.
  • the term “in situ formed” refers to any material that is delivered into the disc space in a first form and takes on a different form after placed in the disc space.
  • “in situ formation” includes delivering a viscous fluid into the disc space and hardening that fluid.
  • “in situ formation” includes delivering discrete components into the disc space and bonding (preferably, heat bonding or by reaction) together those components.
  • “in situ formation” includes delivering discrete components into an opening in an inflatable device located in the disc space and preventing their escape from the inflatable device by closing off the opening of the inflatable device.
  • “in situ formation” includes delivering discrete components into the disc space and assembling together those components within the disc space.
  • In situ formation excludes simply packing particles such as autograft or allograft particles into the disc space, as well as simply delivering a gel into the disc space.
  • FIG. 1 the hypothetical strength profiles of a conventional resorbable implant (dotted line) and of the bone that replaces the implant (solid line) are provided.
  • the strength of the system is defined as the lesser of the strength of the resorbable implant and the strength of the healing bone. It then follows that between the time of the surgical procedure (T 0 ) and the time for complete bone healing to take place (T F ), the load applied to the system must never be above the strength of the system at point C (shown as S C ). It is known in the art that the maximum in vivo average daily living load on the human lumbar spine is approximately 4,000 N. Assuming that this is the maximum load to be experienced by the system, then the system strength should not fall below 4,000 N.
  • the strut can be made relatively strong (e.g., capable of supporting about 15 kN in axial compression), even when the load applied to the system is relatively high, the strength of the system will still be sufficient to support the disc space and fusion will occur. Once sufficient bone growth through the osteobiologic component occurs, the strut may degrade without endangering support of the disc space.
  • the strut supports the disc space while the osteobiologic composition grows bone.
  • the strut of the present invention acts in a manner similar to the cortical rim of a vertebral body. Desirable features for the load bearing composition of the strut are as follows:
  • c) degradation resistance e.g., capable of bearing at least 15 MPa, preferably at least 25 MPa for at least one year, preferably at least 18 months;
  • the present invention is an intervertebral spinal fusion device comprising a resorbable load-bearing material wherein the combination of the resorbable load-bearing material and the new bone growth provides a load-carrying capacity that is at least sufficient to support spinal load.
  • the load-bearing material includes or is supplemented by an osteobiologic component.
  • the present invention is a method of making an intervertebral fusion device comprising selecting a resorbable load-bearing material wherein the combination of the resorbable load-bearing material and the new bone growth provides a load-carrying capacity that is at least sufficient to support spinal load.
  • the strut should have a size sufficient to provide a footprint covering between about 3% and about 40% of the area of the corresponding vertebral endplate.
  • the strut foot covers between about 10% and about 30%, more preferably between about 10% and about 20% of the corresponding vertebral endplate.
  • the osteobiologic component contains at least one of a) a growth factor and b) an osteogenic component, e.g. a source of cells (such as stem cells), it is believed that the strut footprint can be in the range of about 10% to about 20% of the disc space. This is because it is believed that these additives sufficiently shorten the time to fusion so that the danger of strut subsidence is sufficiently low.
  • the osteobiologic component contains both a) a growth factor and b) stem cells, it is believed that the strut footprint can be in the range of about 5% to about 10% of the disc space.
  • osteobiologic component with both a) a growth factor and b) stem cells provides further desirable design options.
  • These additives may also reduce or eliminate the need for posterior or supplemental fixation.
  • posterior fixation is generally thought to be highly desirable to achieve a fusion success in the interbody space.
  • the provision of effective amounts of such additives can increase the speed for fusion so as to render superfluous the posterior or supplemental fixation, and patients would no longer need to endure a more invasive pedicle screw procedure to apply the stability needed for fusion.
  • the device can comprise a balloon of semicircular, circular, bilateral (comprising more than one balloon) and generally toroidal shape.
  • Preferred embodiments and positions of a device of the present invention on an endplate 8 of a vertebra 10 are shown in FIGS. 2 ( a ) through ( e ).
  • this shape allows the balloon 12 to essentially cover at least the anterior periphery 14 of the corresponding vertebral endplate 8 , and thereby bear a substantial portion of the spinal load.
  • This shape further allows the surgeon to first place the device in place and then fill the remaining portion of the disc space with, for example, an osteobiologic component.
  • the balloon 12 has a quasi-circular shape.
  • This device has the advantage of providing even more of a load-bearing footprint than the embodiment of FIG. 2( a ), and also substantially prevents unwanted leakage of the osetobiologic component during subsequent filling of an open cavity defined by an outer surface of the balloon.
  • the device comprises two balloons 12 that can be used to support the vertebral load.
  • the use of two balloons allows a surgeon to evenly support the load on each side of the endplate 8 .
  • the balloon 12 has a generally toroidal (“banana”) shape.
  • the banana shape allows the surgeon to put in place a single device preferably on the anterior half 14 of the disc space.
  • the strut has the footprint of a banana cage such as that described in Attorney Docket #DEP 5012, “Novel Banana Cage”, filed Dec. 31, 2002, U.S. Ser. No. 10/334,599, the specification of which is incorporated by reference in its entirety.
  • the strut 12 is introduced translaterally so as to form a single ramp stretching essentially transversely across the endplate 8 .
  • This design in advantageous when used in a posterolateral approach of surgery, as this approach takes advantage of the fact that the muscle planes in the vicinity of the approach allow the implant to be delivered in a less invasive manner.
  • the device 12 of the present invention has a substantially semiannular footprint.
  • the device 12 is placed on the anterior portion of the endplate 8 of a vertebra 10 so that height D of a anterior portion of the device is equal or greater than height h of a posterior portion of the device 12 .
  • the device 12 defines an internal radius r i , an external radius r e and thickness t.
  • r i is approximately about 22 mm
  • r e is approximately about 25 mm
  • t is approximately about 3 mm.
  • the height of the strut is at least 90%, and preferably at least equal to, the height of the natural disc space. This allows the surgeon to distract the disc space and restore at least a portion of the disc height. In some embodiments, the height of the strut is greater than that of the natural disc space.
  • the word “distraction” will refer to the separation of joint surfaces to a desired extent, without rupture of their binding ligaments and without displacement.
  • Distraction can be accomplished by any suitable means, for example mechanical or hydrostatic means.
  • Mechanical means can include, for instance, attaching hooks or jacks to the bony endplates and using those hooks or jacks to separate the bones.
  • the surgeon can employ external traction.
  • an in-situ foaming material is used as a distraction device.
  • Other means include, for example, hydrostatic means, e.g., by pressurized injection of the biomaterial itself.
  • the means used to accomplish distraction also serves the purpose of forming one or more barriers (e.g., balloons) for the flowable load bearing strut material.
  • the disc space can be distracted prior to and/or during either a discectomy itself and/or delivery of a flowable biomaterial.
  • a constricted disc space is generally on the order of 3 to 4 mm in height.
  • Suitable distraction means are capable of providing on the order of about 3 atmospheres to about 4 atmospheres, (or on the order of about 40 psi to about 60 psi) in order to distract that space to on the order of 8 to 12 mm in height.
  • the strut has a wedged shape so that the height of the anterior portion of the expanded device is greater than the height of the posterior portion of the expanded device. This allows the surgeon to restore lordosis when the interbody fusion device is used in either the lumbar or cervical regions of the spine.
  • the wedged shape produces an angle of between 5 and 20 degrees, more preferably between 5 and 15 degrees.
  • the strut has a wedged shape so that the height of the anterior portion of the expanded device is smaller than the height of the posterior portion of the expanded device. This allows the surgeon to restore kyphosis when the interbody fusion device is used in thoracic regions of the spine.
  • the wedged shape produces an angle of between 5 and 20 degrees, more preferably between 5 and 15 degrees.
  • the height of the medial portion of the strut is greater than the height of the lateral portion of the expanded device. This geometry more closely mimics the natural doming of the disc space.
  • a “custom” implant formed to the anatomy of the patient's endplates.
  • the provision of a conformable implant may provide a faster and more consistent fusion.
  • the annulus fibrosus can itself serve as a suitable mold for the delivery and solidification of either the flowable load-bearing material (in one embodiment) or the osteobiologic component (in another embodiment). Free injection may optimize the extent to which the injectable device conforms to the contour of the disc space, thereby enhancing resistance to retropulsion.
  • the interior surface of the annulus fibrosus can be treated or covered with a suitable material in order to enhance its integrity and use as a mold.
  • At least one of the flowable materials is delivered into an inflatable device (such as a balloon) previously placed in the disc space.
  • an inflatable device such as a balloon
  • the load bearing composition is delivered into an inflatable device (such as a balloon) previously placed in the disc space.
  • an inflatable device such as a balloon
  • a cannula 18 having an inner diameter of no more than 6 mm, is inserted into the disc space.
  • the inflatable device 12 is deployed through the exit opening of the cannula 18 and the flowable load bearing composition is introduced into the inflatable device at a pressure and volume suitable to expand the inflatable device and distract the disc space.
  • the fixed shape of the expanded device allows the surgeon to predetermine the shape of the flowable material and simply fill the device with the flowable material.
  • the device substantially prevents unwanted flow of the material.
  • the prevention of unwanted flow desirably prevents the material from damaging important surrounding structures such as the spinal cord, aorta and vena cava.
  • the inflatable device can be tailored to fill any portion of the disc space.
  • an inflatable balloon in a strut can assure that the opposing trends of degradation of bioabsorbable materials and new bone growth will result in fusion of the vertebrae in a position approximating the natural angle between two adjacent vertebrae.
  • the balloon is made of a resorbable, water-impermeable material, the balloon will effectively shield the load-bearing composition from water during the initial stages of fusion and so delay the onset of hydrolysis and degradation of the load-bearing material.
  • the balloon begins to degrade within about 1-2 months after fusion of the osteobiologic composition, thereby allowing the load-bearing material it contains to slowly degrade and grow bone.
  • the distraction of the disc space is accomplished by an inflatable, yet rigid, balloon or bladder.
  • the balloon can be delivered in deflated form to the interior of the annulus and there inflated in order to distract the disc space and provide a region for the delivery of biomaterial.
  • the balloon is preferably of sufficient strength and of suitable dimensions to distract the space to a desired extent and to maintain the space in distracted position for a period of time sufficient for the biomaterial to be delivered and, optionally, to harden.
  • One of the primary functions of the balloon is to influence or control the shape of the hardenable material, following injection therein.
  • the implantable balloon is not normally required to restrain pressure over an extended period of time.
  • a greater design flexibility may be permitted, as compared to conventional angioplasty or other dilatation balloons.
  • the balloon may be porous, either for drug delivery as has been discussed, or to permit osteoincorporation and/or bony ingrowth.
  • a method for fusing an intervertebral disc space comprising the steps of:
  • a method for fusing an intervertebral disc space comprising the steps of:
  • the space is distracted by the use of one or more suitable insertable or inflatable devices, e.g., in the form of inflatable balloons.
  • inflatable balloons When inflated, such balloons provide rigid walls (e.g., fiber supported) that are sufficiently strong to distract the space.
  • An inflatable device providing sufficient strength and dimensions can be prepared using conventional materials.
  • the uninflated balloon can be delivered to the center of the annular shell, and there inflated to expand the annular shell and in turn, distract the space.
  • the uninflated balloon can be delivered to the anterior rim of the annular shell, and there inflated to provide a cavity for the injection of the load bearing flowable material.
  • the load bearing composition is injected in an amount sufficient to distract the space.
  • the inflatable device can be delivered to the disc space by any suitable means, e.g., in deflated form retained within or upon the end of a rigid or semi-rigid rod.
  • a suitable gas e.g., nitrogen or carbon dioxide
  • the flowable load-bearing material can be delivered through the rod in order to inflate the balloon in situ, in a substantially radial or longitudinal direction.
  • beads of the load bearing strut material are simply packed into the balloon.
  • an inflatable device in one preferred balloon delivery system of the present invention there is provided an inflatable device, a motor drive unit, with a remote controller, associated tube sets, a nonscope inflow delivery cannula having independent fluid dynamics pressure and flow rate adjustments, attachments for the flush, vacuum, waste canister, and overflow jars.
  • Suitable materials for preparing balloons of the present invention may include those that are presently used for such purposes as balloon angioplasty. Suitable materials provide an optimal combination of such properties as compliance, biostability and biocompatability, and mechanical characteristics such as elasticity and strength. Balloons can be provided in any suitable form, including those having a plurality of layers and those having a plurality of compartments when expanded.
  • a useful balloon apparatus will include the balloon itself, together with a delivery catheter (optionally having a plurality of lumen extending longitudinally therewith), and fluid or gas pressure means.
  • suitable materials for making balloons include, but are not limited to, polyolefin copolymers, polyethylene, polycarbonate, polyethylene terephthalate and ether-ketone polymers such as poly(etheretherketone).
  • polyolefin copolymers polyethylene, polycarbonate, polyethylene terephthalate and ether-ketone polymers such as poly(etheretherketone).
  • Such polymeric materials can be used in either unsupported form, or in supported form, e.g., by the integration of DacronTM or other fibers.
  • the materials of construction of the balloon are resistant to softening or melting at a temperature of at least 80° C., preferably at least 100° C., more preferably at least 250° C.
  • the balloon may be made out of any of a wide variety of woven or nonwoven fibers, fabrics, metal mesh such as woven or braided wires, and carbon. Biocompatible fabrics or sheet material such as ePTFE and DacronTM may also be used.
  • Balloons can also take several forms, depending on the manner in which the biomaterial is to be delivered and cured.
  • a single, thin walled balloon can be used, for instance, to contact and form a barrier along the interior surface of the remaining annular material.
  • the flowable load bearing component can be delivered and solidified within the balloon to serve as a load bearing strut of the present invention.
  • the balloon is preferably of a type that will allow it to remain in position, without undue detrimental effect, between the annular material and the solidified load-bearing component.
  • a balloon can be provided that fills essentially only the central portion of the disc space.
  • the balloon can be, for instance, in the shape of a cylinder.
  • Such a balloon can be provided such that its upper and lower walls can be positioned to contact the opposing vertebral bodies, and its side walls will provide sufficient strength to cause, distraction of the space upon inflation.
  • the load-bearing component is delivered to the perimeter of the annular space, i.e., the space between the annular material and the balloon, and there solidified.
  • the balloon can be gradually deflated as additional biomaterial is inserted into the space. Then, once the load bearing material is stably positioned, the osteobiologic component is introduced into the balloon, thereby filling the balloon.
  • the balloon has metallic wires or other imageable means incorporated into it. Any material that can be seen under fluoroscopy would be acceptable. Potential materials include any metal, metal alloys, or ceramics that could be combined with a polymer. The material can be in the form of wires, a mesh, or particles incorporated into the balloon or on its surface.
  • the balloon has an inner surface that is chemically active so as to bond with the balloon filler as it polymerizes.
  • a chemical “bond” is said to exist between two atoms or groups of atoms when the forces acting between them are strong enough to lead to the formation of an aggregate with sufficient stability to be regarded as an independent species.
  • “chemically active” means capable of forming a chemical bond.
  • the surface is chemically modified by means such as plasma polymerization. In this case, the balloon is placed in a vacuum chamber and plasma containing a small molecule (an amine for example) is created. The balloon surface is bombarded by the small molecule and the small molecule is chemically attached to its surface.
  • the balloon's surface with its amine groups can then react with the polymer that is injected into the balloon (i.e., an epoxy), forming a device that would have greater fatigue properties since the “composite” of balloon and balloon filler are chemically bonded to one another.
  • the desired quantities of the load-bearing and osteobiologic components of the present invention are delivered by minimally invasive means to the prepared site. Prior to delivery, these components can be stored in suitable storage containers, e.g., sterile, teflon-lined metal canisters.
  • the flowable components can be delivered, as with a pump, from a storage canister to the delivery cannula on demand.
  • the components can be delivered in the form of a single composition, or can be delivered in the form of a plurality of components or ingredients.
  • the inflatable device can be filled with a viscous material that later solidifies to form the strut or osteobiologic component.
  • the viscous material can be a heated polymer (such as a composition containing polycaprolactone), or polymer precursor components (such as the photopolymerizable anhydrides disclosed by A. K. Burkoth, Biomaterials (2000) 21:2395-2404, the entire teachings of which are incorporated herein by reference).
  • a flowable load bearing composition such as polycaprolactone
  • heated to a temperature yielding a viscosity in the range of from about 100 to about 500 cps is injected into the balloon under pressure such as by using a pump and pressure within the range of from about 4 ATM to about 10 ATM or more depending upon viscosity, balloon strength and other design considerations.
  • the pump is run for a sufficient duration and under a sufficient pressure to ensure that the polycaprolactone wets all of the p-dioxanone fibers. This may range from about 10 minutes or more to about an hour, and, in one application where the pump was run at about 5 ATM pressure, requires at least about 1 hour.
  • Specific method parameters may be optimized depending upon the viscosity of the polycaprolactone, infusion pressure, infusion flow rate, density of the packed fibers, and other variables as will be apparent to those of skill in the art in view of the disclosure herein.
  • the inflatable device upon expansion, forms an upper surface having a first plurality of teeth projecting outwards from the upper surface. Upon expansion of the device, these teeth will project in the direction of the upper endplate and, upon complete expansion of the device, will engage the endplate to from a secure interlock with the endplate and resist retropulsion.
  • the teeth are made of a stiff resorbable material, such as polyetheretherketone (PEEK).
  • PEEK polyetheretherketone
  • the teeth have a height of between 0.5 and 1.5 mm, and have a triangular cross-section.
  • the inflatable device upon expansion, forms an upper surface formed of a material having a high coefficient of friction.
  • the high coefficient of friction of the upper and lower surfaces will case a drag upon any movement of the upper surface and therefore keep the device in place and resist retropulsion.
  • the upper and lower surfaces of the inflatable device are made from a material selected from a group consisting of polyether block copolymer (PEBAX), ABS (acrylonitrile butadiene styrene); ANS (acrylonitrile styrene); Delrin®; PVC (polyvinyl chloride); PEN (polyethylene napthalate); PBT (polybutylene terephthalate); polycarbonate; PEI (polyetherimide); PES (polyether sulfone); PET (polyethylene terephthalate); PETG (polyethylene terephthalate glycol), high and medium melt temperature: polyamides, aromatic polyamides, polyethers, polyesters, Hytrell®, polymethylmethacrylate, polyurethanes: copolymers, EVA (ethylene vinyl acetate) or ethylene vinyl alcohol; low, linear low, medium and high density polyethylenes, latex rubbers, FEP, TFE, PFA, polypropylene
  • PEBAX polyether
  • the vertebral endplates opposing the disc space are roughened.
  • the roughening provides hills and valleys into which a flowable polymer can flow and harden, thereby forming a mechanical interlock between the device and the bony surface and resisting retropulsion.
  • the roughening can be provided mechanically (as with a curette), or chemically (as by an acid), or by an energy-transmitting device (as with an ablation unit preferably assisted with hyperconductive fluid, such as hypertonic saline).
  • the flowable polymer forming a mechanical interlock can be a separate layer.
  • the flowable polymer can be a component of the strut.
  • the flowable polymer can be a component of the osteobiologic composition.
  • the strut portion of the device can have an outer layer of a scaffold material appropriately seeded with osteogenic factors and/or growth factors to produce quick bone ingrowth, thereby effectively locking the strut in place.
  • an outer layer of a scaffold material appropriately seeded with osteogenic factors and/or growth factors can also be applied to a balloon component of the osteobiologic component. The seeding again produces quick bone ingrowth, thereby effectively locking the osteobiologic component in place.
  • Balloons of the present invention can be made using materials and manufacturing techniques used for balloon angioplasty devices.
  • U.S. Pat. No. 5,807,327 by Green, the entire teachings of which are incorporated herein by reference, (hereinafter “Green”) discloses balloons that may be used in the present invention.
  • the materials disclosed by Green for the formation of the balloon include tough non-compliant layer materials (col. 8, lines 18-36) and high coefficient of friction layer materials (col. 8, lines 42-54).
  • the load-bearing component is delivered into the disc space through an inflatable balloon 12 , and the osteobiologic component 20 is freely injected.
  • This embodiment is desirable because the balloon 12 can act as a barrier to hydrolysis of the load-bearing component, thereby increasing the longevity of the load-bearing component.
  • the absence of the balloon covering the osteobiologic component may be desirable in instances in which it is desirable to immediately begin the bone growth process.
  • This embodiment may also be desirable in instances in which the load-bearing component comprises a cross-linkable composition, and the surgeon desires to provide a barrier between the patient's tissue and the precursors during the reaction of the precursors.
  • both the load bearing and the osteobiologic components are delivered into the disc space using a device comprising two separate inflatable balloons 12 .
  • This embodiment is desirable in instances in which both the annulus fibrosis has been functionally breached, and there is a concern that flowable materials would flow from the disc space and through the breach and into the remainder of the body.
  • the balloon containing the osteobiologic material be at least semi-permeable to nutrients and preferably resorbable.
  • semi-permeable refers to a material that is non-permeable to the flowable materials described above yet permeable to important water and nutrients to support bone growth therein.
  • Suitable semi-permeable materials include both porous and non-porous polymeric constructs such as films, fabrics (woven and non-woven) and foams.
  • both the load bearing and the osteobiologic components are delivered into the disc space through the same inflatable device.
  • FIGS. 7 ( a ) and ( b ) another embodiment of the device and method of the present inevtion is shown wherein the device comprises at least two inflatable balloons 12 .
  • the load-bearing component is delivered into the disc space through at least two inflatable balloons 12 and the osteobiologic component 20 is freely injected into the disk space using the space between the ballons.
  • the osteobiologic component is delivered into the disc space through an inflatable device, and the load-bearing component is freely injected.
  • the osteobiologic component comprises an in situ hardenable composition such as a calcium containing cement, or a crosslinkable polymer such as poly(propylene fumarate), polyanhydride, or polyoxaester, and the surgeon desires to cordon off the patient from the precursors during their reaction.
  • the balloon containing the osteobiologic material be at least semi-permeable to nutrients and preferably resorbable.
  • the load-bearing composition comprises growth factors and the surgeon desires to immediately begin the bone growth process in the load-bearing component.
  • the load-bearing component is delivered into the disc space through an inflatable device, and the osteobiologic component is freely injected.
  • This embodiment may also be desirable in instances in which the annulus fibrosis in essentially intact and the surgeon desires to immediately begin the bone growth process in the load-bearing component.
  • the inflatable device comprises a single peripheral wall having an upper and lower surface, upper and lower walls, and a cavity formed therebetween.
  • this shape of this embodiment is referred to as a “puck”.
  • the peripheral wall and upper and lower walls of the puck could be designed so as to be percutaneously deliverable through a cannula having an inside diameter of between 0.5 and 18 mm, preferably no more than 4 mm.
  • the peripheral wall of the puck is designed to be load bearing when the inflatable device is disposed in its inflated position.
  • the peripheral wall is made of a shape-memory metal, such as Nitinol, or a thin film alloy.
  • the periphery of the balloon is reinforced with fibers.
  • the peripheral wall comprises polymer fibers. These fibers can be made into a weave that is sufficiently flexible (in the longitudinal direction of the fiber) to pass through the cannula and expand into the expanded state. Typically, these fibers have high tensile strengths so that they can very efficiently accommodate the problematic hoop stresses that may be transferred from the osteobiologic component contained within the middle annulus of the balloon.
  • the fibers form X-shaped cross-hatching pattern.
  • the fibers form a continuous wave-like pattern having peaks and troughs, where said peaks and troughs approach upper and lower surfaces.
  • the walls of the device are reinforced by an internal frame forming a polygonal structure having sides on the upper, lower and peripheral surfaces.
  • the peripheral reinforcement is made of a resorbable polymer fiber.
  • the upper and lower walls of this puck embodiment are designed to initially accept and contain the osteobiologic component that is flowed into the puck cavity. Accordingly, the upper and lower walls should be at least semi-permeable so as to contain the osteobiologic component.
  • the upper and lower walls are made of a resorbable material that quickly resorbs, thereby exposing the contained osteobiologic material to blood flowing from the decorticated endplates.
  • this absorbable material has an elastomeric quality.
  • This elastomeric quality allows the resorbable upper and lower walls to be delivered through the cannula, and flatten upon device expansion.
  • this elastomeric polymer is selected from the materials disclosed in U.S. Pat. No. 6,113,624 by Bezwada, the entire teachings of which are incorporated herein by reference (hereinafter “Bezwada”).
  • this absorbable material is not elastomeric, and is preferably made of a thin film metal alloy or a braided metal alloy.
  • FIGS. 8 ( a ) and 8 ( b ) there is provided a device 30 of the present invention comprising an inflatable portion 32 that includes an arcuate inflatable balloon.
  • the inflatable portion 32 of the device 30 in its pre-deployed state, is conveniently repeatedly folded upon itself, thereby decreasing the size of the device 30 and allowing for minimally invasive insertion into the disc space.
  • the device 30 is preferably inserted in the sandwich orientation as shown in FIG. 8( a ) wherein the structural walls 34 are disposed essentially parallel to the vertebral endplates.
  • the sandwich orientation allows height H of the structural walls 34 to meet or exceed the disc space height, while the folded width W does not exceed the disc space height.
  • the structural walls 34 of this embodiment are preferably attached to the inflatable portion 32 by an adhesive.
  • the structural walls 34 should be designed so that the width W and the strength and modulus of the material of construction allow for both support of the disc space and bony fusion through the osteobiologic component.
  • the height H of the structural wall 34 is at least equal to the height of the natural disc space. This condition desirably restores the height of the disc space when the inflatable portion 32 is expanded. In some embodiments, the height H of the anterior portion of the wall 34 is greater than the height h of the posterior portion of the wall 34 . This condition desirably provides a lordotic effect upon expansion of the inflatable portion 32 .
  • the walls 34 are made of allograft bone, and preferably comprise cortical bone. In others, the walls are made of a synthetic resorbable polymeric material. In some embodiments, the walls may be sufficiently porous to provide an effective scaffold, thereby allowing bony fusion therethrough.
  • the wall component 34 of this embodiment is made of bone graft.
  • component 34 comprises additional inflatable portions. After insertion into the disc space, a load bearing composition may be flowed into the cavities of these additional inflatable portions, thereby expanding these additional inflatable portions and eventually producing the desired dimensions of the walls 34 .
  • each wall 34 is translaterally oriented in the expanded device.
  • a first wall supports essentially the anterior portion of the opposing cortical rims
  • the second wall supports essentially the posterior portion of the opposing cortical rims, so that one of these walls will essentially bear the entire load during flexion and the other wall will bear essentially the entire load during extension.
  • these walls have a length L corresponding to the anterior and posterior aspects of the cortical rim.
  • the inflatable portion 32 has upper and lower surfaces 36 and 38 for contacting the adjacent vertebral endplates, a peripheral side surface 40 connecting the upper and lower surfaces 36 and 38 , and an opening 42 in the peripheral side surface 40 .
  • the inflatable portion 32 is expanded and surfaces 36 , 38 and 40 are pushed apart sufficiently to form an internal cavity suitable for containing an osteobiologic component. Because the osteobiologic component retained within this cavity is preferably at least semipermeable in order to provide bony fusion, the upper and lower surfaces 36 and 38 of the inflatable portion 32 preferably do not act as barriers to bony fusion.
  • the upper and lower surfaces 36 and 38 are either porous (preferably, semipermeable) or quickly resorbable.
  • the upper and lower surfaces 36 and 38 are made of a material that resorbs within 7 days, preferably 3 days, preferably one day.
  • fast-resorbing materials include denatured collagen, polysaccharide-based materials such as starch and oxidized regenerated cellulose, and hydroxylated lactide-glycolide copolymers.
  • the opening in the side surface 40 is formed closely adjacent to the structural wall 34 , positioned anteriorly on a vertebral endplate.
  • the inflatable device 30 of this embodiment has a configuration designed to match the geometry of the disc space, and is selected from the group consisting of an anterior lumbar interbody fusion (ALIF) configuration, a posterior lumbar interbody fusion (PLIF) configuration, a vertebral body replacement (VBR) configuration, and an anterior cervical discectomy and fusion (ACDF) configuration.
  • ALIF anterior lumbar interbody fusion
  • PLIF posterior lumbar interbody fusion
  • VBR vertebral body replacement
  • ACDF anterior cervical discectomy and fusion
  • this embodiment of the present invention desirably minimizes the access window required for insertion of intervertebral devices.
  • the device 30 provides a stable environment for the muskuloskeletal growth factors to develop.
  • the device 60 comprises an outer side-wall component 62 , an inner side-wall component 64 , and a balloon 66 disposed between and attached to said inner and outer wall components.
  • the short cranial-caudal height of the inner and outer walls allows for the device to be inserted into the disc space without having to distract the disc space prior to insertion.
  • Subsequent filling of the balloon with an in-situ hardenable, load-bearing material causes the balloon to expand beyond the cranial and caudal margins of the sidewalls, thus providing the necessary distraction of the disc space.
  • the sidewalls prevent expansion of the balloon such that the thickness of the device is minimized upon inflation. Minimized wall thickness is important for ensuring maximum area for bone growth (fusion) between the adjacent vertebrae.
  • the footprints of the outer and inner side-wall components 62 and 64 represent substantially equal arcs of two concentric circumferences. This allows placing device 60 along the periphery of the anterior portion 14 of a vertebral endplate 8 and filling a cavity therewithin with a load bearing material.
  • the outer and inner walls 62 and 64 are made of a flexible plastic such as poly(ethyleneterephthalate), a superelastic metal such as Nitinol, or a flexible material/geometry combination, whereby each wall can be deformed into a relatively elongated shape for delivery to the disc space through a cannula 18 .
  • the sidewalls are sufficiently rigid to guide the device into the desired location in the disc space but sufficiently flexible to allow delivery through the cannula. Referring to FIG. 9( c ), during the insertion of the device 60 , upon release from the cannula 18 , components 62 and 64 can then take on the desired arcuate shape. Referring to FIG.
  • the device 60 is expanded by injecting a load-bearing component, an osteobiologic component or a combination thereof into a cavity formed by the components 62 , 64 , and 66 .
  • a load-bearing component an osteobiologic component or a combination thereof
  • Any suitable injection means can be used, for example, a syringe pump 70 .
  • components 62 and 64 ensure that the cavity produced between side walls 62 , 64 can be filled so that the device 60 distracts the disc space and can also create a wedge shape for creating or restoring healthy curvature of the spine.
  • FIGS. 10 ( a ) and ( b ) An alternative embodiment of inflatable device of the present invention is shown in FIGS. 10 ( a ) and ( b ).
  • Device 260 comprises an upper wall component 266 and a lower wall component 268 joined by an inflatable balloon 270 .
  • the footprints of the upper and lower wall components 266 and 268 represent substantially equal arcs of two concentric circumferences. This allows placing device 260 along the periphery of the anterior portion 14 of a vertebral endplate 8 and filling a cavity therewithin with a load bearing material.
  • the upper and lower wall components 266 and 268 are made of a superelastic material such as Nitinol, or a flexible material/geometry combination, whereby each wall can be deformed into a relatively elongated shape for delivery to the disc space through a cannula 18 .
  • device 260 is similar to device 60 . Insertion of device 260 can be accomplished in a manner depicted in FIG. 9( c ). Upon release from cannula 18 , components 266 and 268 can then take on the desired arcuate shape. Subsequent to insertion, device 260 is inflated by injecting a load-bearing component, an osteobiologic component or a combination thereof into balloon 270 . Any suitable injection means can be used, for example a syringe pump.
  • balloon 270 is semi-permeable.
  • balloon 270 is made of a material that quickly resorbs, thereby exposing the contained osteobiologic material to blood flowing from the decorticated endplates.
  • the strut is deliverable through a cannula having an inside diameter of between 3 mm and 18 mm, preferably between 4 mm and 12 mm, more preferably between 5 mm and 10 mm.
  • the strut is preferably deliverable through a cannula having an inside diameter of between 0.5 mm and 6 mm, preferably between 1 mm and 4 mm, more preferably between 2 mm and 3 mm.
  • the upper and lower surfaces of the upper and lower walls, respectively, have teeth that prevent excessive movement of the strut after implantation.
  • the device 80 comprises four rail components 82 wherein the footprints of the rail components 82 represent substantially equal arcs of two concentric circumferences. Components 82 are joined by an inflatable balloon 84 such that the device can be inserted in a collapsed configuration as shown in FIG. 11( b ) and then expanded as shown in FIG. 11( a ) once filled with a load-bearing material to increase disc height and provide thickness for load bearing support.
  • device 80 is shown in FIGS. 12 ( a ) and ( b ).
  • device 80 is delivered in a generally diamond-shaped configuration, shown in plan view on FIG. 12( a ) and in lateral view in FIG. 12( b ).
  • the upper and lower rails 82 will cause slight subsidence of the vertebral body endplates, thus providing stability of the implanted device.
  • FIGS. 13 ( a ) through ( d ) a preferred embodiment of the method of the present invention is shown.
  • a cannula 18 is inserted into an intervertebral space.
  • an inflatable balloon 12 of a generally toroidal shape is inserted through the cannula 18 into the intervertebral space.
  • the balloon 12 is expanded by directing a load-bearing component into said balloon.
  • osteobiologic component 20 is injected into the open cavity defined by the outer surface of the balloon 12 .
  • the osteobiologic component comprises a water-soluble component.
  • the water-soluble component is dissolved, thus forming a porous matrix shown in FIG. 13( d ).
  • the load-bearing component is delivered through a balloon, and the osteogenic component is provided in a hydrogel phase of the osteobiologic component.
  • suitable hydrogels are provided hereinbelow.
  • the strut is formed by bonding together two bondable components.
  • the bondable materials are selected from the group consisting of heat bondable materials such as polycaprolactone, and polymerizable materials such as poly(propylene fumarate) and polyoxaesters including photo-curable materials such as polyanhydrides.
  • load-bearing materials in the form of beads is delivered into the inflatable device and packed into the device so as to create a stable strut having an open interstitial porosity.
  • the beads may be packed without subsequent stabilization other than closing off the opening of the balloon.
  • the beads are preferably polyarylether ketone (PAEK), more preferably polyetherether ketone (PEEK) with chopped carbon fiber.
  • a bonding material may be subsequently flowed into the interstitial porosity to further stabilize the packed beads.
  • this bonding material comprises an aliphatic polyester such as polycaprolactone (PCL).
  • PCL polycaprolactone
  • the bonding material may be resorbable and may include osteogenic additives such as growth factors and stem cells.
  • the beads of the load-bearing material are made of a heat-bondable material, such as polycaprolactone.
  • heat may be delivered into the packing and soften the contacting surfaces of the beads. Upon subsequent cool down to body temperature, the contacting surfaces solidify to further stabilize the packed structure.
  • the heat is provided exogenously. In other embodiments, the heat is provided by the patient's body heat ( ⁇ 37° C.).
  • another embodiment of the device of the present invention 300 comprises at least two bondable components 310 and 320 , that are delivered into the disc space in unassembled form, placed closely adjacent one another, and then bonded together, preferably by heat bonding.
  • device 300 comprises first and second portions 310 and 320 .
  • First portion 310 has a lower bearing wall 312 , upper angled wall 314 , and a leading wall 316 and a trailing wall 318 .
  • Second portion 320 has an upper bearing wall 322 , lower angled wall 324 and a leading wall 326 and a trailing wall 328 .
  • the combined height of the assembled portion H exceeds that of the disc space.
  • the angled walls form the same angle so that the leading edge of the second portion can be ramped up the angled wall of the first portion.
  • the first portion 310 is placed in the disc space. Because the height of the first portion is less than the disc space, the first portion 310 is easily positionable anywhere within the disc space.
  • the second portion 320 is introduced into the disc space and ramped up the angled wall of the first portion. Corresponding rails and groove are provided on the angled walls of the first and second portion so as to guide the second portion along the an long wall of the first portion (see below). Because the second portion only contacts the lower portions of the first portion, the upper wall 322 of the second portion 320 does not touch the adjacent endplate during ramping and so the ramping is easy. Only when the ramping is essentially complete does the upper wall of the second portion contact the adjacent upper endplate.
  • the overall height of the ramp H is slightly greater than that of the disc space, so that distraction is achieved when the leading edge of the second portion reaches the leading edge of the first portion.
  • a cross-section of the device of FIG. 14( a ) is shown, taken along arrows B.
  • angled wall 314 of first portion 310 includes a grove 330
  • angled wall 324 of second portion 320 includes a ridge 332 , designed to fit into a slide against grove 330 .
  • ridge 332 further includes a metal filament 334 .
  • the rail and groove feature of the ramps has a Morse taper so as to lock the ramp in its assembled form when the leading edge of the second portion reaches the leading edge of the first portion.
  • the ramp of this embodiment is not flowed into the disc space, and the heating is very localized, extremely strong, high temperature materials such as PEEK may be used as the material of construction.
  • the ramp is made of a high temperature resorbable material.
  • the high temperature absorbable material is amorphous and has a glass transition temperature of above 100° C.
  • the amorphous absorbable is PLA.
  • the high temperature absorbable material is crystalline and has a melting point of above 100° C.
  • the crystalline absorbable is p-dioxanone.
  • a guidewire is guided through the center of the ramp guide.
  • the guidewire would allow the ramps to be inserted over the guidewire.
  • the guidewire could be remotely steered into place via IGS or equivalent, and then the ramps could be passed over the guidewire into place.
  • the ramps could be semi-rigid which would allow them to follow the guidewire through the soft tissue, over the wire.
  • an “I”-Beam ramp cage is provided.
  • the ramp cage discussed above could incorporate or mate with modular tops and bottoms. These tops and bottoms would have tracks, which would locate on guides fixed to the ramps (or the guides could be on the modular top, and tracks on the ramps) which would aid insertion and ensure the ramps were connected to these modular tops and bottoms.
  • the surfaces of the modular tops and bottoms would go between the ramps and the vertebral bodies such that when assembled, a cross-section of the ramp/top/bottom assembly would resemble an “I”-Beam.
  • the ramps and modular tops could be shaped in several configurations, inserted assembled, or assembled within the disk space.
  • a ribbon-shaped ramp having a longitudinal through-hole.
  • a threaded rod is inserted through the middle of the ribbon so that, as the threaded rod is turned, the ribbon would “accordion” itself, increasing its height within the disk space.
  • This “accordion”-ing could be achieved by other methods, such as a spring, a cable, etc.
  • FIG. 15 one embodiment of a method of use of device 300 shown in FIGS. 14 ( a )-( d ) is depicted.
  • the first and second ramp portions 310 and 320 are introduced translaterally so as to form a single ramp stretching essentially transversely across the disc space.
  • This design in advantageous when used in a posterolateral approach, as this approach takes advantage of the fact that the muscle planes in the vicinity of the approach allow the implant to be delivered in a less invasive manner.
  • the medial portion of the ramp has a height that is higher than the lateral portions. This feature provides the doming that is advantageous in interbody fusions
  • FIG. 16 another embodiment of a method of use of device 300 , shown in FIGS. 14 ( a )-( c ) is depicted.
  • the ramp of the present invention may be advantageously used in a PLIF procedure.
  • two ramps may be constructed in-situ so as to form bilateral struts similar to the Steffee struts.
  • an intervertebral fusion device comprising a strut comprising:
  • a) a first component comprising:
  • the struts are completely dense. This feature maximizes the strength of the strut, and so is desirable for the load bearing.
  • the strut has openings sized to permit bony fusion therethrough.
  • the upper and lower walls have openings designed to promote bony fusion from the upper endplate to the lower endplate.
  • the sidewalls of the strut also have such openings.
  • the openings have a diameter of at least 2 mm. In other embodiments, the openings are in the range of from 50-500 um, more preferably between 100 and 300 um, preferably between 100 and 250 um. These preferred opening sizes are believed to be more conductive to bone growth.
  • second phase refers to an additive that enhances the performance of the material, for example carbon fibers enhance the strength of the material and calcium phosphate particulates enhance the osteoconductivity of the material.
  • aqueous phase refers to a component of the material capable of maintaining cell viability, e.g. an alginate hydrogel.
  • load-bearing components that satisfy the above Table include at least one compound selected from the group consisting of poly(lactic acid), poly(glycolic acid), p-dioxanone fibers, polyarylethyl, polymethylmethacrylate, polyurethane, amino-acid-derived polycarbonate, polycaprolactone, aliphatic polyesters, calcium phosphate, unsaturated linear polyesters, vinyl pyrrolidone and polypropylene fumarate diacrylate or mixtures thereof.
  • osteobiologic components that satisfy the above Table include at least one member selected from the group consisting of mesenchymal stem cells, a growth factor, cancellous bone chips, hydroxyapatite, tri-calcium phosphate, polylactic acid, polyglycolic acid, polygalactic acid, polycaprolactone, polyethylene oxide, polypropylene oxide, polysulfone, polyethylene, polypropylene, hyaluronic acid, bioglass, gelatin, collagen and a polymeric fiber.
  • some matrix components may be used in some instances as the matrix for the load bearing component and in other instances as the matrix for the osteobiologic component.
  • polycaprolactone may be used in conjunction with p-dioxanone reinforcing fibers as a matrix for a load bearing component, and may also be used in conjunction with polylactic acid and hydroxyapatite as a matrix for an osteobiologic component.
  • the term “hardenable” refers to a material that can be delivered through a cannula into the disc space in a viscous form.
  • material that can be delivered through a cannula having at least about 6 mm internal diameter.
  • a cannula has a diameter of no more than about 6 mm.
  • the flowable load-bearing composition and osteobiologic component of the present invention are flowable, meaning they are of sufficient viscosity to allow their delivery through a cannula of on the order of about 2 mm to about 6 mm inner diameter, and preferably of about 3 mm to about 5 mm inner diameter.
  • Such biomaterials are also hardenable, meaning that they can solidify, in situ, at the tissue site, in order to retain a desired position and configuration.
  • the hardenable material is simply a material (such as a low temperature polymer) having a melting point (for crystalline materials) or a glass transition temperature (for amorphous materials) less than 100° C., and is solid a body temperature (37° C.).
  • these low temperature materials are simply heated to the point where they are viscous and flowable and then injected into the disc space. The subsequent cooling of the viscous material to body temperature then solidifies them. Because these materials do not need to react in-situ, they are desirable for their relative inertness. Accordingly, in some embodiments, they may be freely injected into the disc space without a protective balloon.
  • the hardenable material comprises a cross-linkable component (or “cross-linking agent”).
  • cross-linkable component or “cross-linking agent”.
  • the load-bearing component comprises a cross-linking agent.
  • the cross-linking agent be delivered into the disc space through a balloon so that the balloon may protect the surrounding tissue from the reactive components during the reaction.
  • the load-bearing component comprises a cross-linking agent.
  • the osteobiologic component comprises a cross-linking agent.
  • the hardenable material comprises a polymer and a cross-link agent. In some embodiments, the hardenable material may further comprise a monomer. In some embodiments, the hardenable material may further comprise an initiator. In some embodiments, the hardenable material may further comprise an accelerant.
  • the cross-linking component is made from a two-part composition comprising a monomer and a crosslinking agent.
  • the cross-linked composition is flowable at a temperature of between 37° C. and 40° C.
  • the cross-linkable component is resorbable.
  • a resorbable material loses 50% of its initial strength within no more than two years after implantation.
  • Providing a resorbable cross-linkable component is desirable because it not only provides the high initial strength required for supporting the disc space in an intervertebral fusion application, but also allows for the eventual replacement by bone fusion.
  • the resorbable cross-linkable component comprises those cross-linkable components disclosed by Wise in U.S. Pat. No. 6,071,982, the entire teachings of which are incorporated herein by reference.
  • the cross-linkable component is UV curable.
  • UV curable cross-linkable components are disclosed in Biomaterials (2000), 21:2395-2404 and by Shastri in U.S. Pat. No. 5,837,752, the entire teachings of which are incorporated herein by reference.
  • the cross-linkable component is water-curable.
  • the resulting body is typically somewhat weak, and so it is preferred that the water-curable cross-linkable compound be used as a matrix for the osteobiologic component.
  • the strut is made of a non-resorbable material. Since the non-resorbable material does not degrade over time, the use of the non-resorbable material provides the surgeon with a measure of safety and prevents collapse of the disc space in the event the osetobiologic composition does not produce a fusion.
  • the non-resorbable material is a polymer.
  • the selection of a polymer allows the material to be flowed into place.
  • the load bearing polymer is a polyarylethyl ketone (PAEK). More preferably, the PAEK is selected from the group consisting of polyetherether ketone PEEK, polyether ketone ketone PEKK and polyether ketone PEK. In preferred embodiments, the PAEK is polyetherether ketone.
  • PAEK-type polymers have a very high melting point (e.g., 250° C.) and so are not amenable to flow at desirable temperatures. Accordingly, embodiments of the present invention using PAEK as the load bearing composition would typically deliver PAEK in a solid form, such as in bead form or as pre-constructed components, and then assemble and heat bond the components in the disc space under very high temperatures (e.g., 250° C.). These high temperatures would likely require the use of a highly insulated expanded device.
  • the strut is a composite comprising fiber, preferably carbon fiber.
  • Composite struts comprising carbon fiber are advantageous in that they typically have a strength and stiffness that is superior to neat polymer materials such as a polyarylethyl ketone PAEK.
  • the fiber preferably, carbon fiber, comprises between 1 percent by volume and 60 percent by volume (vol %). More preferably, the fiber comprises between 10 vol % and 50 vol % of the composite.
  • the polymer and carbon fibers are homogeneously mixed.
  • the composite strut is a laminate.
  • the carbon fiber is present as chopped state. Preferably, the chopped carbon fibers have a median length of between 1 mm and 12 mm, more preferably between 4.5 mm and 7.5 mm. In some embodiments, the carbon fiber is present as continuous strands.
  • the composite strut comprises:
  • polyarylethyl ketone PAEK is selected from the group consisting of polyetherether ketone PEEK, polyether ketone ketone PEKK and polyether ketone PEK.
  • the composite strut consists essentially of PAEK and carbon fiber. More preferably, the composite strut comprises about 60 wt % to about 80 wt % PAEK and about 20 wt % to about 40 wt % carbon fiber. Still more preferably the composite strut comprises about 65 wt % to about 75 wt % PAEK and about 25 wt % to about 35 wt % carbon fiber.
  • the physical requirements of the flowable load bearing component will depend upon the length and diameter of the arc as well as the physical requirements imposed by the implantation site.
  • certain load-bearing compositions may or may not exhibit sufficient physical properties.
  • Physical properties of the load bearing components can also be modified through the addition of any of a variety of reinforcements, such as carbon fibers, KevlarTM or Titanium Rods, woven or laser etched metallic tubular stents, or other strength enhancers as will be understood in the art.
  • Certain composite materials such as carbon fibers embedded in a bonding agent such as a polycaprolactone are believed to be particularly useful in forming the load bearing component of the present invention.
  • graphite (carbon fibers) having a diameter within the range of from about 0.003 to about 0.007 inches is provided in bundles (tows) composed of from about 3,000 to about 12,000 fibers.
  • One typical fiber useful for this purpose is manufactured by Hexcel Carbon Fibers, Salt Lake City, Utah, Part No. HS/CP-5000/IM7-GP 12K.
  • the Tow tensile strength is in the range of from about 5,000 to about 7,000 Mpa.
  • Tow tensile modulus is within the range of from about 250 to about 350 Gpa.
  • carbon fibers having within the range of from about 15 to about 45 degrees of braids are utilized within the inflatable device to reinforce the load bearing material.
  • the braid may be in the form of a plain weave, and may be obtained, for example, from Composite Structures Technology (Tehachapi, Calif.).
  • a 0.5 inch diameter of 45 degrees braided carbon fiber sleeve is positioned within the center of the balloon. This braided sleeve conforms dimensionally to the inside diameter of the balloon.
  • a 0.3 inch diameter braided carbon sleeve may also be positioned concentrically within the balloon, within the outer braided carbon fiber sleeve. Unidirectional fibers are thereafter introduced inside of the ID of the inner braided carbon sleeve.
  • Unidirectional fibers are also introduced into the annular gap between the two braided sleeves.
  • the volume of the fiber per volume of balloon is generally within the range of from about 40% to about 55%.
  • the flowable load bearing material of the present invention having a viscosity within the range of from about 100 cps to about 500 cps is injected under 10 atmospheres pressure into the balloon.
  • the use of braided sleeves will produce higher structural resistance to sheer stress as a result of torsional loads, plus the ability to distribute unidirectional fibers in a homogenous manner within the balloon at all times.
  • the polymer comprises polymethylmethacrylate (PMMA).
  • the matrix comprises a radio-opaque agent.
  • DMDMA diurethane dimethacrylate
  • TEGDMA triethylene glycol dimethacrylate
  • the load bearing composition comprises polyurethane.
  • the polyurethane materials disclosed in U.S. Pat. No. 6,306,177 by Felt hereinafter “Felt”
  • Felt the specification of which is incorporated by reference to the extent it is not inconsistent with the remainder of the specification, is selected.
  • Polyurethanes can be tailored to have optimal stiffness by adjusting the ratio of soft segment to hard segment ratio in the polymer. Furthermore, polyurethanes can be prepared as two-part systems that will cure upon mixing. Preferred polyurethanes, e.g., thermoplastic polyurethanes (“TPU”), are typically prepared using three reactants: an isocyanate, a long-chain macrodiol, and a short-chain diol extender. The isocyanate and long-chain diol form a “soft” segment, while the isocyanate and short-chain diol form a “hard” segment. The hard segments form ordered domains held together by hydrogen bonding. These domains act as cross-links to the linear chains, making the material similar to a cross-linked rubber. It is the interaction of soft and hard segments that determines and provides the polymer with rubber-like properties.
  • TPU thermoplastic polyurethanes
  • the strut comprises a photocurable material.
  • the material comprises organophosphorous compounds. These compounds are advantageous because the resulting product is calcium phosphate based, and so is both biocompatible and resorbable.
  • the strut has a resorbable matrix material.
  • a resorbable matrix material is desirable because it is eventually resorbed by the body, and may eventually be replaced by bone.
  • the resorbable strut is a high temperature material.
  • a high temperature material flows above 100° C.
  • the high temperature absorbable material enters the disc space as a plurality of components in a solid form. The components are then contacted in the disc space, and heat is applied to bond the components without deforming the assembled shape.
  • the load bearing composition includes a matrix comprising an amino-acid derived polycarbonate.
  • the osteobiologic component comprises a matrix comprising a biodegradable polyurethane.
  • the osteobiologic component comprises a matrix comprising an amorphous polymer and has a glass transition temperature of below 100° C.
  • the amorphous absorbable is D,L-polylactic acid (PLA).
  • a poly(lactide-co-lysine) functionalized with peptide containing the arginine-glycine-aspartate (RGD) sequence was prepared by removal of the benzyoxycarbonyl protecting group on the lysyl residue and peptide coupling.
  • the peptide concentration was found to be approximately 3.1 mmol/g, which could be translated into a peptide surface density of 310 fmol/cm 2 .
  • a surface density of as low as 1 fmol/cm 2 of an RGD peptide has been previously determined to promote cell adhesion to an otherwise nonadherent surface (Massia and Hubbell, 1991). Therefore, by carefully processing the copolymer, biodegradable films with cell adhering properties can be prepared from the copolymer of lactide and lysine.
  • polylactic acid has also been synthesized as an acrylic macromonomer and subsequently copolymerized with polar acrylic monomers (e.g., 2-hydroxyethylmethacrylate) (Barakat et al., 1996). These polymers were studied as amphiphilic graft copolymers for drug delivery purposes. The surface properties of these polymers may be controlled by the ratio of the polylactic acid graft length and copolymer content, and can be potentially used to control the drug release profile and biodistribution. Other examples of this approach include grafting polylactic acid blocks to geraniol and pregnenolone (Kricheldorf and Kreiser-Saunders, 1996).
  • the high temperature resorbable material is semi-crystalline and has a melting point of above 100° C.
  • the semi-crystalline absorbable is selected from the group consisting of p-dioxanone, L-polylactic acid and poly(glycolic acid) (PGA), and mixtures thereof.
  • the strut comprises at last 90 wt % of an aliphatic polyster.
  • the aliphatic polyester is polycaprolactone (“PCL”).
  • Polycaprolactone is a linear polyester formed through the ring opening of the monomer epsilon-caprolactone.
  • Polycaprolactone is a semi-crystalline thermoplastic resin, which can be readily molded at moderate temperatures to yield tough translucent products. Its crystalline melting point is about 60° C., which represents a theoretical upper temperature limit of use for the present invention. Above its melting point the material is characterized by a high degree of conformability and workability.
  • polymers such as poly(dodecene-1) and transpolyisoprene are also useful in this invention. These polymers are characterized by being crystalline at room temperature, non-crystalline at about 70° C. and having a relatively rapid rate of crystallization when cooled to body temperature. These polymers do not crystallize like simple compounds so that there is a reasonable time lag after the polymer reaches body temperature before crystallization is complete. This permits sufficient time for the flowable composition to be positioned in the disc space while the polymer is still pliable.
  • an absorbable component comprising a polymer formed from aliphatic lactone monomers selected from the group consisting of p-dioxanone, trimethylene carbonate, ⁇ -caprolactone, glycolide, lactide (l, d, dl, meso), delta-valerolactone, beta-butyrolactone, epsilon-decalactone, 2,5-diketomorpholine, pivalolactone, alpha, alpha-diethylpropiolactone, ethylene carbonate, ethylene oxalate, 3-methyl-1,4-dioxane-2,5-dione, 3,3-diethyl-1,4-dioxan-2,5-dione, gamma-butyrolactone, 1,4-dioxepan-2-one, 1,5-dioxepan-2-one, 1,4-dioxan-2-one, 6,8-dioxabi
  • the strut comprises a load bearing composition consisting essentially of polycaprolactone.
  • the compressive strength of essentially solid polycaprolactone is about 15 MPa, and its compressive modulus is about 0.5 GPa.
  • the higher molecular weight polycaprolactones are preferred, as they tend to have a higher strength and degrade more slowly.
  • the molecular weight of the polycaprolactone is at least 30,000 Daltons. More preferably, the molecular weight of the polycaprolactone is at least 40,000 Daltons.
  • the strut comprises a load bearing composition of cross-linked polycaprolactone.
  • the cross-linking of the polycaprolactone should enhance its strength.
  • the load bearing composition comprises a self-interpenetrating network (S-IPN) comprising a network of host polycaprolactone and cross-linked polycaprolactone.
  • S-IPN self-interpenetrating network
  • the compressive strength of the S-IPN of polycaprolactone may be about 45 MPa, and its compressive modulus may be about 1.5 GPa.
  • the polycaprolactone is heat treated to enhance its crystallinity, and thereby even further enhance its resistance to degradation.
  • the above described polymers of the present invention may be liquid or low melting temperature, low molecular weight polymers, with or without photocurable groups.
  • the liquid or low melting polymers are of sufficiently low molecular weight, having an inherent viscosity of about 0.05 to about 0.5 dL/g, to yield materials which can easily flow, with or without heat being applied, through a small diameter delivery device such as a syringe or cannula, with or without mechanical assistance, a caulking gun, a soft-sided tube, and the like.
  • the aliphatic polyesters useful in the practice of the present invention will typically be synthesized by conventional techniques using conventional processes.
  • the lactone monomers are polymerized in the presence of an organometallic catalyst and an initiator at elevated temperatures.
  • the organometallic catalyst is preferably tin based, e.g., stannous octoate, and is present in the monomer mixture at a molar ratio of monomer to catalyst ranging from about 10,000/1 to about 100,000/1.
  • the initiator is typically an alkanol, a glycol, a hydroxyacid, or an amine, and is present in the monomer mixture at a molar ratio of monomer to initiator ranging from about 100/1 to about 5000/1.
  • the polymerization is typically carried out at a temperature range from about 80° C. to about 220° C., preferably from about 160° C. to about 200° C., until the desired molecular weight and viscosity are achieved.
  • the homopolymers and copolymers of aliphatic polyesters will typically have a weight average molecular weight of about 5,000 grams per mole to about 200,000 grams per mole, and more preferably about 10,000 grams per mole to about 100,000 grams per mole. Polymers of these molecular weights exhibit inherent viscosities between about 0.05 to about 3.0 deciliters per gram (dL/g), and more preferably about 0.1 to about 2.5 dL/g as measured in a 0.1 g/dL solution of hexafluoroisopropanol (HFIP) or chloroform at 25° C.
  • HFIP hexafluoroisopropanol
  • Suitable lactone monomers used in the matrices of the present invention may be selected from the group consisting of glycolide, lactide (l, d, dl, meso), p-dioxanone, trimethylene carbonate, ⁇ -caprolactone, delta-valerolactone, beta-butyrolactone, epsilon-decalactone, 2,5-diketomorpholine, pivalolactone, alpha, alpha-diethylpropiolactone, ethylene carbonate, ethylene oxalate, 3-methyl-1,4-dioxane-2,5-dione, 3,3-diethyl-1,4-dioxan-2,5-dione, gamma-butyrolactone, 1,4-dioxepan-2-one, 1,5-dioxepan-2-one, 1,4-dioxan-2-one, 6,8-dioxabicycloctane-7-one
  • the aliphatic polyesters used in the matrices of the present invention consist of homopolymers of poly( ⁇ -caprolactone), poly(p-dioxanone), or poly(trimethylene carbonate) or copolymers or mixtures thereof, or copolyesters of p-dioxanone or trimethylene carbonate and glycolide or lactide or mixtures thereof, and in particular, copolymers of p-dioxanone/glycolide, p-dioxanone/lactide, trimethylene carbonate/glycolide and trimethylene carbonate/lactide, or copolyesters of .epsilon.-caprolactone and glycolide or mixtures thereof, or mixtures of homopolymers of ⁇ -caprolactone and lactide.
  • a biocompatible, non-absorbable, flowable polymer whose melting point is from about 45° C. to about 75° C. and which is a rigid solid at body temperatures below about 42° C. is placed in a standard Toomeytype disposable syringe with a 35 mm diameter and appropriate capacity of about 50-100 milliliters.
  • the filled syringe is placed in a peel-apart package for sterile delivery and sterilized with cobalt radiation or heat, the former being preferred.
  • the polymer can be placed in a squeeze bottle of suitable capacity and having a slit orifice.
  • the strut comprises at least 90 wt % calcium phosphate.
  • the compressive strength of hydroxyapatite is about 65 MPa and the tensile strength of hydroxyapatite is about 10.6 MPa. The present inventors believe that these values should satisfy typical strut load requirements.
  • the matrix is made of a cross-linkable compound.
  • cross-linkable compounds cross-link in-situ and provide higher compressive strengths (typically on the order of 20-120 MPa) than heat-flowable polymers (typically on the order of 1-20 MPa.
  • the cross-linkable compound comprises an unsaturated linear polyester.
  • the unsaturated linear polyester comprises a fumarate double bond, and more preferably comprises polypropylene fumarate.
  • the cross-linkable compound is cross-linked by a monomer, preferably a vinyl monomer, more preferably vinyl pyrrolidone.
  • the links produced by the cross-linking agent are biodegradable. Preferred embodiments thereof include polypropylene fumarat-diacrylate.
  • the cross-linking reaction is aided by an initiator.
  • the initiator is benzoyl peroxide.
  • light is used as the photoinitiator.
  • the cross-linking reaction is aided by an accelerant.
  • the accelerant is N,N-Dimethyl-p-toluidine.
  • the terminal functional groups affect the strength and degradation resistance of the cross-linked matrix.
  • the cross-linked compound is terminated by a terminal group selected from the group consisting of diepoxide, or diacryal functional groups.
  • the terminal groups are diepoxide functional groups. These terminal functional groups were shown to be more resistant to degradation than divinyl terminated polypropylene fumarat (Domb 1996).
  • a porogen such as NaCl or a foaming agent is added to the cross-linkable composition.
  • the porogen is water soluble, more preferably it is a water soluble salt or sucrose.
  • a calcium phosphate based compound such as hydroxyapatite or tricalcium phosphate, is added to the cross-linkable composition.
  • hydroxyapatite or tricalcium phosphate are desirable because they can provide an osteoconductive pathway for bone growth, they can neutralize any acid produced from hydrolysis of the polymer matrix, and provide reinforcement.
  • the calcium phosphate is nano high aspect hydroxyapatite.
  • the strut of the present invention comprises a load bearing composition
  • a load bearing composition comprising a fumarate-based polymer (such as polypropylene fumarate) cross-linked with a cross-linking agent containing a polupropylene fumarate-unit, such as polypropylene fumarate-diacrylate.
  • a fumarate-based polymer such as polypropylene fumarate
  • a cross-linking agent containing a polupropylene fumarate-unit such as polypropylene fumarate-diacrylate.
  • Exemplary compositions are disclosed in Timmer, Biomaterials (2003) 24:571-577, the entire teachings of which are incorporated herein by reference. These compositions are characterized by a high initial compressive strength (about 10-30 MPa) that typically increases over the first 12 weeks, high resistance to hydrolytic degradation (about 20-50 at 52 weeks), and an acceptable modulus for use as a strut (0.5-1.2 GPa).
  • the polypropylene fumarate: polypropylene fumarate-diacrylate double bond ratio is between about 0.1 and about 3. In more preferred embodiments, the polypropylene fumarate-diacrylate double bond ratio is between about 0.25 and about 1.5.
  • the load bearing composition comprising polypropylene fumarate cross-linked by polypropylene fumarate-diacrylate further comprises tricalcium phosphate (TCP), preferably in an amount of between about 0.1 wt % and about 1 wt %.
  • TCP tricalcium phosphate
  • This composition is characterized by a high initial compressive strength (about 30 MPa) that typically increases over the first 12 weeks (to about 45 MPa), a high resistance to hydrolytic degradation (about 45 MPa at 52 weeks), and an acceptable modulus for use as a strut (1.2 GPa at 52 weeks).
  • the strut or load bearing composition comprises two cross-linkable polymer compositions.
  • each of the cross-linkable compositions cross-links with itself, but not with the other cross-linked polymer.
  • the result thereof is a matrix comprising two cross-linked polymers. These are called “interpenetrating networks” (“IPN”).
  • IPN interpenetrating networks
  • the strut or load bearing composition comprises a first cross-linkable polymer composition and a second non-cross linkable polymer composition.
  • first cross-linkable compound cross-links with itself, while the second polymer remains unaffected.
  • second polymer remains unaffected.
  • the result thereof is a matrix comprising a first cross linked polymer and a second non-cross linked polymers.
  • the S-IPNs comprise a first biodegradable polymer capable of producing acidic products upon hydrolytic degradation; a second biodegradable polymer, which, preferably via crosslinking, provides a biopolymer scaffolding or internal reinforcement; and optionally a buffering compound that buffers the acidic products within a desired pH range.
  • the second biodegradable polymer comprises polypropylene fumarate (PPF) which is cross-linked, desirably by a vinyl monomer such as vinyl pyrrolidone (VP) to form the biopolymer scaffolding which provides the semi-IPN with the requisite dimensional and geometric stability.
  • PPF polypropylene fumarate
  • VP vinyl monomer
  • a beneficial end use of this material is in the form of internal fixation devices (IFDs) such as bone supports, plates, and pins, and/or bone cements for bone repair which are formed from the semi-IPN alloy disclosed herein.
  • IFDs internal fixation devices
  • the S-IPN comprises a bone cement containing a biodegradable polymeric semi-IPN alloy comprising a first biodegradable polymer (such as PLGA) capable of producing acidic products upon hydrolytic degradation; and a second biodegradable polymer (such as polypropylene fumarate), which provides a biopolymer scaffolding or internal reinforcement, wherein the second biodegradable polymer is polymerized in vivo to provide a hardened, semi-IPN alloy bone cement.
  • a biodegradable polymeric semi-IPN alloy comprising a first biodegradable polymer (such as PLGA) capable of producing acidic products upon hydrolytic degradation; and a second biodegradable polymer (such as polypropylene fumarate), which provides a biopolymer scaffolding or internal reinforcement, wherein the second biodegradable polymer is polymerized in vivo to provide a hardened, semi-IPN alloy bone cement.
  • Both the bone cement and dimensionally and geometrically stable IFDs of the disclosure of the invention may advantageously also contain other agents such as bone repair proteins (BRPs) and antibiotics, to, e.g., actively promote bone growth and prevent infection while the bone cement or IFD is in place.
  • BRPs bone repair proteins
  • antibiotics to, e.g., actively promote bone growth and prevent infection while the bone cement or IFD is in place.
  • S-IPNs of the present invention include at least two components.
  • the first component is a linear, hydrophobic biodegradable polymer, preferably a homopolymer or copolymer which includes hydroxy acid and/or anhydride linkages or a linear, non-biodegradable hydrophilic polymer, preferably polyethylene oxide or polyethylene glycol.
  • the second component is one or more crosslinkable monomers or macromers. At least one of the monomers or macromers includes a degradable linkage, preferably an anhydride linkage.
  • the linear polymer preferably constituted between 10 and 90% by weight of the composition, more preferably between 30 and 70% of the composition.
  • the crosslinked polymer preferably constitutes between about 30 and 70% by weight of the semi-interpenetrating network composition, more preferably, between 40 and 60 percent of the composition, with the balance being excipients, therapeutic agents, and other components.
  • the compositions form semi-interpenetrating polymer networks when these components are mixed, and the crosslinkable component is crosslinked.
  • Semi-interpenetrating networks are defined as compositions that include two independent components, where one component is a crosslinked polymer and the other component is a non-crosslinked polymer.
  • These S-IPN compositions can have a viscosity before crosslinking anywhere between a viscous liquid suitable for injection to a moldable, paste-like putty.
  • the viscosity can be adjusted by adding reactive diluents and/or by adding appropriate solvents.
  • the compositions are solid semi-interpenetrating networks, which are capable of supporting, bone growth and repair.
  • Linear polymers are defined as homopolymers or block copolymers that are not crosslinked. Hydrophobic polymers are well known to those of skill in the art. Biodegradable polymers are those that have a half-life under physiological conditions of between about two hours and one year, preferably less than six months, more preferably, less than three months. Examples of suitable biodegradable polymers include polyanhydrides, polyorthoesters, polyhydroxy acids, polydioxanones, polycarbonates, and polyaminocarbonates. Preferred polymers are polyhydroxy acids and polyanhydrides. Polyanhydrides are the most preferred polymers.
  • Linear, hydrophilic polymers are well known to those of skill in the art.
  • Non-biodegradable polymers are those that have a half-life longer than approximately one year under physiological conditions.
  • suitable hydrophilic non-biodegradable polymers include poly(ethylene glycol), poly(ethylene oxide), partially or fully hydrolyzed poly(vinyl alcohol), poly(ethylene oxide)-co-poly(propylene oxide) block copolymers (poloxamers and meroxapols) and poloxamines.
  • Preferred polymers are poly(ethylene glycol), poloxamines, poloxamers and meroxapols. Poly(ethylene glycol) is the most preferred polymer.
  • the composition includes one or more monomers or macromers. However, at least one of the monomers or macromers includes an anhydride linkage.
  • Other monomers or macromers that can be used include biocompatible monomers and macromers, which include at least one free-radical polymerizable group.
  • polymers including ethylenically unsaturated groups, which can be photochemically crosslinked may be used, as disclosed in WO 93/17669 by the Board of Regents, University of Texas System, the entire teachings of which are incorporated by reference.
  • the cross-linking polymer of the S-IPN comprises a fumarate, preferably polypropylene fumarate.
  • the non-cross-linkable polymer of an S-IPN may also be referred to as a host polymer.
  • the host polymer for the S-IPN is selected from the group consisting of polylactic acid, polyglycolic acid, and their copolymers.
  • the cross-linkable compound in the S-IPN is cross-linked by N-vinyl pyrrolidone, polyethylene glycol dimethacrylate (PEG-DMA), ethylene dimethacrylate (EDMA), 2-hydroxyethyl methacrylate (HEMA) or methylmethacrylate (MMA).
  • PEG-DMA polyethylene glycol dimethacrylate
  • EDMA ethylene dimethacrylate
  • HEMA 2-hydroxyethyl methacrylate
  • MMA methylmethacrylate
  • a photopolymerized anhydride is used as the matrix material. These materials are characterized as being strong (compressive strength 30-40 MPa), and relatively stiff (tensile modulus of about 600 MPA to about 1400 MPa).
  • A. K. Burkoth, Biomaterials (2000) 21:2395-2404 discloses a number of photopolymerizable anhydrides as suitable for orthopaedic use.
  • the repeating unit of these anhydrides comprises a pair of diacid molecules linked by anhydride bonds that are susceptible to hydrolysis. Because the diacid molecules are hydrophobic, there is a limited diffusion of water into the polymer, and so the polymer is subject only to surface degradation (not bulk degradation). This is advantageous because the strength of the polymer will essentially correspond to the mass of the polymer.
  • the photopolymerized anhydride is selected from the group consisting of polymers of methacrylated sebacic acid (MSA), methacrylated 1,6-bis(p-carboxyphenoxy) hexane (MCPH), 1,3-bis(p-carboxyphenoxy) propane (CPP), methacrylated cholesterol (MC), methacrylated stearic acid (MstA) and blends and copolymers therefrom.
  • MSA methacrylated sebacic acid
  • MCPH methacrylated 1,6-bis(p-carboxyphenoxy) hexane
  • CPP 1,3-bis(p-carboxyphenoxy) propane
  • MC methacrylated cholesterol
  • MstA methacrylated stearic acid
  • the photopolymerization is carried out by adapting a light source to the distal end of the delivery cannula that enters the disc space.
  • a photo-optic cable is used to transmit light energy into the precursor components that have been deposited in the disc space.
  • light is transmitted through the skin (i.e, transcutaneously) or through the annulus fibrosus.
  • a photobleaching initiating system is used.
  • a linear polyanhydride is first dissolved in a monomer, and then photopolymerized to form a S-IPN of a photopolymerized anhydride.
  • the load bearing composition of the present invention comprises a S-IPN comprising a photopolymerized anhydride.
  • PCPH poly (1,6-bis (p-carboxyphenoxy)hexane
  • Photoinitiators that generate an active species on exposure to UV light are well known to those of skill in the art. Active species can also be formed in a relatively mild manner from photon absorption of certain dyes and chemical compounds.
  • These groups can be polymerized using photoinitiators that generate active species upon exposure to UV light, or, preferably, using long-wavelength ultraviolet light (LWUV) or visible light.
  • LWUV and visible light are preferred because they cause less damage to tissue and other biological materials than UV light.
  • Useful photoinitiators are those, which can be used to initiate polymerization of the macromers without cytotoxicity and within a short time frame, minutes at most and most preferably seconds.
  • Exposure of dyes and co-catalysts such as amines to visible or LWUV light can generate active species. Light absorption by the dye causes the dye to assume a triplet state, and the triplet state subsequently reacts with the amine to form an active species, which initiates polymerization. Polymerization can be initiated by irradiation with light at a wavelength of between about 200-700 nm, most preferably in the long wavelength ultraviolet range or visible range, 320 nm or higher, and most preferably between about 365 and 514 nm.
  • dyes can be used for photopolymerization. Suitable dyes are well known to those of skill in the art. Preferred dyes include erythrosin, phloxime, rose bengal, thonine, camphorquinone, ethyl eosin, eosin, methylene blue, riboflavin, 2,2-dimethyl-2-phenylacetophenone, 2-methoxy-2-phenylacetophenone, 2,2-dimethoxy-2-phenyl acetophenone, other acetophenone derivatives, and camphorquinone.
  • Suitable cocatalysts include amines such as N-methyl diethanolamine, N,N-dimethyl benzylamine, triethanol amine, triethylamine, dibenzyl amine, N-benzylethanolamine, N-isopropyl benzylamine. Triethanolamine is a preferred cocatalyst.
  • Photopolymerization of these polymer solutions is based on the discovery that combinations of polymers and photoinitiators (in a concentration not toxic to the cells, less than 0.1% by weight, more preferably between 0.05 and 0.01% by weight percent initiator) will crosslink upon exposure to light equivalent to between one and three mWatts/cm.sup.2 applied to the skin of nude mice.
  • the matrix comprises a co-polymer having shape memory qualities.
  • the shape memory polymer comprises a first crosslinkable monomer and a second monomer having shape memory qualities.
  • the linear polyester has a molecular weight of at least 10,000.
  • the first monomer is a linear polyester.
  • the second shape memory monomer is n-butyl acrylate.
  • cross-linking is induced without an initiator.
  • the shape memory polymer comprises between about 70 wt % and about 90 wt % of the first crosslinkable monomer and between 10 and 30 wt % of the a second monomer having shape memory qualities.
  • the shape memory polymer matrix has a compressive strength of at least 15 MPa. This would make it a suitable candidate as a load bearing composition in a strut of the present invention.
  • polylactic acid is the first linear polyester. It is believed that polylactic acid would provide a strong, stiffer matrix, more suitable for use as a load bearing composition in the strut of the present invention.
  • a second part comprising a second bioerodible scaffolding polymer, which upon crosslinking provides a biopolymeric scaffolding or internal reinforcement for the S-IPN, and a crosslinking agent for the second bioerodible scaffolding polymer.
  • the S-IPN comprises:
  • a) a first part comprising a first bioerodible polymer capable of producing acidic products upon hydrolytic degradation, a crosslinking initiator, and preferably, a therapeutically effective amount of a biologically active or therapeutic agent and a combination of citric acid and sodium bicarbonate; and
  • a second part comprising a second bioerodible scaffolding polymer, which upon crosslinking provides a biopolymeric scaffolding or internal reinforcement for the S-IPN, and a crosslinking agent for said second bioerodible scaffolding polymer.
  • the resorbable materials are believed to have only moderate strength and stiffness. Therefore, it may be desirable to increase the strength and stiffness of the strut's matrix material by adding reinforcements to the matrix.
  • the fibers can be made of non-resorbable materials (such as chopped carbon fibers), preferably the reinforcements are made of materials that are also resorbable.
  • the fiber comprises carbon fiber.
  • carbon fiber comprises between about 1 vol % and about 60 vol % (more preferably, between about 10 vol % and about 50 vol %) of the load bearing composition.
  • the polymer and carbon fibers are homogeneously mixed.
  • the material is a laminate.
  • the carbon fiber is present as chopped state.
  • the chopped carbon fibers have a median length of between 1 mm and 12 mm, more preferably between about 4.5 mm and about 7.5 mm.
  • the carbon fiber is present as continuous strands.
  • Biodegradable polymers are known, commercially available, or can be synthesized into fibers using known and published methods.
  • Examples of polymers useful in the present invention include poly(L-lactic acid), poly(D,L-lactic acid), poly(D L-lactic-co-glycolic acid), poly(glycolic acid), poly(epsilon-caprolactone), polyorthoesters, and polyanhydrides. These polymers may be obtained in or prepared to the molecular weights and molecular weight distribution needed for service as either the matrix polymer or the pore-forming polymer by processes known in the art.
  • Preferred polymers are poly(alpha-hydroxy esters). Suitable solvent systems are known in the art and are published in standard textbooks and publications.
  • p-dioxanone fibers are used as the reinforcing phase of the strut. These fibers are advantageous because the high melting point of p-dioxanone resists any thermal degradation of the fibers during injection into the disc space.
  • the strut compositions comprise aliphatic polyesters reinforced with p-dioxanone fibers.
  • those compositions disclosed in U.S. Pat. No. 6,147,135 by Yuan hereinafter “Yuan”
  • Yuan the specification of which is incorporated herein by reference in its entirety, are selected.
  • both the osetobiologic composition and the strut are bioresorbable.
  • the selection of a bioresorbable strut is advantageous because it reduces the amount of foreign materials left in the body.
  • load-bearing component is used alone.
  • the strut material can also include bone growth materials, such as growth factors and stem cells that promote bone growth upon eventual resorption of the resorbable strut.
  • bone growth materials such as growth factors and stem cells that promote bone growth upon eventual resorption of the resorbable strut.
  • stem cells since the stem cells must typically be housed in an aqueous phase (such as a hydrogel), the inclusion of stem cells likely requires the introduction of a porosity into the strut that may significantly degrade the strength of the strut. Since the primary purpose of the strut is to support the disc space while the osteogeneic composition promotes fusion, adding stem cells to the strut composition may not be fully desirable in all circumstances. Therefore, in preferred embodiments, only growth factors are added to the strut composition.
  • the growth factors are first provided in an aqueous solution and particles of the resorbable strut material are added to the solution. The growth factors cling to the outer surface of the particles. Next, the growth factor-laden particles are separated from the growth factor solution. Next, the growth factor-laden particles are added to the viscous resorbable material.
  • the device of the present invention has at least one of the following characteristics: Desired Range Typical Range Specification of Values of Values Ultimate Load >5 kN 5-25 kN in Axial Compression Stiffness >5 kN/mm 5-25 kN/mm in Axial Compression Ultimate Load >2 kN 2-6 kN in Compression Shear Stiffness >3 kN/mm 3-9 kN/mm in Compression Shear Ultimate Load >5 N-m 5-20 N-m in Static Torsion Stiffness >>1 kN/mm 1-4 kN/mm in Compression Shear
  • the material comprising the strut of the present invention has at least one of the following intrinsic properties: More Intrinsic Property Preferred Value Preferred Value Compression Strength >11 MPa >25 MPa Fracture Strength >20 MPa >40 MPa Compression Modulus 0.1-10 GPa 0.5-2 GPa
  • the strut device of the present invention has at least one of the following mechanical performance characteristics: Mechanical Property Preferred Value More Preferred Value Static Compressive Load >2 kN >4 kN Cyclic Comp. Load (10 6 cycles) >1 kN >2 kN
  • FIGS. 2 ( f ) and ( g ) One example of this embodiment is shown in FIGS. 2 ( f ) and ( g ).
  • the arcuate shape has a thickness (t) of 3 mm, inner radius (r i ) of 22 mm, an outer radius (r o ) of 25 mm and an average height if 15 mm.
  • this device is produced from a photopolymerized polyanhydride with an intrinsic compressive strength of 30 MPa and compressive modulus of 1 GPa, the static compressive load required to fail the device is 6.6 kN and the compressive stiffness is 15 kN/mm.
  • the novel struts of the present invention can be used with conventional osteobiologic materials, such as platelet-rich plasma (PRP), allograft particles (such as demineralized bone matrix (DBM) and cancellous chips) and autograft.
  • PRP platelet-rich plasma
  • allograft particles such as demineralized bone matrix (DBM) and cancellous chips
  • autograft autograft
  • the osteobiologic component of the present invention acts in a manner similar to the cancellous core of a vertebral body. Desirable features for the osteobiologic composition of the strut are as follows:
  • the in-situ formed osteobiologic composition comprises:
  • a matrix material preferably, a polymer flowable at between 40° C. and 80° C.; a linear anhydride, or a fumarate,
  • osteogenenic component preferably, mesenchymal stem cells present in a concentrated amount
  • an osteoinductive factors preferably, a bone morphogenetic protein
  • the matrix is a resorbable composition that resorbs within a 2-4 month time period after in-situ formation and comprises:
  • a polymer phase that flows or softens at a temperature of between 40° C. and 80° C. (more preferably, comprising an aliphatic polyester such as polycaprolactone) and is preferably present in an amount of between 50 vol % and 70 vol % of the osteobiologic composition, and
  • an osteoconductive calcium phosphate phase (more preferably hydroxyapatite) preferably present in an amount of between 10 vol % and 30 vol % of the osteobiologic composition.
  • a reinforcing phase (preferably, resorbable polymeric chopped fiber) is also preferably present in an amount of between about 10 vol % and about 30 vol % of the osteobiologic composition.
  • the osteogenic component comprises an aqueous phase (preferably a hydrogel phase) having viable osteoprogenitor cells (preferably mesenchymal stem cells) present therein in a concentrated amount.
  • the aqueous phase is present as an interconnected phase throughout the osetobiologic composition, and is present in an amount of between about 25 vol % and about 35 vol % of the osteobiologic composition and has an average diameter of between 100 and 250 ⁇ m.
  • the osteoinductive factor is selected from the group consisting of a bone morphogenetic protein and a transforming growth factor. More preferably, the osteoinductive factor is a bone morphogenetic protein.
  • the bone morphogenetic protein may be present in any phase of the osteobiologic composition. When immediate delivery of the bone morphogenetic protein is desirable, the bone morphogenetic protein is present in the hydrogel phase. When intermediate delivery of the bone morphogenetic protein is desirable, the bone morphogenetic protein is present in the polymer phase. When long term delivery of the bone morphogenetic protein is desirable, the bone morphogenetic protein is present in the ceramic phase. It is preferable to have at least twice the autologous level of bone morphogenetic protein, and more preferably, at least 10 times the autologous level of bone morphogenetic protein.
  • the matrix comprises a material having a melting point between about 42° C. and about 95° C., (preferably between about 42° C. and about 90° C.) which allows it to be flowed into the disc space without causing tissue necrosis, and then in-situ solidified to provide the needed structural support.
  • the scaffold material further comprises a porogen that allows it to be made into a porous scaffold by conventional leaching techniques.
  • growth factors and osteoprogenitor cells such as mesenchymnal stem cells can be flowed through the open porosity of the scaffold to induce bone growth throughout the scaffold.
  • mesenchymnal stem cells are isolated from a bone marrow aspirate taken from the patient and incorporated into bioabsorbable particles capable of maintaining cell viability, such as hydrogels.
  • the hydrogels will absorb quickly such that the cells will be released to form bone.
  • the particulate are then mixed with a scaffold material in a first liquid form that will solidify upon implantation.
  • the scaffold material resorbs slowly such that bone can be formed throughout the porosity before the scaffold degrades away.
  • Preferred scaffold materials are polymers that can be dissolved in a cell-friendly solvent such as dimethyl sulfoxide (DMSO), which will leach out once implanted, causing the polymer to precipitate out of solution and create a solid scaffold.
  • a growth/nutritive factor cocktail for inducing the osteoprogenitor cells to form bone and continue to support the bone formation process is incorporated into the cell-seeded hydrogel as well as the scaffold material. Following disc space preparation the system is injected to the disc space and no other surgical steps are required.
  • an in-situ formed (and preferably injectable) intervertebral fusion device comprising:
  • Porous scaffolds that can form upon injection through a minimally invasive surgical procedure can be made of a material selected from the group consisting of crosslinked natural and synthetic polymers, low melting point polymers, polymers dissolved in biocompatible solvents, and setting ceramics.
  • Porous scaffolds suitable for use in the present invention are disclosed in U.S. Pat. Nos. 6,280,474 and 6,264,695 (swellable polymers), U.S. Pat. No. 5,888,220 (polycaprolactone/polyurethane), U.S. Pat. No. 6,224,894 (absorbable polyoxaester hydrogels) and U.S. Pat. No. 6,071,982, the entire teachings of the forgoing U.S. patents are incorporated herein by reference.
  • the resorbable polymers, calcium phosphates and reinforcing phases disclosed above in the description of the strut may be used to form the preferred matrix.
  • the matrix is substantially weaker (owing to the presence of either open porosity or an interconnected hydrogel phase) than the strut, and hydrolyzes quicker.
  • the matrix has a first absorbable phase of about 1 weight percent to about 99 weight percent of any of the aliphatic homopolyesters of ⁇ -caprolactone, p-dioxanone, or trimethylene carbonate or copolymers or mixtures thereof, with the remaining resorbable phase comprising a bone osteoconductive or osteoinductive calcium containing, non-fibrous, powdered compound, preferably a calcium phosphate such as hydroxyapatite, tri- or tetra-calcium phosphate, or a bioactive glass, or mixtures thereof.
  • a bone osteoconductive or osteoinductive calcium containing, non-fibrous, powdered compound preferably a calcium phosphate such as hydroxyapatite, tri- or tetra-calcium phosphate, or a bioactive glass, or mixtures thereof.
  • the matrix has a first absorbable phase of about 1 weight percent to about 99 weight percent of aliphatic copolyesters of p-dioxanone or trimethylene carbonate, and glycolide or lactide or mixtures thereof, and in particular, copolymers of p-dioxanone/glycolide, p-dioxanone/lactide, trimethylene carbonate/glycolide and trimethylene carbonate/lactide, with a remaining resorbable phase comprising a bone osteoconductive or osteoinductive calcium containing, non-fibrous, powdered compound, preferably a calcium phosphate such as hydroxyapatite, tri- or tetra-calcium phosphate, or a bioactive glass, or mixtures thereof.
  • a bone osteoconductive or osteoinductive calcium containing, non-fibrous, powdered compound preferably a calcium phosphate such as hydroxyapatite, tri- or tetra-calcium phosphate, or a bioactive glass,
  • the matrix has a first absorbable phase of about 1 weight percent to about 99 weight percent of aliphatic copolyesters of ⁇ -caprolactone and glycolide or mixtures thereof, or mixtures of homopolymers of ⁇ -caprolactone and lactide, with a remaining resorbable phase comprising a bone osteoconductive or osteoinductive calcium containing, non-fibrous, powdered compound, preferably a calcium phosphate such as hydroxyapatite, tri- or tetra-calcium phosphate, or a bioactive glass, or mixtures thereof.
  • a bone osteoconductive or osteoinductive calcium containing, non-fibrous, powdered compound preferably a calcium phosphate such as hydroxyapatite, tri- or tetra-calcium phosphate, or a bioactive glass, or mixtures thereof.
  • the above-noted matrices will contain sufficient amounts of the absorbable polymer phase and sufficient amounts of the resorbable second bone regenerating phase to effectively function as bone cements or bone substitutes.
  • the composites will contain about 1 to about 99 weight percent of polymer phase, and more preferably about 5 to about 95 weight percent.
  • the composites will typically contain about 1 to about 99 weight percent of the bone regenerating phase, and more preferably about 5 to about 95 weight percent.
  • the relative amounts of the first absorbable, polymeric phase to the second resorbable phase in the above-noted matrices will depend upon various parameters including, inter alia, the levels of strength, stiffness, and other physical and thermal properties, absorption and resorption rates, setting and hardening rates, deliverability, etc., which are required.
  • the desired properties of the composites of the present invention and their level of requirement will depend upon the body structure area where the bone cement or substitute is needed. Accordingly, the composites of the present invention will typically contain about 1 weight percent to about 99 weight percent, and more preferably about 5 weight percent to about 95 weight percent of aliphatic polyester homo- or co-polymers, or blends thereof.
  • a further aspect of the present invention is a process by which the matrix component of the osteobiologic composition is prepared.
  • the matrix can be prepared by a one-step or a two-step process in which a bone regenerating material is mixed in the reaction vessel with a just-formed polymer (one-step process), or mixed with a pre-formed polymer in a separate vessel (two-step process).
  • the composites of the present invention can be manufactured in the following two-step process.
  • the preformed polymers and bone regenerating materials are individually charged into a conventional mixing vessel having a conventional mixing device mounted therein such as an impeller.
  • the polymers and bone substitutes are mixed at a temperature of about 150° C. to about 220° C., more preferably about 160° C. to about 200° C., for about 5 to about 90 minutes, more preferably for about 10 to about 45 minutes, until a uniformly dispersed composite is obtained.
  • the composite is further processed by removing it from the mixing device, cooling to room temperature, grinding, and drying under pressures below atmospheric at elevated temperatures for a period of time.
  • the composites can be prepared by a one-step process by charging the bone regenerating material to a reaction vessel which contains the just-formed polymers. Then, the polymers and bone substitutes are mixed at a temperature of about 150° C. to about 220° C., more preferably about 160° C. to about 200° C., for about 5 to about 90 minutes, more preferably for about 10 to about 45 minutes, until a uniformly dispersed composite is obtained. Then, the composite is further processed by removing it from the mixing vessel, cooling to room temperature, grinding, and drying under pressures below atmospheric at elevated temperatures for a period of time.
  • the matrix of the present invention includes a bone implant material, which can be readily molded at a selected temperature at or below about 60° C.
  • the material is formed as a cohesive mixture of hard filler particles and a binder composed of a biocompatible, biodegradable thermoplastic polymer having fluid-flow properties at the selected temperature at or below about 60° C.
  • any hard biocompatible filler particles including autogenous bone chips, can be used in this invention.
  • hydroxyapatite is a preferred filler for its permanance and biological profile.
  • Tricalcium phosphate and glass granules may also be used alone or in combination with hydroxyapatite, particularly if some degree of resorption is desired in the filler.
  • the binder preferably ranges in fluid-flow properties (flowability) between a highly viscous fluid and a putty-like semi-solid, at the selected temperature. With too low a binder viscosity, the implant material suffers the same problems seen in loose-particle implants: poor shape retention, once molded, and poor cohesiveness, leading to exfoliation of particles before or during the tissue ingrowth period.
  • the polymer includes polylactic acid having a molecular weight between about 400 and about 5,000 daltons.
  • the binder preferably constitutes no more than about one-third of the total solid volume of the material, leaving void space in the material, which can accommodate tissue ingrowth.
  • the minimum amount of binder is that necessary to give easy formability and provide sufficient particle cohesion and shape retention during the period of tissue ingrowth.
  • polylactic acid having progressively greater molecular weights between about 2,000 and about 5,000 daltons were prepared and tested for binder characteristics when formulated with hydroxyapatite particles. Above about 2,000 daltons, the implant material was quite hard and difficult to mold by hand at 40° C., and at 5,000 daltons, temperatures up to about 60° C. were required to achieve moldability.
  • the binder from above is mixed with hydroxyapatite particles, and the components are thoroughly blended.
  • the material contains some void space, to allow tissue ingrowth independent of polymer breakdown. Since the void space of a mass of spherical particles is about one-third that of the particle mass, the implant material preferably contains less than about one-third by volume of binder.
  • the minimum amount of binder needed to produce good particle cohesiveness typically between about 5% and 20% of the total solid volume of the material, is added.
  • implant material containing 80% hydroxyapatite particles (average particle size of about 650 microns), and 20% of polylactic acid polymer having average polymer molecular weights of about 1,100 daltons was prepared.
  • the material was easily moldable by hand at 50° C., and showed good cohesiveness and shape retention at 37° C.
  • a moldable hydroxyapatite bone-implant material As described above, implant material having a range of molding temperatures and biodegradability can be provided, by adjusting the composition and amount of binder in the material. Material having a relatively high molding temperature, e.g., between about 40° C. to about 60° C., is generally preferred where the implant needs to be in a relatively rigid condition during the process of tissue ingrowth, for example, to prevent significant shape deformation. Here the material is applied and shaped to the bone site in a heated state; after cooling, it assumes the desired rigid condition.
  • the material can be formulated with thermoplastic polymer binders of various composition and molecular weights, to achieve a selected molding temperature, rigidity in the bone site, and rate of binder breakdown. By varying the relative proportions of binder and particles, selected changes in the void space and cohesiveness of the material are possible.
  • Matrix scaffold polymers can also be produced by first dissolving the polymer in a biocompatible, water-soluble solvent, injecting the material into the disc space, and then allowing the solvent to leach out of the polymer into the body, thereby causing the polymer to solidify in vivo.
  • Suitable polymers compatible with such solvents include, but are not limited to, poly(lactic acid), poly(glycolic acid) and copolymers therefrom.
  • Suitable biocompatible, water-soluble solvents include dimethylsulfoxide (DMSO).
  • DMSO dimethylsulfoxide
  • the volume ratio of polymer to solvent is at least 1:5, more preferably at least 1:2.
  • injectable ceramics can also serve as components in the matrix of the osteobiologic component.
  • Preferred injectable, resorbable ceramics are amorphous calcium phosphates or hydroxyapatites. (See U.S. Pat. Nos. 6,214,368 and 6,331,312, the entire teachings of which are incorporated herein by reference.)
  • porosity is produced in the matrix to produce a porous scaffold material.
  • an osteogenic component such as mesenchymnal stem cells
  • an osteoinductive component such as bone morphogenetic protein
  • Providing porosity in-situ allows the matrix of the osteobiologic composition to comprise materials such as polymers that flow at temperatures only well above body temperature. For example, many polymers such as polycaprolactone flow at about 60° C., a temperature that may well destroy the viability of mesenchymnal stem cells contained within the flowable polymer.
  • polymeric materials that become flowable above 45° C. are first made flowable by raising their temperature to at least 45° C., the flowable polymer is then injected into the disc space, the in-situ formed material is then made porous, and porous material is then injected with mesenchymnal stem cells.
  • in-situ porosity is accomplished by first delivering the matrix material into the disc space as beads, then tightly packing the beads within the disc space, and then bonding the beads, preferably by heat bonding, into a stable structure.
  • porosity is produced in the matrix to including a foaming agent in the matrix material.
  • porous injectable graft materials are optionally made by adding a degradable gas-producing compound.
  • a degradable gas-producing compound As gas bubbles are produced from the gas-producing compound, pores are formed in the bone-like materials. The size of the pores are preferably controlled by adjusting the amount of gas-producing compound and the viscosity of the mineral matrix in the fluid used to mix the materials.
  • sodium bicarbonate and/or calcium bicarbonate is added to the flowable matrix material and a precise amount of acid (e.g. citric acid, formic, acetic, phosphoric acids, hydrochloric acid) is added to the mixing fluid.
  • the acidity of the mixing fluid causes carbon dioxide to be released from the sodium bicarbonate, wherein the carbon dioxide ultimately forms pores in the matrix material.
  • hydrogen peroxide is combined with peroxidase in the graft material. The peroxidase releases oxygen from the hydrogen peroxide, which has the added advantage of sterilizing the wound site.
  • in-situ porosity can be produced in the matrix material including a porogen with the matrix material, and then in-situ leaching out of the porogen.
  • a porogen is a water-soluble materials.
  • Biodegradable materials can be fabricated into three dimensional anatomical shapes having load bearing properties similar to or exceeding that of natural bone.
  • a matrix component of the osteobiologic component has the capability of being rendered porous and can serve to foster bony fusion.
  • the osteobiologic composition can be implanted without first being rendered to its porous state.
  • Porosity can be achieved after implantation by a faster rate of biodegradation of a pore-forming component of the osteobiologic component relative to a slower rate of degradation of the matrix component of the osteobiologic component.
  • the porous osteobiologic component has sufficient compressive strength and modulus to serve as a bone replacement prosthesis during that period wherein the body regenerates new natural bone within and to the shape of the osteobiologic component.
  • the osteobiologic component is replaced by natural bone as the osteobiologic component biodegrades and by such process is displaced or eliminated from the body by natural processes.
  • the osteobiologic composition comprises at least two components, a continuous matrix component and an included pore-forming component.
  • the matrix component comprises a biodegradable material having a rate of degradation, which at least matches the rate at which the body regenerates natural bone tissue.
  • the pore-forming component is a material, which differs from the matrix material such that it may be differentiated from the matrix component and ultimately be removed therefrom by differential dissolution or biodegradation to provide porosity to the prosthetic template either prior to or after implantation.
  • the molecular weight, molecular weight distribution and degree of crystallinity of the pore-forming polymer is also of significant concern.
  • the pore-forming polymer should biodegrade and/or bioresorb at a rate that is at least four times greater than that of the matrix polymer.
  • the pore-forming polymer should have a polydispersity index of at least 3 to provide for a controlled degradation over a period of time that avoids intolerable localized pH concentrations due to its degradation by-products.
  • the osteobiologic compositions of these embodiments can contain a relatively high ultimate porosity capacity. That is, the osteobiologic composition is fabricated in a manner, which results in an osteobiologic component capable of being rendered highly porous prior to implantation.
  • the matrix may be formed around included particles or fibers which particles or fibers are subsequently removed from the matrix by solvent dissolution or other methods of degradation, leaving a highly porous matrix scaffold structure.
  • the particles or fibers embedded within the formed matrix may be retained in the osteobiologic composition for dissolution or degradation in situ after implantation.
  • portions of the pore-creating material may be removed prior to implantation of the osteobiologic composition providing a range of actual to ultimate porosities of the implantable osteobiologic components.
  • the ultimate porosity capacity may be defined as the percent porosity of the matrix after at least 90% of the pore forming material has been removed from the template, either in vitro or in vivo. In the present invention, it is preferred that the ultimate porosity capacity of the biodegradable/bioresorbable osteobiologic component be in the range of between about 20% and about 50% volume of the osteobiologic component.
  • the biodegradable osteobiologic composition of the present invention which has the porogen features described above, including high mechanical strength necessary for replacement of load bearing bones, high ultimate porosity capacity to permit bony fission therethrough, and a rate of degradation approximately matching the rate of new tissue growth may, for example, be formed by the methods described below.
  • these osteobiologic compositions of the present invention are formed by distributing within a polymeric matrix a pore-creating substance (or “porogen”). Regardless of the specific methods used to form the osteobiologic composition, the product will include a three-dimensional, anatomically-shaped osteobiologic composition having a high ultimate porosity capacity due to the presence of a pore creating substance dispersed within the matrix.
  • the pore creating substance may be formed for example of salts, polysaccharides, protein, polymers other than the matrix polymers, or other non-toxic materials such as gelatin which are, for example, soluble in a solvent which does not dissolve the matrix polymer; made fluid at a higher glass transition temperature (Tg) or melting temperature (Tm) than the matrix polymer; or otherwise differentiated from the matrix polymer so as to retain an independent structure from the polymeric matrix.
  • Tg glass transition temperature
  • Tm melting temperature
  • the temperature required to fluidize polymers is that which permits non-hindered flow of polymer chains.
  • this “flow temperature” is the glass transition temperature (Tg).
  • this “flow temperature” is the melting temperature (Tm).
  • flow temperature is meant to be that temperature which permits non-hindered flow of polymer chains and includes, as appropriate, Tg for amorphous polymers and Tm for at least semi-crystalline polymers.
  • the pore creating substance may be in the form of particles such as salt, which after forming a matrix in which the particles have been included, the particles are leached out or otherwise removed from the matrix leaving a polymeric matrix with high porosity.
  • the pore creating substance may be in the form of fibers such as polymeric fibers or webs dispersed within a formed polymeric matrix. The dispersed fibers and the surrounding matrix possess differential rates of degradation, with the fibers being degraded at a faster rate than the matrix, thereby being removed from the osteobiologic composition and creating a highly porous polymeric, osteobiologic composition.
  • the porogen-containing osteobiologic composition may be formed by dispersing the pore-creating substance in a body of powdered polymer.
  • the pore-creating substance is a first polymer in fiber or web form dispersed in a body of powdered second polymer.
  • the second polymer has a lower flow temperature (Tf) such that when the dispersion is heated above the flow temperature of the powder, the powder is fluid, but the dispersed fibers are not.
  • the fluid polymer is next solidified, e.g., by permitting the dispersion to return to ambient temperature, resulting in a polymeric matrix having entrapped therein the pore-forming substance.
  • a first polymer is used to form the matrix and a second polymer is used to form the pore-creating substance dispersed within the first polymer.
  • Both first and second polymers are biodegradable but the second degrades at a faster rate than the first polymer, e.g., approximately two to eight times faster, and preferably about four times faster creating the desired porous body for ingrowth and proliferation of cells.
  • poly(glycolic acid) (PGA) fiber meshes may be dispersed within poly(L-lactic acid) (PLLA). Upon curing of the PLLA matrix, the PGA fiber mesh is embedded within the PLLA matrix. The PGA fibers biodegrade at a more rapid rate than PLLA, thus creating a template having a high ultimate porosity capacity.
  • the pore creating substance may be formed of a low molecular weight polymer while the matrix is formed of a high molecular weight polymer. Because the low molecular weight polymers degrade at a faster rate than the high molecular weight polymers an implant having a desired rate of degradation of each of the pore creating substance and the matrix can be formed.
  • the matrix has a sufficient number of pores or passageways so that the total accessible surface area of the substrate is at least five times greater than a solid object having the same external dimensions.
  • the preferred total surface area can be achieved by using a substrate, which comprises a mass of powder, a mass of granules, a mass of fibers, or a highly porous block of substrate material.
  • the average pore size in the matrix is greater that 20 ⁇ m, more preferably greater than 50 ⁇ m, more preferably greater than 100 ⁇ m. In some embodiments, the pore size is between about 100 ⁇ m and 250 ⁇ m.
  • the osteobiologic compositions of the present invention have a high ultimate porosity capacity, resulting in a highly porous matrix containing a uniformly distributed and interconnected pore structure.
  • Pore volume of the porous osetobiologic composition is approximately 20% to 90%, and the average pore diameter is approximately 50 to 250 ⁇ m.
  • the pore volume and diameter also directly relate to the rate of tissue ingrowth and matrix degradation.
  • the porous matrix of the present invention accommodates large number of cells adhering to the matrix, permits cells to be easily distributed throughout the template, and allows an organized network of tissue constituents to be formed.
  • the matrix preferably promotes cell adhesion and permits the attached cells to retain differentiated cell function.
  • the leachate produces an open porosity having an average pore size of between 20 ⁇ m and 500 ⁇ m, preferably 50-250 ⁇ m. This range is preferred for bone growth.
  • the matrices of the osteobioloigic component are fabricated of polymers and by methods which result in implants which are capable of being rendered porous for tissue ingrowth while retaining sufficient mechanical strength to be suitable for supporting a disc space.
  • the osteobiologic compositions of the present invention possess a compressive strength of approximately 5 MPa to 50 MPa and a compressive modulus of approximately 50 MPa to 500 MPa as tested by an Instron Materials Testing Machine according to American Society for Testing and Materials (ASTM) Standard F451-86.
  • the values of 5 MPa compressive strength and 50 MPa compressive modulus correspond to the mid-range values for human trabecular bone.
  • the biodegradable, bioresorbable matrices of the present invention preferably are formed of polymeric materials, the matrix polymer having a rate of degradation which is matched to the rate of tissue in-growth.
  • the matrix polymeric substance preferably ranges in weight average molecular weight from approximately 50,000 to 200,000. Crystallinity of the matrix polymer of implant is approximately 0 to 25%.
  • the molecular weight and molecular weight distribution of the matrix polymer is related to the rate at which the matrix biodegrades. In a matrix of broad molecular weight distribution, e.g., having a polydispersity index (Mw/Mn) greater than 2 fractions of the material exist in short to long polymeric chains.
  • the polydispersity index of the matrix is preferably in the range of 3-6.
  • mesenchymnal stem cells are then delivered into the porous matrix.
  • the mesenchymnal stem cells are delivered into the porosity of the scaffold by simply directing an aqueous solution containing mesenchymnal stem cells into the scaffold.
  • an additional cannula can be placed near the porous matrix to serve as an exit cannula for the fluid.
  • a hydrophilic matrix material such as polylactic acid may be used.
  • a lining material such as hydroxyapatite (HA) may be used to line the inner surface of the scaffold with a material to which mesenchymnal stem cells more tenaciously adhere.
  • HA hydroxyapatite
  • cell adhesion molecules may be bound to the inner surface of the matrix in order to enhance the adhesion of the mesenchymnal stem cells to the scaffold.
  • cell adhesion molecules refers collectively to laminins, fibronectin, vitronectin, vascular cell adhesion molecules (V-CAM), intercellular adhesion molecules (I-CAM), tenascin, thrombospondin, osteonectin, osteopontin, bone sialoprotein, and collagens.
  • the mesenchymnal stem cells are delivered into the in-situ porosity under pressure, such as by injection.
  • the envelope is the strut component having a 360 degree span.
  • the envelope can be an inflatable device component of the osteobiologic composition.
  • the mesenchymnal stem cells are delivered into the in-situ porosity under a higher pressure that is sufficient to fill 90% of the porosity.
  • the pressure is high enough to completely fill the porosity.
  • the osteobiologic component of the present invention further comprises a gelled aqueous phase, wherein viable mesenchymnal stem cells are located in the aqueous phase.
  • mesenchymnal stem cells and many growth factors are very heat sensitive, it is desirable to deliver mesenchymnal stem cells and growth factors at or near body temperature.
  • many of the bioabsorbable polymers are flowable at temperatures well in excess of body temperature.
  • many cross-linked polymers experience an exotherm of over 100° C. It is not known whether mesenchymnal stem cells and growth factors could remain viable after prolonged exposure to these temperatures.
  • calcium phosphate can be made flowable at body temperature, it is desirable to select an osteobiologic composition having a matrix comprising calcium phosphate when also choosing to deliver the mesenchymnal stem cells or growth factors to the disc space during the delivery of the matrix component of the osteobiologic composition.
  • an osteobiologic composition that is flowable at body temperature, the composition comprising a matrix comprising calcium phosphate and an osteogenic component.
  • Hydrogels are useful in this respect because they can adequately protect bone growth cells contained therein.
  • a “hydrogel” is a substance formed when an organic polymer (natural or synthetic) is set or solidified to create a three-dimensional open-lattice structure that entraps molecules of water or other solution to form a gel.
  • the solidification can occur, e.g., by aggregation, coagulation, hydrophobic interactions, or cross-linking.
  • the hydrogels employed in this invention rapidly solidify to keep the cells at the application site, thereby eliminating problems of phagocytosis or cellular death and enhancing new cell growth at the application site.
  • the hydrogels are also biocompatible, e.g., not toxic, to cells suspended in the hydrogel.
  • a “hydrogel-cell composition” is a suspension of a hydrogel containing desired tissue precursor cells. These cells can be isolated directly from a tissue source or can be obtained from a cell culture.
  • a “tissue” is a collection or aggregation of particular cells embedded within its natural matrix, wherein the natural matrix is produced by the particular living cells.
  • the hydrogel-cell composition forms a uniform distribution of cells with a well-defined and precisely controllable density. Moreover, the hydrogel can support very large densities of cells, e.g., 50 million cells/ml. These factors improve the quality and strength of the new tissue. In addition, the hydrogel allows diffusion of nutrients and waste products to, and away from, the cells, which promotes tissue growth.
  • Hydrogels suitable for use in the osteobiologic composition of the present invention are water-containing gels, i.e., polymers characterized by hydrophilicity and insolubility in water. See, for instance, “Hydrogels”, pages 458-459 in Concise Encyclopedia of Polymer Science and Engineering, Eds. Mark et al., Wiley and Sons, 1990, the disclosure of which is incorporated herein by reference. Although their use is optional in the present invention, the inclusion of hydrogels is highly preferred since they tend to contribute a number of desirable qualities. By virtue of their hydrophilic, water-containing nature, hydrogels generally can:
  • Suitable hydrogels generally exhibit an optimal combination of such properties as compatibility with the matrix polymer of choice, and biocompatability.
  • the hydrogel phase is preferably between about 50 and about 90 volume percent of the total volume, more preferably between about 70 and about 85 volume percent.
  • the osteobiologic component is a stand-alone component (i.e., there is essentially no strut)
  • the osetobiologic composition will preferably contain a hydrogel phase at a concentration of between about 15 and 50 volume percent, and preferably between about 20 and about 30 volume percent of the osteobiologic composition.
  • the lower levels of the hydrogel phase provide additional opportunity to use a strong matrix in the osteobiologic component.
  • Polymer-hydrogel composites demonstrate an optimal combination of physical/chemical properties, particularly in terms of their conformational stability, resorption characteristics, biocompatability, and physical performance, e.g., physical properties such as density, thickness, and surface roughness, and mechanical properties such as load-bearing strength, tensile strength, static shear strength, fatigue of the anchor points, impact absorption, wear characteristics, and surface abrasion.
  • an unsupported hydrogel is not sufficiently stiff or strong to survive the high spinal loads experienced during the fusion process. Accordingly, in many embodiments of the present invention, the hydrogel is supported not only by the strut component of the present invention, but also by the matrix component of the osteobiologic component. In these cases, the hydrogel is either delivered into the disc space along with the matrix component (as is preferred when the matrix component of the osteobiologic component comprises CaPO 4 ), or is delivered after in-situ porosity has been produced in the matrix component of the osteobiologic component (as with flowable polymers).
  • the strut component of the present invention may span a sufficiently large portion of the disc space and have sufficient stiffness to adequately support and contain the hydrogel phase within the disc space without the need of a supplemental matrix in the osetobiologic component.
  • the strut component preferably describes an arc of at least 200 degrees about the disc space, more preferably at least 270 degrees, more preferably at least 350 degrees, and most preferably is about 360 degrees.
  • Such struts are exemplified in FIGS. 2 ( a ) through ( e ), FIGS. 4 ( a ) and ( b ) and FIGS. 5 ( a ) and ( b ).
  • an intervertebral body fusion device comprising:
  • an osteobiologic component consisting essentially of:
  • an aqueous phase comprising an osteogenic component.
  • the hydrogel can include any of the following: polysaccharides, proteins, polyphosphazenes, poly(oxyethylene)-poly(oxypropylene) block polymers, poly(oxyethylene)-poly(oxypropylene) block polymers of ethylene diamine, poly(acrylic acids), poly(methacrylic acids), copolymers of acrylic acid and methacrylic acid, poly(vinyl acetate), and sulfonated polymers.
  • these polymers are at least partially soluble in aqueous solutions, e.g., water, or aqueous alcohol solutions that have charged side groups, or a monovalent ionic salt thereof.
  • aqueous solutions e.g., water, or aqueous alcohol solutions that have charged side groups, or a monovalent ionic salt thereof.
  • polymers with acidic side groups that can be reacted with cations e.g., poly(phosphazenes), poly(acrylic acids), and poly(methacrylic acids).
  • acidic groups include carboxylic acid groups, sulfonic acid groups, and halogenated (preferably fluorinated) alcohol groups.
  • polymers with basic side groups that can react with anions are poly(vinyl amines), poly(vinyl pyridine), and poly(vinyl imidazole).
  • Water soluble polymers with charged side groups are cross-linked by reacting the polymer with an aqueous solution containing multivalent ions of the opposite charge, either multivalent cations if the polymer has acidic side groups, or multivalent anions if the polymer has basic side groups.
  • Cations for cross-linking the polymers with acidic side groups to form a hydrogel include divalent and trivalent cations such as copper, calcium, aluminum, magnesium, and strontium. Aqueous solutions of the salts of these cations are added to the polymers to form soft, highly swollen hydrogels.
  • Anions for cross-linking the polymers to form a hydrogel include divalent and trivalent anions such as low molecular weight dicarboxylate ions, terepthalate ions, sulfate ions, and carbonate ions. Aqueous solutions of the salts of these anions are added to the polymers to form soft, highly swollen hydrogels, as described with respect to cations.
  • a useful polymer size in the hydrogel is in the range of between 10,000 D and 18,500 D. Smaller polymers result in gels of higher density with smaller pores.
  • Ionic polysaccharides such as alginates or chitosan
  • the hydrogel is produced by cross-linking the anionic salt of alginic acid, a carbohydrate polymer isolated from seaweed, with ions, such as calcium cations.
  • the strength of the hydrogel increases with either increasing concentrations of calcium ions or alginate.
  • U.S. Pat. No. 4,352,883 describes the ionic cross-linking of alginate with divalent cations, in water, at room temperature, to form a hydrogel matrix.
  • Tissue precursor cells are mixed with an alginate solution, the solution is delivered to an already implanted support structure and then solidifies in a short time due to the presence in vivo of physiological concentrations of calcium ions.
  • the solution is delivered to the support structure prior to implantation and solidified in an external solution containing calcium ions.
  • the hydrogel comprises alginate.
  • Alginate can be gelled under mild conditions, allowing cell immobilization with little damage. Binding of Mg 2+ and monovalent ions to alginate does not induce gelation of alginate in aqueous solution. However, exposure of alginate to soluble calcium leads to a preferential binding of calcium and subsequent gelling. These gentle gelling conditions are in contrast to the large temperature or solvent changes typically required to induce similar phase changes in most materials.
  • Alginates have been utilized as immobilization matrices for cell, as an injectable matrix for engineering cartilaginous tissue to treat vesicoureteral reflux in various animal models, and as injectable microcapsules containing islet cells to treat animal models of diabetes.
  • alginate membrane can be modified by incorporating other polymeric elements (e.g., lysine, poly(ethylene glycol), poly(vinyl alcohol) or chitosan). These modified systems have been used to control the release of proteins from alginate beads.
  • Haemostatic swabs made of calcium alginate have also been clinically utilized to reduce blood loss during surgical procedures.
  • the calcium ions in alginate may assist the blood clotting process by activating platelets and clotting factor VII.
  • Collagen-polysaccharide-hydroxyapatite compositions suitable for a matrix of the present invention have been disclosed by Liu in U.S. Pat. No. 5,972,385, the entire teachings of which are incorporated herein by reference.
  • a polysaccharide is reacted with an oxidizing agent to open sugar rings on the polysaccharide to form aldehyde groups.
  • the aldehyde groups are reacted to form covalent linkages to collagen.
  • polysaccharides which can be used include hyaluronic acid, chondroitin sulfate, dermatan sulfate, keratan sulfate, heparan, heparan sulfate, dextran, dextran sulfate, alginate, and other long chain polysaccharides.
  • the polysaccharide is hyaluronic acid.
  • a crosslinked collagen-polysaccharide matrix of the present invention may be used alone to conduct the growth of tissue; in combination with a growth factor to induce the growth of tissue; in combination with fibrin to anchor the matrix into sites of tissue defect, or in combination with both growth factor and fibrin.
  • the method of making a collagen-polysaccharide matrix of the present invention comprises the steps of oxidizing an exogenous polysaccharide to form a modified exogenous polysaccharide having aldehyde groups, and reacting the modified exogenous polysaccharide with collagen under conditions such that the aldehyde groups covalently react with collagen to form a crosslinked matrix.
  • the method may further comprise the step of adding a growth factor to the matrix.
  • a growth factor can be added before or after the step of reacting the modified polysaccharide with the collagen.
  • the fibrin used in a crosslinked collagen-polysaccharide matrix of the present invention is prepared by contacting a preformed matrix with a source of fibrinogen and thrombin or by combining the fibrinogen and thrombin with the modified exogenous polysaccharide and collagen at the time of reaction.
  • fibrinogen and thrombin in a collagen polysaccharide matrix may be added to another preformed collagen polysaccharide matrix. Therefore, the present invention also comprises a method for preparing a crosslinked collagen-polysaccharide matrix comprising fibrin.
  • the hydrogel comprises a microbial polysaccharide.
  • Microbial polysaccharides are ubiquitous in nature and very abundant biopolymers. They are of interest because of their unusual and useful functional properties. Some of these properties are summarized as follows: (i) film-forming and gel-forming capabilities, (ii) stability over broad temperature ranges, (iii) biocompatibility (natural products avoid the release/leaching of toxic metals, residual chemicals, catalyst, or additives), (iv) unusual rheological properties, (v) biodegradability, (vi) water solubility in the native state or reduced solubility if chemically modified, and (vii) thermal processability for some of these polymers. It is worthy to note that gellan, one of the microbial polysaccharides, has been investigated as immobilization materials for enzymes and cells.
  • the hydrogel is a synthetic hydrogel.
  • One synthetic hydrogel is polyphosphazene.
  • Polyphosphazenes contain inorganic backbones comprised of alternating single and double bonds between nitrogen and phosphorus atoms, in contrast to the carbon-carbon backbone in most other polymers.
  • the uniqueness of polyphosphazenes stems from the combination of this inorganic backbone with versatile side chain functionalities that can be tailored for different applications.
  • the degradation of polyphosphazenes results in the release of phosphate and ammonium ions along with the side groups.
  • Linear, uncross-linked polymers such as polyphosphazenes can be prepared by thermal ring opening polymerization of (NPCl 2 ) 3 and the chloro group replaced by amines, alkoxides or organometallic reagents to form hydrolytically stable, high molecular weight poly(organophosphazenes).
  • the polyphosphazenes can be hydrophobic, hydrophilic or amphiphilic.
  • the polymers can be fabricated into films, membranes and hydrogels for biomedical applications by cross-linking or grafting.
  • Bioerodible polymers for drug delivery devices have been prepared by incorporating hydrolytic side chains of imidazole for skeletal tissue regeneration.
  • Polyphosphazenes are polymers with backbones consisting of nitrogen and phosphorous atoms separated by alternating single and double bonds. Each phosphorous atom is covalently bonded to two side chains. Polyphosphazenes that can be used have a majority of side chains that are acidic and capable of forming salt bridges with di- or trivalent cations. Examples of acidic side chains are carboxylic acid groups and sulfonic acid groups.
  • Bioerodible polyphosphazenes have at least two differing types of side chains, acidic side groups capable of forming salt bridges with multivalent cations, and side groups that hydrolyze under in vivo conditions, e.g., imidazole groups, amino acid esters, glycerol, and glucosyl.
  • Bioerodible or biodegradable polymers i.e., polymers that dissolve or degrade within a period that is acceptable in the desired application (usually in vivo therapy), will degrade in less than about five years and most preferably in less than about one year, once exposed to a physiological solution of pH 6-8 having a temperature of between about 25° C. and 38° C. Hydrolysis of the side chain results in erosion of the polymer. Examples of hydrolyzing side chains are unsubstituted and substituted imidizoles and amino acid esters in which the side chain is bonded to the phosphorous atom through an amino linkage.
  • PVA poly (vinyl)alcohol
  • PVA poly (vinyl)alcohol
  • Polyvinyl acetate is usually prepared by radical polymerization of vinyl acetate (bulk, solution or emulsion polymerizations).
  • PVA is formed by either alcoholysis, hydrolysis or aminolysis processes of poly(vinyl acetate).
  • the hydrophilicity and water solubility of PVA can be readily controlled by the extent of hydrolysis and molecular weight. PVA has been widely used as thickening and wetting agent.
  • PVA gels can be prepared by cross-linking with formaldehyde in the presence of sulfuric acid. These formaldehyde-cross-linked PVA materials have been used as prosthesis for a variety of plastic surgery applications including breast augmentation, diaphragm replacement and bone replacement. However, a variety of complications were found after long term implantation, including calcification of the PVA.
  • PVA was made into an insoluble gel using a physical cross-linking process. These gels were prepared with a repeated freezing-thawing process. This causes structural densification of the hydrogel due to the formation of semicrystalline structures. The use of this gel in drug delivery applications has been reported. However, PVA is not truly biodegradable due to the lack of labile bonds within the polymer bond. Only low molecular weight materials are advisable to be used as implant materials.
  • PEO polyethylene oxide
  • PEO polyethylene oxide
  • PEO can be produced by the anionic or cationic polymerization of ethylene oxide using a variety of initiators.
  • PEO is highly hydrophilic and biocompatible, and has been utilized in a variety of biomedical applications including preparation of biologically relevant conjugates, induction of cell membrane fusion and surface modification of biomaterials.
  • Different polymer architectures have been synthesized and some of their applications in medicine have been recently reviewed.
  • PEO can be made into hydrogels by 7-ray or electron beam irradiation and chemical crosslinking. These hydrogels have been used as matrices for drug delivery and cell adhesion studies.
  • Pluronic polyols or polyoxamers are block copolymers of PEO and poly(propylene oxide) and are usually synthesized by anionic polymerization in the form of an ABA triblock using a difunctional initiator.
  • Pluronics F 127 which contains 70% ethylene oxide and 30% propylene oxide by weight with an average molecular weight of 11,500, is the most commonly used gel-forming polymer matrix to deliver proteins.
  • This polymer exhibits a reversible thermal gelation in aqueous solutions at a concentration of 20% or more.
  • the polymer solution is a liquid at room temperature but gels rapidly in the body. Although the polymer is not degraded by the body, the gels dissolve slowly and the polymer is eventually cleared.
  • This polymer has been utilized in protein delivery and skin burn treatments.
  • PGA is not water soluble, bioerodible hydrogels based on photopolymerized PGA-PEO copolymers have been synthesized and their biological activities investigated. Macromonomers having a poly(ethylene glycol) central block, extended with oligomers of .alpha.-hydroxy acids (e.g., oligo(dl-lactic acid) or oligo(glycolic acid)) and terminated with acrylate groups were synthesized. These hydrogels were designed to form direct contacts with tissues or proteins following photopolymerization, and act as a barrier.
  • oligomers of .alpha.-hydroxy acids e.g., oligo(dl-lactic acid) or oligo(glycolic acid)
  • hydrogels that can be used in the methods of the invention are solidified by either visible or ultraviolet light.
  • These hydrogels are made of macromers including a water soluble region, a biodegradable region, and at least two polymerizable regions as described in U.S. Pat. No. 5,410,016, the entire teachings of which are incorporated herein by reference.
  • the hydrogel can begin with a biodegradable, polymerizable macromer including a core, an extension on each end of the core, and an end cap on each extension.
  • the core is a hydrophilic polymer
  • the extensions are biodegradable polymers
  • the end caps are oligomers capable of cross-linking the macromers upon exposure to visible or ultraviolet light, e.g., long wavelength ultraviolet light.
  • Examples of such light solidified hydrogels include polyethylene oxide block copolymers, polyethylene glycol polylactic acid copolymers with acrylate end groups, and 10 K polyethylene glycol-glycolide copolymer capped by an acrylate at both ends.
  • the copolymers comprising these hydrogels can be manipulated by standard techniques to modify their physical properties such as rate of degradation, differences in crystallinity, and degree of rigidity.
  • the osteobiologic composition is delivered into the disc space at a temperature of between about 37° C. and about 60° C., preferably between about 40° C. and about 50° C., more preferably between about 40° C. and about 45° C.
  • a semipermeable membrane is formed around the hydrogel to protect the cells inside.
  • Lin the techniques disclosed in U.S. Pat. No. 4,352,883 by Lin, the entire teachings of which are incorporated herein by reference (hereinafter “Lin”), are used.
  • the instant invention provides a method of encapsulating bone growth cells or growth factors in a semipermeable membrane.
  • the basic approach involves suspending the bone growth cells or growth factors to be encapsulated in a physiologically compatible medium containing a water-soluble substance that can be made insoluble in water, that is, gelled, to provide a temporary protective environment for the tissue.
  • the medium is next formed into droplets containing the bone growth cells or growth factors and gelled, for example, by changing conditions of temperature, pH, or ionic environment.
  • the “temporary capsules” thereby produced are then subjected to a treatment, which can be a known treatment, that results in the production of membranes of a controlled permeability (including impermeability) about the shape-retaining temporary capsules.
  • the temporary capsules can be fabricated from any nontoxic, water soluble substance that can be gelled to form a shape retaining mass by a change of conditions in the medium in which it is placed, and also may comprise plural groups that are readily ionized to form anionic or cationic groups. The presence of such groups in the polymer enables surface layers of the capsule to be cross-linked to produce a “permanent” membrane when exposed to polymers containing multiple functionalities of the opposite charge.
  • the presently preferred material for forming the temporary capsules is polysaccharide gums, either natural or synthetic, of the type which can be (a) gelled to form a shape retaining mass by being exposed to a change in conditions such as a pH change or by being exposed to multivalent cations such as Ca ++ ; and (b) permanently “crosslinked” or hardened by polymers containing reactive groups such as amine or imine groups which can react with acidic polysaccharide constituents.
  • the presently preferred gum is alkali metal alginate.
  • Other water soluble gums which may be used include guar gum, gum arabic, carrageenan, pectin, tragacanth gum, xanthan gum or acidic fractions thereof.
  • gelatin or agar may be used in place of the gums.
  • the preferred method of formation of the droplets is to force the gum-nutrient-tissue suspension through a vibrating capillary tube placed within the center of the vortex created by rapidly stirring a solution of a multivalent cation. Droplets ejected from the tip of the capillary immediately contact the solution and gel as spheroidal shaped bodies.
  • the preferred method of forming a permanent semipermeable membrane about the temporary capsules is to “crosslink” surface layers of a gelled gum of the type having free acid groups with polymers containing acid reactive groups such as amine or imine groups. This is typically done in a dilute solution of the selected polymer. Generally, the lower the molecular weight of the polymer, the greater the penetration into the surface of the temporary capsule, and the greater the penetration, the less permeable the resulting membrane. Permanent crosslinks are produced as a consequence of salt formation between the acid reactive groups of the crosslinking polymer and the acid groups of the polysaccharide gum. Within limits, semipermeability can be controlled by setting the molecular weight of the crosslinking polymer, its concentration, and the duration of reaction.
  • Crosslinking polymers which have been used with success include polyethylenimine and polylysine. Molecular weight can vary, depending on the degree of permeability required, between about 3,000 and about 100,000 or more. Good results have been obtained using polymers having an average molecular weight on the order of about 35,000.
  • the capsules can be engineered to have a selected in vivo useful life by astute selection of the cross-linking polymer.
  • Proteins or polypeptide crosslinkers e.g., polylysine
  • Cross-linkers not readily degradable in mammalian bodies, e.g., polyethyleneimine, result in longer lasting membranes.
  • the temporary capsules it is possible to improve mass transfer within the capsule after formation of the permanent membrane by re-establishing the conditions under which the material is liquid, e.g., removing the multivalent cation. This can be done by ion exchange, e.g., immersion in phosphate buffered saline or citrate buffer. In some situations, such as where it is desired to preserve the encapsulated tissue, or where the temporary gelled capsule is permeable, it may be preferable to leave the encapsulated gum in the crosslinked, gelled state.
  • An alternative method of membrane formation involves an interfacial polycondensation of polyaddition.
  • the instant invention provides a tissue implantation method which does not require surgery and which overcomes many of the problems of immune rejection.
  • the capsules are injected into a suitable site in a mammalian body, and function normally until the tissue expires, or until natural body processes succeed in isolating the capsules so that substances required for viability of the tissue are no longer available.
  • the mammalian body may accordingly be provided with the specialized function of the tissue as long as desired.
  • mammalian mesenchymal stems cells are encapsulated in polylysine and polyethyleneimine cross-linked alginate membranes. These may be injected into the polymer matrix of the osteobiologic component.
  • Other objects of the invention are to provide a method of implanting living tissue in mammalian bodies and to provide a non-surgical tissue implantation technique. Still another object is to provide a method of encapsulating living tissue which allows the production of capsules having a high surface area to volume ratio and membranes with a preselected in vivo residence time.
  • each of IPNs and S-IPNs are extremely desirable because cells can be suspended in the polymer solutions which can be cross-linked by a non-toxic active species, such as by photoinitiation.
  • a non-toxic active species such as by photoinitiation.
  • both the active species and the initiator are present in an amount that is non-toxic to cells.
  • the active species is present in an amount that is non-toxic to cells and the initiation occurs via photoinitiation.
  • Cells can be obtained directed from a donor, from cell culture of cells from a donor, or from established cell culture lines. In the preferred embodiments, cells are obtained directly from a donor, washed and implanted directly in combination with the polymeric material. The cells are cultured using techniques known to those skilled in the art of tissue culture.
  • Cell attachment and viability can be assessed using scanning electron microscopy, histology, and quantitative assessment with radioisotopes.
  • the function of the implanted cells can be determined using a combination of the above-techniques and functional assays. For example, in the case of hepatocytes, in vivo liver function studies can be performed by placing a cannula into the recipient's common bile duct. Bile can then be collected in increments.
  • Bile pigments can be analyzed by high pressure liquid chromatography looking for underivatized tetrapyrroles or by thin layer chromatography after being converted to azodipyrroles by reaction with diazotized azodipyrroles ethylanthranilate either with or without treatment with P-glucuronidase.
  • Diconjugated and monoconjugated bilirubin can also be determined by thin layer chromatography after alkalinemethanolysis of conjugated bile pigments. In general, as the number of functioning transplanted hepatocytes increases, the levels of conjugated bilirubin will increase. Simple liver function tests can also be done on blood samples, such as albumin production.
  • Analogous organ function studies can be conducted using techniques known to those skilled in the art, as required to determine the extent of cell function after implantation.
  • islet cells of the pancreas may be delivered in a similar fashion to that specifically used to implant hepatocytes, to achieve glucose regulation by appropriate secretion of insulin to cure diabetes.
  • Other endocrine tissues can also be implanted.
  • Studies using labeled glucose as well as studies using protein assays can be performed to quantitate cell mass on the polymer scaffolds. These studies of cell mass can then be correlated with cell functional studies to determine what the appropriate cell mass is.
  • function is defined as providing appropriate structural support for the surrounding attached tissues.
  • This technique can be used to provide multiple cell types, including genetically altered cells, within a three-dimensional scaffolding for the efficient transfer of large number of cells and the promotion of transplant engraftment for the purpose of creating a new tissue or tissue equivalent. It can also be used for immunoprotection of cell transplants while a new tissue or tissue equivalent is growing by excluding the host immune system.
  • Examples of cells which can be implanted as described herein include chondrocytes and other cells that form cartilage, osteoblasts and other cells that form bone, muscle cells, fibroblasts, and organ cells.
  • organ cells includes hepatocytes, islet cells, cells of intestinal origin, cells derived from the kidney, and other cells acting primarily to synthesize and secret, or to metabolize materials.
  • the osteobiologic component comprises an osteoconductive phase.
  • the osteoconductive phase comprises a particulate phase comprising a hard tissue, osteoconductive or osteoinductive calcium containing, non-fibrous, powdered compound, wherein the calcium containing compound comprises a material having the formula:
  • M and N are alkali or alkaline earth metals, preferably calcium, magnesium, sodium, zinc and potassium.
  • ZO 4 is an acid radical, where Z is preferably phosphorus, arsenic, vanadium, sulfur or silicon, or is substituted in whole or part with carbonate (CO 3 2- .
  • Y is an anion, preferably halide, hydroxide, or carbonate.
  • the calcium containing compound comprises mono-, di-, octa-, .alpha.-tri-, .beta.-tri-, or tetra-calcium phosphate, hydroxyapatite, fluorapatite, calcium sulfate, calcium fluoride and mixtures thereof.
  • the calcium containing bone regenerating compound can also contain a bioactive glass comprising metal oxides such as calcium oxide, silicon dioxide, sodium oxide, phosphorus pentoxide, and mixtures thereof, and the like.
  • the calcium containing compound used in the composites of the present invention will have a particle size of about 10 microns to about 1000 microns, and most preferably about 100 microns to about 500 microns.
  • the particles are prepared by conventional processes such as pulverizing, milling, and the like.
  • hydroxyapatite particles are preferably the type of dry free-flowing hydroxyapatite particles supplied for use in forming wetted, loose-mass implants, and can be obtained commercially from Orthomatrix Corporation (Dublin, Calif.) or Calcitek (San Diego, Calif.). Particle sizes of between about 250 and 2000 microns are preferred, smaller particles showing increased difficulty in allowing tissue ingrowth and larger particles requiring increased quantities of binder for ease of application.
  • the material comprising the osteobiologic component of the present invention has at least one of the following intrinsic properties: More Intrinsic Property Preferred Value Preferred Value Compression Strength >1 MPa >10 MPa Fracture Strength >1 MPa >10 MPa Compression Modulus 0.1-2 GPa 0.2-0.7 GPa
  • the osteobiologic component of the present invention has the following mechanical performance characteristics: More Mechanical Property Preferred Value Preferred Value Static Compressive Load >2 kN >4 kN
  • One example of such an osteobiologic composition comprises an in situ formed, porous, polyoxaester scaffold that occupies the space created by the strut described in FIGS. 2 ( f ) and 2 ( g ).
  • the polymer has a Tm of no more than about 80° C. This allows the use of water or steam as the heating fluid. In some embodiments, the polymer has a Tm of less than 100° C., and so is less likely to damage surrounding tissue.
  • preferred embodiments in the solidifed form, exhibit mechanical properties approximating those of the cancellous bone.
  • preferred embodiments of the osetobiologic composition exhibit a load bearing strength of between about 50 and about 200 psi (pounds per square inch), and preferably between about 100 and about 150 psi.
  • Such composites also exhibit a shear stress of between about 10 and 100 psi, and preferably between about 30 and 50 psi, as such units are typically determined in the evaluation of natural tissue and joints.
  • growth factors encompasses any cellular product that modulates the growth or differentiation of other cells, particularly connective tissue progenitor cells.
  • the growth factors that may be used in accordance with the present invention include, but are not limited to, FGF-1, FGF-2, FGF-4, PDGFs, EGFs, IGFs, PDGF-bb, bone morphogenetic protein-1, bone morphogenetic protein-2, OP-1, transforming growth factor- ⁇ , osteoid-inducing factor (OIF), angiogenin(s), endothelins, hepatocyte growth factor and keratinocyte growth factor, osteogenin (bone morphogenetic protein-3); bone morphogenetic protein-2; OP-1; bone morphogenetic protein-2A, -2B, and -7; transforming growth factor- ⁇ , HBGF-1 and -2; isoforms of platelet-derived growth factors (PDGF), fibroblast growth factors, epithelial growth factors, isoforms of PDGF-1, fibroblast growth factors,
  • Growth factors which can be used with a matrix of the present invention include, but are not limited to, members of the transforming growth factor- ⁇ superfamily, including transforming growth factor- ⁇ 1,2 and 3, the bone morphogenetic proteins (BMP's), the growth differentiation factors (GDF's), and ADMP-1; members of the fibroblast growth factor family, including acidic and basic fibroblast growth factor (FGF-1 and -2); members of the hedgehog family of proteins, including indian, sonic and desert hedgehog; members of the insulin-like growth factor (IGF) family, including IGF-I and -II; members of the platelet-derived growth factor (PDGF) family, including PDGF-AB, PDGF-BB and PDGF-AA; members of the interleukin (IL) family, including IL-1 thru -6; and members of the colony-stimulating factor (CSF) family, including CSF-1, G-CSF, and GM-CSF.
  • BMP's bone morphogenetic proteins
  • GDF's growth
  • osteogenic components and osteoinductive components in a heated polymer matrix may render nonviable or denature these components.
  • growth factors known to those skilled in the art that are more heat resistant than the majority of growth factors. It is believed that these high temperature growth factors in osteobiologic compositions may be included in osteobiologic compositions that are to be flowed into the disc space at temperatures between body temperature and about 45° C.
  • the present invention is a pharmaceutical composition
  • a pharmaceutically acceptable carrier or diluent and (a) at least one polymer flowable between 38° C. and 45° C. selected from the group consisting of homopolymers of poly( ⁇ -caprolactone), poly(p-dioxanone), or poly(trimethylene carbonate) or copolymers or mixtures thereof, or copolyesters of p-dioxanone or trimethylene carbonate and glycolide or lactide or mixtures thereof, and in particular, copolymers of p-dioxanone/glycolide, p-dioxanone/lactide, trimethylene carbonate/glycolide and trimethylene carbonate/lactide, or copolyesters of epsilon.-caprolactone and glycolide or mixtures thereof, or mixtures of homopolymers of ⁇ -caprolactone and lactide, and (b) at least one growth factor resistant
  • a “pharmaceutical composition” is a formulation comprising the disclosed compounds and a pharmaceutically acceptable diluent or carrier, in a form suitable for administration to a subject.
  • the quantity of active ingredient (e.g. a growth factor) in a unit dose of composition is an effective amount and may be varied according to the particular treatment involved.
  • an “effective amount” of a compound is the quantity which, when administered to a subject in need of treatment, improves the prognosis of the subject, e.g. reduces the severity of one or more of the subject's symptoms associated with a spinal injury. It may be appreciated that it may be necessary to make routine variations to the dosage depending on the age and condition of the patient.
  • the amount of the active ingredient to be administered to a subject will depend on the type of injury and the characteristics of the subject, such as general health, other diseases, age, sex, genotype, body weight and tolerance to drugs. The skilled artisan will be able to determine appropriate dosages depending on these and other factors.
  • the compounds described herein can be used in pharmaceutical preparations in combination with a pharmaceutically acceptable carrier or diluent.
  • suitable pharmaceutically acceptable carriers include inert solid fillers or diluents and sterile aqueous or organic solutions.
  • the compounds will be present in such pharmaceutical compositions in amounts sufficient to provide the desired dosage amount in the range described herein.
  • Techniques for formulation and administration of the compounds of the instant invention can be found in Remington: the Science and Practice of Pharmacy, 19 th edition, Mack Publishing Co., Easton, Pa. (1995).
  • the matrix material becomes flowable in the temperature range of at least 40° C. and 55° C., more preferably in the temperature range of at least 45° C. and 50° C.
  • the growth factor is resistant to denaturing at a temperature of at least 40° C.
  • the growth factor is a dimer.
  • the growth factor is a bone morphogenetic protein dimer.
  • substances such as antibiotics, antibacterial agents, and antifungal agents may also be admixed with the polymer.
  • antimicrobial agents which may be employed include tetracycline, oxytetracycline, chlorotetracycline, neomycin, erithromycin, and its derivative, bacitracin, streptomycin, rifampicin and its derivatives such as N-dimethylrifampicin, kanamycin and chloromycetin.
  • Useful antifungal agents include griseofulvin, mycostatin, miconazole and its derivatives as described in U.S. Pat. No.
  • cetyl trimethyl ammonium bromide as well as benzethonium chloride and methylbenzethonium chloride such as described in U.S. Pat. Nos.
  • the matrix has antibodies that have affinity for connective tissue progenitor stem cells bound to the surface thereof.
  • Suitable antibodies include by way of example, STRO-1, SH-2, SH-3, SH-4, SB-10, SB-20, and antibodies to alkaline phosphatase. Such antibodies are described in Haynesworth et al., Bone (1992), 13:69-80; Bruder, S. et al., Trans Ortho Res Soc (1996), 21:574; Haynesworth, S.
  • Mac Phee discloses that drugs, polyclonal and monoclonal antibodies and other compounds, including, but not limited to, DBM and bone morphogenetic proteins may be added to the matrix, such as a matrix of the present invention. They accelerate wound healing, combat infection, neoplasia, and/or other disease processes, mediate or enhance the activity of the growth factor in the matrix, and/or interfere with matrix components which inhibit the activities of the growth factor in the matrix.
  • antibiotics such as tetracycline and ciprofloxacin
  • antiproliferative/cytotoxic drugs such as 5-fluorouracil (5-FU), taxol and/or taxotere
  • antivirals such as gangcyclovir, zidovudine, amantidine, vidarabine, ribaravin, trifluridine, acyclovir, dideoxyuridine and antibodies to viral components or gene products
  • cytokines such as ⁇ - or ⁇ - or ⁇ -Interferon, ⁇ - or ⁇ -tumor necrosis factor, and interleukins
  • colony stimulating factors erythropoietin
  • antifungals such as diflucan, ketaconizole and nystatin
  • antiparasitic agents such as pentamidine
  • anti-inflammatory agents such as ⁇ -1-anti-trypsin and ⁇ -1-antichymotrypsin
  • steroids anesthetics
  • anesthetics such as pentamidine
  • Other compounds which may be added to the matrix include, but are not limited to: vitamins and other nutritional supplements; hormones; glycoproteins; fibronectin; peptides and proteins; carbohydrates (both simple and/or complex); proteoglycans; antiangiogenins; antigens; oligonucleotides (sense and/or antisense DNA and/or RNA); bone morphogenetic proteins; DBM; antibodies (for example, to infectious agents, tumors, drugs or hormones); and gene therapy reagents. Genetically altered cells and/or other cells may also be included in the matrix of this invention.
  • substances such as pain killers and narcotics may also be admixed with the polymer for delivery and release to the disc space.
  • the additive is embedded within the matrix material of the scaffold. In other embodiments, the additive resides on the inner surface of the open porosity created by the leaching of the leachate. In other embodiments, the additive resides within the hydrogel phase.
  • the osteobiologic composition comprises one or more bone morphogenetic proteins
  • they are preferably located on the inner surface of the open porosity in the case where the scaffold is formed prior to being populated with cells, and are preferably located within the hydrogel phase in the case where a hydrogel is used to deliver cells at the same time the scaffold is delivered. This is done so that the cells will contact the bone morphogenetic proteins as soon as possible following implantation in order to initiate the bone forming process.
  • the bone morphogenetic proteins have a limited time in which they are active in inducing cells to form bone, it is important to expose the cells to the bone morphogenetic proteins as soon as possible to take maximum advantage of their potency.
  • osteoprogenitor cells When osteoprogenitor cells are seeded onto the scaffold following in situ formation of the scaffold, they preferably adhere to the surface of the inner porosity of the scaffold. This is important because osteoprogenitor cells must attach to a substrate in order to begin forming bone. Likewise when osteoprogenitor cells are delivered to the fusion site while encapsulated in a hydrogel, they preferably attach to the inner porosity of the hydrogel.
  • bone morphogenetic protein is present in the scaffold in a concentration of at least 2 times the atologus concentration. More preferably, the bone morphogenetic protein is present in the scaffold in a concentration of at least 100 times the autologous concentration.
  • mesenchymnal stem cells are present in the scaffold in a concentration of at least 2 times the autologous concentration. More preferably the mesenchymnal stem cells are present in the scaffolding in a concentration of 10 times the autologous concentration, and most preferably they are present in a concentration of 100 times the autologous concentration.
  • the osteobiologic composition has a sufficiently high osteobiologic nature and a matrix that is sufficiently resistant to degradation that the bone growth essentially fills the entire porosity of the scaffold of the osteobiologic composition before there is any significant degradation of the matrix.
  • the new bone can begin to significiantly share the compressive load experienced by the device before the device undergoes a significant loss in strength.
  • bony ingrowth penetrates at least 50% of the distance to the center of the implant before the matrix loses 50% of its weight. In more preferred embodiments, bony ingrowth penetrates at least 75% of the distance to the center of the implant before the matrix loses 25% of its weight. In more preferred embodiments, bony ingrowth penetrates at least 90% of the distance to the center of the implant before the matrix loses 10% of its weight.
  • bony ingrowth penetrates at least 50% of the distance to the center of the implant before the matrix loses 50% of its compressive strength. In more preferred embodiments, bony ingrowth penetrates at least 75% of the distance to the center of the implant before the matrix loses 25% of its compressive strength. In more preferred embodiments, bony ingrowth penetrates at least 90% of the distance to the center of the implant before the matrix loses 10% of its compressive strength.
  • the injectable implants of the invention can be used to fuse facets and to fuse the interspinous region.
  • the implants of the present invention use an elastomer to tension the interspinous region to correct lordotic angle.
  • osteobiologic compositions can be advantageously used in vertebroplasty procedures, particularly when delivered into the porosity of a skeleton created in the vertebral body, as disclosed in U.S. patent application by Martin Reynolds entitled “Method of Performing Embolism Free Vertebroplasty and Devise Therefore,” which was filed on Nov. 21, 2002, the entire teachings of which are incorporated herein by reference.
  • the present invention is an intervertebral fusion device for providing bony fusion across a disc space.
  • the device comprises a strut.
  • the strut includes an upper surface for bearing against the upper endplate, a lower surface for bearing against the lower endplate, and an in-situ formed load bearing composition disposed between the upper and lower surfaces.
  • the present invention is an intervertebral fusion device comprising a strut, having a shape memory, and an in-situ formed osteobiologic component.
  • the strut further includes (i) an upper surface for bearing against the upper endplate and (ii) a lower surface for bearing against the lower endplate.
  • the rpesent invention is an intervertebral fusion device comprising a strut and an in-situ formed osteobiologic component.
  • the strut includes an upper surface for bearing against the upper endplate, and a lower surface for bearing against the lower endplate.
  • the in-situ formed osteobiologic component includes a matrix component having an internal surface defining a scaffold having open porosity suitable for bone growth therethrough, and an osteogenic component located within the open porosity.
  • the present invention is an intervertebral fusion device comprising a strut and an in-situ formed osteobiologic component.
  • the strut includes an upper surface for bearing against the upper endplate, and a lower surface for bearing against the lower endplate.
  • the in-situ formed osteobiologic component includes an injectable matrix component, and an osteoinductive component embedded within the matrix.
  • the present invention is an intervertebral fusion device comprising a strut and an in-situ formed osteobiologic component.
  • the strut includes an upper surface for bearing against the upper endplate, and a lower surface for bearing against the lower endplate.
  • the in-situ formed osteobiologic component includes an injectable matrix component, and a porogen embedded within the matrix.
  • the present invention is an intervertebral fusion device comprising a strut and an in-situ formed osteobiologic component.
  • the strut includes an upper surface for bearing against the upper endplate, and a lower surface for bearing against the lower endplate.
  • the in-situ formed osteobiologic component includes an expandable device defining a cavity, and an injectable osteobiologic composition located within the cavity.
  • the present invention is an intervertebral fusion device comprising a strut that includes an expandable device having a cavity, an upper surface for bearing against the upper endplate, a lower surface for bearing against the lower endplate, and an inner wall defining a through hole.
  • the strut further includes an injectable load bearing composition located within the cavity.
  • the fusuion device further includes an osteobiologic component located in the throughhole.
  • the present invention is an intervertebral fusion device comprising a strut and an in-situ formed osteobiologic component.
  • the strut includes an upper surface for bearing against the upper endplate a lower surface for bearing against the lower endplate.
  • the in-situ formed osteobiologic component includes an injectable, matrix component essentially free of monomer.
  • the present invention is an intervertebral fusion device for providing bony fusion across a disc space, comprising a strut.
  • the strut includes an upper surface for bearing against the upper endplate, a lower surface for bearing against the lower endplate, and an in-situ formed load bearing composition disposed between the upper and lower surfaces and made of a material comprising a cross-linked resorbable polymer.
  • the term “toroid” refers to a surface obtained by at least partially rotating a closed curve, which lies in a plane, about an axis parallel to the plane and which does not intersect the curve.
  • An example of an “open cavity defined by an outer surface of a toroid” is a hole.
  • the present invention is an intervertebral spinal fusion device comprising at least one arcuate inflatable balloon that upon expansion between two adjacent vertebrae at least partially restores natural a natural angle between two adjacent vertebrae, said device having a footprint that substantially corresponds to a perimeter of a vertebral endplate.
  • the intervertebral spinal fusion device has an upper area, a lower area, an anterior area and a posterior area.
  • said device can have a footprint that substantially corresponds to a rim of a vertebral endplate and said anterior area height being greater than said posterior area height.
  • at least a portion of the device has a generally toroidal shape thereby defining an open cavity having an axial dimension and a radial dimension.
  • the device comprises at least one exandable balloon that contains a plurality of lumena.
  • the device comprises at least one said balloon including a resorbable, semi-permeable material selected from the group consisting of polyolefin copolymers, polyethylene, polycarbonate, polyethylene terephthalate, ether-ketone polymers, woven fibers, nonwoven fibers, fabrics and metal mesh.
  • a resorbable, semi-permeable material selected from the group consisting of polyolefin copolymers, polyethylene, polycarbonate, polyethylene terephthalate, ether-ketone polymers, woven fibers, nonwoven fibers, fabrics and metal mesh.
  • the balloon defines at least one opening.
  • the upper and lower areas of the device have a plurality of outward projections.
  • the outward projections preferably include polyetherether ketone (PEEK).
  • the upper area of the device can include at least one material selected from the group consisting of polyether block copolymer (PEBAX), ABS (acrylonitrile butadiene styrene), ANS (acrylonitrile styrene), delrin acetal; PVC (polyvinyl chloride), PEN (polyethylene napthalate), PBT (polybutylene terephthalate), polycarbonate, PEI (polyetherimide), PES (polyether sulfone), PET (polyethylene terephthalate), PETG (polyethylene terephthalate glycol), polyamide, aromatic polyamide, polyether, polyester, polymethylmethacrylate, polyurethane copolymer, ethylene vinyl acetate (EVA), ethylene vinyl alcohol, polyethylene, latex rubber, FEP (fluorinated ethylene polymer), .PTFE (polytetrafluoroethylene), PFA (perfluoro-alkoxyalkane), polypropylene
  • the device of the present invention has at least one balloon that contains at least one member of the group consisting of a load-bearing component and an osteobiologic component.
  • the load-bearing and the osteobiologic components can be used alone or in combination. Combination is preferred.
  • the load-bearing and the osteobiological components are resorbable.
  • the the load-bearing component can comprise at least one compound selected from the group consisting of poly(lactic acid), poly(glycolic acid), p-dioxanone fibers, polyarylethyl, polymethylmethacrylate, polyurethane, amino-acid-derived polycarbonate, polycaprolactone, aliphatic polyesters, calcium phosphate, unsaturated linear polyesters, vinyl pyrrolidone and polypropylene fumarate diacrylate, or mixtures thereof.
  • the osteobiologic component can include at least one element selected from the group consisting of mesenchymal stem cells, growth factors, cancellous bone chips hydroxyapatite, tri-calcium phosphate, polylactic acid, polyglycolic acid, polygalactic acid, polycaprolactone, polyethylene oxide, polypropylene oxide, polysulfone, polyethylene, polypropylene, hyaluronic acid, bioglass, gelatin, collagen and chopped polymeric fibers or mixtures thereof.
  • the term “cancellous” refers to a bone having a porous structure.
  • the normal type of adult mammalian bone, whether cancellous or compact, is composed of parallel lamellae in the former and concentric lamellae in the latter; lamellar organization reflects a repeating pattern of collagen fibroarchitecture.
  • Adult bone consisting of mineralised regularly ordered parallel collagen fibres more loosely organised than the lamellar bone of the shaft of adult long bones, such as bone found in the end of long bones, is known as “cancellous bone”.
  • the device can further comprise an osteoinductive component and an osteoconductive component.
  • the osteoinductive component can include at least one compound selected from the group consisting of fibroblast growth factors, such as (FGFs) FGF-1, FGF-2 and FGF-4; platelet-derived growth factors (PDGFs), such as PDGF-AB, PDGF-BB, PDGF-AA; epithelial growth factors EGFs; insulin-like growth factors (IGF), such as IGF-I, IGF-II; osteogenic protein-I (OP-1); transforming growth factors (TGFs), such as transforming growth factor- ⁇ , transforming growth factor- ⁇ 1, transforming growth factor- ⁇ 2, transforming growth factor- ⁇ 3; osteoid-inducing factor (OIF); angiogenin(s); endothelins; hepatocyte growth factor and keratinocyte growth factor; bone morphogenetic proteins (BMPs), such as osteogenin (bone morphogenetic protein-3), bone morphogenetic protein-2; bone morphogenetic protein-2A, bone morphogenetic protein-2B, bone morphogen
  • the osteoconductive component can include at least one compound selected from the group consisting of a material having the formula:
  • M and N are alkali or alkaline earth metals
  • ZO 4 is an acid radical, where Z is phosphorus, arsenic, vanadium, sulfur or silicon;
  • Y is an anion, preferably halide, hydroxide, or carbonate.
  • the osteoconductive component can further include at least one of material selected from the group consisting of mono-calcium phosphate, di-calcium phosphate, octa-calcium phosphate, alpha-tri-calcium phosphate, beta-tri-calcium phosphate, or tetra-calcium phosphate, hydroxyapatite, fluorapatite, calcium sulfate, calcium fluoride, calcium oxide, silicon dioxide, sodium oxide, and phosphorus pentoxide or mixtures thereof.
  • material selected from the group consisting of mono-calcium phosphate, di-calcium phosphate, octa-calcium phosphate, alpha-tri-calcium phosphate, beta-tri-calcium phosphate, or tetra-calcium phosphate, hydroxyapatite, fluorapatite, calcium sulfate, calcium fluoride, calcium oxide, silicon dioxide, sodium oxide, and phosphorus pentoxide or mixtures thereof.
  • the osteobiologic component can further include at least one water-soluble materials selected from the group consisting of gelatin, salts, polysaccharides and proteins.
  • a particularly preferred embodiment of the present invention is an intervertebral spinal fusion device shown in FIGS. 17 ( a ) (collapsed) and ( b ) (expanded).
  • the device 100 comprises (a) a partially rigid anterior frame 110 detachably connected to a first fluid communication means 120 , said frame having an upper inflatable rim 130 and a lower inflatable rim 140 ; and (b) a rigid posterior expandable frame 150 , detachably connected to a second fluid communication means 122 , said frame having a rigid upper rim 160 and a rigid lower rim 170 , connected respectively to the upper inflatable rim 130 and lower inflatable rim 140 of the anterior frame 110 .
  • the device further comprises at least one mesh element 180 connected to the upper and the lower inflatable rims 130 and 140 of the anterior frame 110 .
  • At least one of the upper and the lower inflatable rims 130 and 140 of the anterior frame 110 of the device 100 can have a plurality of outward projections 190 .
  • the posterior frame 150 of the device further includes at least one telescopically expandable supporting element 200 , each said supporting element being connected to the upper and the lower rigid rims 160 and 170 of the posterior frame 150 .
  • Device 100 can be inserted into an intervertebral space in a collapsed state 210 .
  • Device 100 can next be oriented so that the anterior frame 110 of the device is oriented to face an anterior aspect of a vertebra, the posterior frame 150 of the device is oriented to face a posterior aspect of the vertebra and the upper and lower rims 130 , 140 , 160 and 170 of each frame face upper and lower vertebral endplates endplates, respectively.
  • At least one of the load-bearing component and the osteobiologic component is directed into the device by directing at least one component under pressure through at least one of the first and the second fluid communication means 120 and 122 , thereby causing the device to expand and directing the upper inflatable rim 130 and the lower inflatable rim 140 of the anterior frame and a posterior frame 150 of the device against the respective vertebral endplates, thereby at least partially restoring a natural angle between two adjacent vertebrae.
  • the device upon at least partially filling the upper and lower inflatable rims 130 and 140 and the posterior frame 150 between two adjacent vertebrae (not shown), natural angle between said two vertebrae is at least partially restored.
  • the distance D between the upper and the lower inflatable rims is different from the height h of the posterior frame.
  • said rims upon at least partially filling the upper and the lower inflatable rims 130 and 140 , said rims each have a footprint substantially corresponding to a rim of a vertebral endplate.
  • the device upon at least partially filling the upper and the lower inflatable rims 130 and 140 and the posterior frame 150 , the device defines an open cavity 205 having an axial and a radial dimensions.
  • the present invention is a method of making an intervertebral spinal fusion device comprising (a) inserting an inflatable device through a cannula into an intervertebral space; (b) orienting said inflatable device so that upon expansion a natural angle between two adjacent vertebrae will be at least partially restored; and (c) directing at least one member of the group consisting of a load-bearing component and an osteobiologic component into the inflatable device through the fluid communication means.
  • the method of the present invention further includes the step of hardening the load-bearing component.
  • said inflatable device includes an arcuate balloon connected to at least one fluid communication means, wherein said inflatable device upon expansion between two adjacent vertebrae has a footprint that substantially corresponds to a perimeter of a vertebral endplate and at least partially restores a natural angle between two adjacent vertebrae.
  • said inflatable device includes at least one inflatable balloon, said device having an upper area, a lower area, an anterior area and a posterior area, and where upon expansion of the upper and the lower areas against the respective vertebral endplates, said anterior area is unequal to than said posterior area height, and a footprint of the device substantially corresponds to a rim of a vertebral endplate.
  • the at least one balloon can contain a plurality of lumena.
  • the anterior area of the inflatable device is oriented to face an anterior aspect of a vertebra and the posterior area of the device is oriented to face a posterior aspect of the vertebra.
  • At least one of the load-bearing component and the osteobiologic component is directed into the balloon by directing at least one component under pressure through the fluid communication means, thereby causing the balloon to expand and directing the upper area and the lower area of the device against the respective vertebral endplates, thereby at least partially restoring a natural angle between two adjacent vertebrae.
  • At least a portion of the device used to practice the method of the present invention upon expansion, has a generally toroidal shape thereby forming an open cavity defined by an outer surface of the toroidal shape having an axial dimension and a radial dimension.
  • the at least a portion of the device is oriented so that the axial dimension of the open cavity is substantially parallel to a major axis of a spinal column of a patient in which the device has been implanted.
  • At least one of a load-bearing component and an osteobiologic component can be directed into the open cavity defined by the expanded device.
  • the method of the present invention can further include the step of dissolving at least one water-soluble material, thereby forming a porous matrix.
  • the method of the present invention further includes the step of directing into the inflatable device osteoinductive and/or osteoconductive components.
  • the present invention is a method of at least partially restoring a natural angle between two adjacent vertebrae comprising: (a) inserting an inflatable device through a cannula into an intervertebral space; (b) orienting said inflatable device so that upon expansion a natural angle between two adjacent vertebrae will be at least partially restored; and (c) expanding said inflatable device by directing at least one of a load-bearing component and an osteobiologic component, into said inflatable device.
  • the inflatable devices suitable for practicing the method of the present invention are described above.
  • the method of the present invention includes the step of inflating said inflatable device.
  • Inflating includes introducing at least one of a load-bearing component and an osteobiologic component into said device by directing at least one component through the fluid communication means, thereby allowing the lower area and the upper area to engage the respective endplates and the anterior area height of said inflatable device to be greater than the posterior area height, thereby at least partially restoring or creating a natural angle between two adjacent vertebrae.
  • the method further includes the step of hardening at least one of the load-bearing component and an osteobiologic component.
  • the device upon expansion has a generally toroidal shape thereby forming an open cavity defined by an outer surface of the toroidal shape and having an axial dimension and a radial dimension and the step of orienting said inflatable device includes orienting at least a portion of the device so that so that the axial dimension of the open cavity is substantially parallel to a major axis of a spinal column of a patient in which the device has been implanted.
  • the method further includes the step of introducing at least one of the load-bearing component and the osteobiologic component into the cavity and the step of hardening at least one of the load-bearing component and an osteobiologic component.
  • the method can further includes the step of dissolving at least one water-soluble material, thereby forming a porous matrix.
  • the patient is brought to the pre-surgical area and prepped. Anesthesia is then induced and the area of the spine is further prepped. A small incision through the muscles is opened under dissecting microscopic visualization. The incision is made as small as possible and is longitudinal in the plane of the spine. The paravertebral muscles are separated by blunt dissection and held apart with forceps and dividers. The intervertebral disc area is visualized, with initial exposure down to the lamina. The area below the lamina, at the point of the intervertebral foramina, can also be exposed.
  • the disc is examined for extruded material and any extruded material is removed.
  • Magnetic resonance imaging (“MRI”) data can be used to determine the integrity of the annulus fibrosis at this point.
  • An arthroscope is inserted into the disc and used to examine the inside of the annulus.
  • an intraoperative discogram can be performed, in which a dye material is inserted and visualized in order to substantiate the integrity of the annulus fibrosis.
  • Points of weakness, or rents, in the annulus fibrosis are identified and located and suitable means, e.g., a bioabsorbable glue is employed to block these rents. If balloons are used to deliver all of the flowable materials used in the present invention, then the rents need not be patched.
  • Distraction of the intervertebral disc space can then be accomplished, as described above, by inserting a deflated balloon into the disc space and delivering a fluid (preferably, the flowable load bearing component of the present invention) into the balloon cavity.
  • a fluid preferably, the flowable load bearing component of the present invention
  • the endplates of the opposing vertebral body are partially decorticated, typically through the use of a curette, in order to allow blood flow into the disc space.
  • the application cannula is inserted into the joint or disc space and under visualization from the fiberoptic scope the biomaterial is delivered.
  • the flow of the biomaterial is controlled by the operator via a foot pedal connected to the pumping mechanism on the polymer canister.
  • the biomaterial flows from the tip of the application catheter to fill the space provided.
  • the load bearing component has a flowable component
  • the flowable component is preferably solidified within 3 to 5 minutes, and preferably within 1 to 2 minutes.
  • the osteobiologic component of the present invention is introduced to the distracted space, thereby filling the remainder of the disc space.
  • the arthroscopic cannula and the application cannula are removed.
  • the flowable materials are further allowed to harden over 15 to 20 minutes.
  • the delivered biomaterial is allowed to cure, or cured by minimally invasive means and in such a manner that the cured biomaterial is retained in apposition to the prepared site.
  • the biomaterial can be cured by any suitable means, either in a single step or in stages as it is delivered. Once cured, the biomaterial surface can be contoured as needed by other suitable, e.g., endoscopic or arthroscopic, instruments. The joint is irrigated and the instruments removed from the portals.
  • interoperative x-rays are obtained to substantiate the preservation of the intervertebral disc space.
  • Direct observation of the intervertebral foramina for free cursing of the nerve rootlet is substantiated by visualization.
  • the retracted muscles are replaced and the local fascia is closed with interrupted absorbable suture.
  • the subcutaneous fascia and skin are then closed in the usual fashion.
  • the wound is then dressed.
  • a surgical procedure to fuse the vertebrae using methods and devices of the present invention can comprise the following steps:
  • a strut e.g. a balloon or a ramp having a partially annular shape
  • [0561] vii. Flow solutions laden with osteobiologic materials through the porous matrix, so that the osteobiologic materials collect in the pores.
  • the tube can also have a vacuum port to collect the eluted solution.
  • the result of this procedure is a formation of a fusion cage.
  • This procedure has numerous advantages. First, the resulting cage fills and supports the entire disc space, and so it is stable and is not prone to subsidence. Second, the minimally invasive treatment of the annulus fiborsus allows the resulting cage to be held in place by the retained annulus fibrosus. Third, the in situ formation of a scaffold eliminates the need in high impaction forces. Four, by the very nature of an inflatable device, it is adjusted to fit the desired disc height.
  • the precursor hydrogel is then poured into molds that are between 50-250 um in any dimension.
  • the precursor hydrogel is then cured, for example with a photoinitiator, to yield cell loaded hydrogel particles. These cell-hydrogel particles are then mixed with the viscous form of the hardenable material and injected as the osteobiologic composition.
  • each vertebral endplate of a patient has a 1500 mm cross-sectional area
  • the strut portion of the device will have a footprint of 20 areal % of the disc space.
  • the initial minimum strength required by the device may be decreased. If the OB composition is chosen to provide a 5 MPa strength and a 0.05 GPa modulus for at least 6-12 weeks in order to mimic cancellous bone, then the OB composition may share about 10% of the applied compressive load when the modulus of the strut is 2 GPa (assuming no annulus fibrosis). Therefore, the strength of the strut may be about 10% lower.
  • the devices of the present invention have a stiffness of at least 0.5 kN/mm. This lower preferred limit corresponds to the stiffness of conventional allograft cages. However, it is believed by some that the low stiffness of the allograft cages may sometime cause too much microfracture in the remodeling process. Therefore, in some embodiments, the stiffness of the devices of the present invention is preferably at least 5 kN/mm. Because it is believed that excessive device stiffness may undesirably cause stress shielding of the osteobiologic composition (and bone resorption), the stiffness of the device of the present invention is desirably no more than 50 kN/mm.
  • the stiffness of the device of the present invention is between 10 and 20 kN/mm. This range of values is comfortably between the range of stiffnesses found in conventional allograft cages (0.6-2.6 kN/mm) and CFRP cages (20-30 kN/mm). Accordingly, it is believed that the devices of the present invention will have stiffness appropriate for the support of bony fusion through the disc space.
  • stiffness of a component can be calculated as follows:
  • Comp.Modulus ( GPa ) ⁇ Area( mm 2 )/Disc Space Depth ( mm ) Stiffness ( kN/mm ) (7).
  • the initial minimum modulus required by the device may be decreased. If the OB composition is chosen to provide a 5 MPa strength and a 0.05 GPa modulus for at least 6-12 weeks in order to mimic cancellous bone, then the OB composition may share about 10% of the applied compressive load when the modulus of the strut is 2 GPa (assuming no annulus fibrosis). Therefore, the modulus of the strut may be about 10% lower.
  • the strut stiffness should be about 1 GPa. As noted above, the material reported by Timmer meets this requirement.
  • compositions suitable for use as load-bearing component of the present invention that include a fumarate-based polymer (such as polypropylene fumarate) cross-linked with a cross-linking agent containing a polypropylene fumarate-unit, such as polypropylene fumarate-diacrylate are disclosed in Timmer, Biomaterials (2003) 24:571-577 (hereinafter, “Timmer”), the entire teachings of which are incorporated herein by reference. These compositions are characterized by a high initial compressive strength (about 10-30 MPa) that typically increases over the first 12 weeks, high resistance to hydrolytic degradation (about 20-50 at 52 weeks), and an acceptable modulus for use as a strut (0.5-1.2 GPa).
  • a fumarate-based polymer such as polypropylene fumarate
  • a cross-linking agent containing a polypropylene fumarate-unit such as polypropylene fumarate-diacrylate
  • compositions suitable for use as resorbable cross-linkable component comprises those cross-linkable components disclosed by Wise in U.S. Pat. No. 6,071,982 (hereinafter, “Wise”), the entire teaching of which are herein incorporated by reference.
  • Exemplary absorbable elastomeric materials that allows resorbale devices to be delivered through the cannula are disclosed in U.S. Pat. No. 6,113,624 by Bezwada (hereinafter, “Bezwada), the entire teachings of which are incorporated herein by reference.
  • PCL is polycaprolactone
  • PLA is poly(lactic acid)
  • PPF is polypropylene fumarate
  • PMMA is polymethylmethacrylate
  • IPN interpenetrating networks
  • S-IPN or “Semi-interpenetrating networks” is a composition comprising a first cross-linkable polymer and a second non-cross-linkable polymer whrein, upon exposure to an appropriate cross-linking agent, the first cross-linkable polymer cross-links with itself, while the second polymer remains unaffected.
  • the Timmer IPN composition is chosen as the load bearing composition in the strut because it has sufficient initial and long term strength, acceptable modulus, and is resorbable.
  • the Timmer composition contains monomers, it is desirable to contain the composition in an inflatable device during curing. Since the Timmer composition is relatively resistant to degradation, the inflatable device can be made of a resorbable material having a short half life. Since the strut should also act as the distractor, the balloon should be non-compliant.
  • the Wise composition is chosen as the osteobiologic composition because is forms a scaffold having a strength and modulus essentially similar to that of cancellous bone. It can be infiltrated in-situ with a hydrogel containing osteogenic cells and osteoinductive growth factors.
  • the Wise composition contains monomers, it is desirable to contain the composition in an inflatable device during curing. Since bone in-growth is desirable through the region occupied by the balloon, the inflatable device should be made of a resorbable material having a very short half life (such as one day). Since the Wise composition a 25% expansion during pore formation, it would be desirable for the balloon to be compliant to allow the Wise composition conform to the disc space contour.
  • solid neat polycaprolactone is chosen as the load bearing composition in the strut because it has sufficient initial strength (15 MPa), is very resistant to degradation, has an acceptable modulus (0.5 GPa), and is resorbable.
  • the inflatable device need not be relatively resistant to degradation, and so can be made of a resorbable material having a short half life. Since the strut should also act as the distractor, the balloon should be non-compliant.
  • the Cooper composition is chosen as the osteobiologic composition because it is flowable at 40° C., and degrades sufficiently within a few months to form an hydroxyapatite based-scaffold. Because of its low delivery temperature, certain dimer bone morphogenetic proteins can also be delivered during the injection of this composition.
  • the inflatable device should be made of a resorbable material having a very short half-life (such as one day).
  • the polycaprolactone S-IPN composition (as reported in Hao) is chosen as the load bearing composition in the strut because it may have mechanical properties about 3-6 fold greater than neat polycaprolactone, and is resorbable.
  • the polycaprolactone-polycaprolactone composition contains monomers, it is desirable to contain the composition in an inflatable device during curing. Since the polycaprolactone composition is relatively resistant to degradation, the inflatable device can be made of a resorbable material having a short half life. Since the strut should also act as the distractor, the balloon should be non-compliant.
  • CaPO 4 is chosen as the load bearing composition in the strut because it has sufficient initial and long term strength, acceptable modulus, and is resorbable.
  • the inflatable device need be relatively resistant to degradation, and so should be made of a resistant material that can contain the CaPO 4 for at least one year. Since the strut should also act as the distractor, the balloon should be non-compliant.
  • One material that is resistant and non-compliant is polyetherether ketone.
  • the CaPO 4 composition is chosen as the osteobiologic composition because it is flowable at body temperature, and degrades sufficiently within a few months to form an hydroxyapatite based-scaffold. Because of its delivery at body temperature, hydrogels containing temperature sensitive additives, such as osteogenic cells and osteoinductive components (such as bone morphogenetic proteins), can also be delivered during the injection of this composition.
  • the Wise composition is chosen as the load bearing composition in the strut because it has sufficient initial strength, acceptable modulus, and is resorb able.
  • the inflatable device need be relatively resistant to degradation, and so should be made of a resistant material that can contain the Wise Composition for at least one year. Since the strut should also act as the distractor, the balloon should be non-compliant.
  • One material that is resistant and non-compliant is polyetherether ketone.
  • the Mikos composition is chosen as the osteobiologic composition because it is injectable at body temperature, forms an in-situ scaffold in which hydrogels containing temperature sensitive additives, such as osteogenic cells and osteoinductive components (such as bone morphogenetic proteins), can be delivered.
  • temperature sensitive additives such as osteogenic cells and osteoinductive components (such as bone morphogenetic proteins)
  • CaPO 4 is chosen as the load bearing composition in the strut because it has sufficient initial and long term strength, acceptable modulus, and is resorbable.
  • the inflatable device need be relatively resistant to degradation, and so should be made of a resistant material that can contain the CaPO 4 for at least one year. Since the strut should also act as the distractor, the balloon should be non-compliant.
  • One material that is resistant and non-compliant is polyetherether ketone.
  • the polylactic acid beads are chosen as the matrix of the osteobiologic composition because they can be packed into the disc space at body temperature and heat bonded with hot water to form an in-situ formed scaffold. If the beads are selected to have a 2 mm diameter, the porosity of the resulting scaffold will be about 40 vol % with a pore size of about 500 um. Hydrogels containing temperature sensitive additives, such as osteogenic cells and osteoinductive components (such as bone morphogenetic proteins), can then be delivered the in-situ scaffold.
  • the packed beads must be packed into the disc space and then heat bonded with a high temperature fluid, it may be desirable to contain both the beads and the hot fluid in a balloon.
  • Nitonol reinforced balloon is desirable because the reinforcements can help the balloon withstand the high pressures needed during packing.
  • Timmer polypropylene fumarate-polypropylene fumarate-diacrylate with tricalcium phosphate (Embodiment B) with 50 vol % porosity (or seeded hydrogel phase) will still have a 25 MPa compressive strength after one year. If it takes the whole disc space, only 11.3 MPa is required. 2 ⁇ safety factor.

Abstract

An orthopedic device for implanting between adjacent vertebrae comprising: an arcuate balloon and a hardenable material within said balloon.
In some embodimnents, the balloon has a footprint that substantially corresponds to a perimeter of a vertebral endplate. An inflatable device is inserted through a cannula into an intervertebral space and oriented so that, upon expansion, a natural angle between vertebrae will be at least partially restored. At least one component selected from the group consisting of a load-bearing component and an osteobiologic component is directed into the inflatable device through a fluid communication means.

Description

    RELATED APPLICATIONS
  • This application claims the benefit of U.S. Provisional Application No. 60/448,221, filed on Feb. 14, 2003. The entire teachings of the above application is incorporated herein by reference.[0001]
  • BACKGROUND OF THE INVENTION
  • A leading cause of lower back pain arises from lumbar intervertebral disc pathology, including rupture or degeneration of the disc. Radicular pain in the lower extremities may be caused by the compression of spinal nerve roots by a bulging disc. Additionally, lower back pain may be caused by collapse of the disc and the dysarthrosis of an unstable or degenerative vertebral facet joint. One proposed method of managing these problems is to remove the problematic disc and replace it with a porous device that restores disc height and allows for bone growth therethrough for the fusion of the adjacent vertebrae. These devices are commonly called “fusion devices.”[0002]
  • Intervertebral body fusion devices typically must carry extremely high loads (on the order of 1-4 kN) for a period of several months, or until fusion occurs. Accordingly, a fusion device or bone graft substitute designed for promoting bony fusion at another location in the body (such as long bone fusion) may not be suitable for use as an intervertebral body fusion device. For example, many bony fusion devices disclose the use of a gel such as a hydrogel as the structural carrier for an osteoinductive or an osteogeneic component. However, such gels typically do not posses the stiffness or mechanical strength found to be required for lumbar intervertebral fusion devices. [0003]
  • In general, delivery of conventional intervertebral fusion devices has required significantly invasive implantation procedures. Open surgical implantation of posterior implants requires excision of stabilizing muscles, ligaments, tendons, and bony structures such as the facet joints. The implants must not only overcome the destabilization caused by the surgical procedure, but must add the extra stability needed to promote bony fusion. Open anterior surgery in the lumbar spine is very risky due to the close proximity of sensitive vascular structures, such as the aorta and bifurcation of the aorta. Furthermore, the anterior open procedure can cause significant scar formation on the spine, making anterior revision surgery, if necessary, even more risky. [0004]
  • Minimally invasive procedures have been developed to help mitigate these problems. However, current techniques require appreciable surgical expertise and can significantly increase surgery time. Furthermore, insertion of interbody fusion cages through minimally invasive means often requires high insertion forces. [0005]
  • A number of such prosthetic implants have been described for serving as an intervertebral disc, or nucleus pulposus, replacement, involving the delivery of prosthetic materials through a small diameter cannula no larger than is needed to perform an adequate discectomy. Therefore, the injectable prosthetic devices are typically delivered in a first fluid form and then harden to a second form once inside the disc space to span the disc space height and preferably fill the disc space following discectomy. However, the requirements for a bone fusion system are very different from those of injectable prosthetic devices. [0006]
  • In summary, there is a need for an intervertebral strut injectable into the disc space that can create or maintain a preferred spatial relationship between adjacent vertebral body endplates (curvature and distraction) and comprises an osteogenic component to promote bony fusion between the two adjacent vertebra. [0007]
  • SUMMARY OF THE INVENTION
  • The present invention relates to a device for intervertebral spinal fusion and method of making thereof. [0008]
  • In one embodiment, the present invention is an orthopedic device for implanting between adjacent vertebrae comprising a generally arcuate balloon and a hardenable material within said balloon. [0009]
  • In another embodiment, the present invention is an intervertebral spinal fusion device comprising at least one arcuate inflatable balloon whereby at least partially filling the balloon between two adjacent vertebrae at least partially restores a natural angle between the adjacent vertebrae, and wherein said arcuate balloon contains a load-bearing component within a lumen defined by the balloon. [0010]
  • In another embodiment, the present invention is an intervertebral spinal fusion device comprising a anterior frame having an upper inflatable rim and a lower inflatable rim, and a rigid inflatable posterior frame attached to the upper and lower inflatable rims of the anterior frame. The anterior frame is detachably connected to the first fluid communication means. The posterior frame is detachably connected to the second fluid communication means. Upon at least partially filling the upper and lower inflatable rims and the posterior frame between two adjacent vertebrae, a natural angle between said vertebrae is at least partially restored. [0011]
  • In another embodiment, the present invention is a method of implanting an intervertebral spinal fusion device, comprising the steps of (a) performing a discectomy while preserving an outer annular shell; (b) inserting an inflatable device that includes a deflated arcuate balloon into an intervertebral space; (c) directing an osteobiologic omponent into the deflated arcuate balloon in an amount sufficient to inflate the balloon and distract the disc space. [0012]
  • In another embodiment, the present invention is a method of implanting an intervertebral spinal fusion device, comprising the steps of (a) inserting an inflatable device through a cannula into an intervertebral space, said inflatable device including an arcuate balloon connected to at least one fluid communication means, wherein said inflatable device upon expansion between two adjacent vertebrae at least partially restores a natural angle between the adjacent vertebrae; (b) orienting said inflatable device so that upon expansion a natural angle between vertebrae will be at least partially restored; (c) directing a load-bearing component into the inflatable device through the fluid communication means. [0013]
  • In another embodiment, the present invention is a method of at least partially restoring a natural angle between two adjacent vertebrae, comprising the steps of (a) inserting an inflatable device through a cannula into an intervertebral space; (b) orienting said inflatable device so that upon expansion of the device a natural angle between vertebrae will be at least partially restored; and (c) expanding said inflatable device by directing a load-bearing component into said inflatable device. [0014]
  • In another embodiment, the present invention is a method of delivering an osteobiologic material comprising (a) inserting an inflatable device into an intervertebral space wherein at least a portion of the device upon expansion has a substantially toroidal shape thereby forming an open cavity defined by an outer surface of the toroidal shape and having an axial dimension and a radial dimension; (b) orienting at least a portion of the device so that so that the axial dimension of the open cavity is substantially parallel to a major axis of a spinal column of a patient in which the device has been implanted; (b) inflating said inflatable device by directing a load-bearing component into said inflatable device; (c) directing an osteobiologic material into the open cavity, said material including at least one water-soluble material; (d) directing an aqueous fluid into into the open cavity defined by the inflated device thereby dissolving at least one said water-soluble material, and forming a porous matrix; and (e) delivering additional osteobiologic component into the porous matrix in the amount sufficient to fill at least 90% of the porous matrix by volume. [0015]
  • In another embodiment, the present invention is a pharmaceutical composition comprising a pharmaceutically acceptable carrier or diluent and (a) at least one polymer flowable between 38° C. and 45° C. selected from the group consisting of homopolymers of poly(ε-caprolactone), poly(p-dioxanone), or poly(trimethylene carbonate) or copolymers or mixtures thereof, or copolyesters of p-dioxanone or trimethylene carbonate and glycolide or lactide or mixtures thereof, and in particular, copolymers of p-dioxanone/glycolide, p-dioxanone/lactide, trimethylene carbonate/glycolide and trimethylene carbonate/lactide, or copolyesters of .epsilon.-caprolactone and glycolide or mixtures thereof, or mixtures of homopolymers of ε-caprolactone and lactide; and (b) at least one growth factor resistant to denaturing at at least about 45° C. selected from the group consisting of bone morphogenetic proteins. [0016]
  • In another embodiment, the present invention is an intervertebral fusion device comprising an in-situ formed osteobiologic component comprising (a) a matrix having an internal surface defining an open porosity suitable for bone growth therethrough, and (b) an osteogenic component located within the open porosity. [0017]
  • In another embodiment, the present invention is an intervertebral fusion device for providing bony fusion across a disc space, comprising (a) a strut having a upper surface for bearing against the upper endplate and a lower surface for bearing against the lower endplate, and (b) an in-situ formed osteobiologic component. [0018]
  • In another embodiment the present invention is an intervertebral fusion device for providing bony fusion across a disc space, comprising a strut comprising (a) an upper surface for bearing against the upper endplate, (b) a lower surface for bearing against the lower endplate, and (c) an injectable load bearing composition disposed between the upper and lower surfaces. [0019]
  • In another embodiment, the present invention is an intervertebral fusion device comprising a matrix having an internal surface defining an open porosity suitable for bone growth therethrough, wherein the matrix is formed by a plurality of in-situ bonded beads. [0020]
  • In another embodiment, the present invention is an intervertebral fusion device comprising a strut comprising (a) a first component comprising (i) a lower bearing surface adapted for bearing against a lower vertebral endplate, and (ii) an upper surface comprising a leading end, an angled middle portion and a trailing end; and (b) a second component comprising (i) an upper bearing surface adapted for bearing against an upper vertebral endplate and (ii) an upper surface comprising a leading end, an angled middle portion and a trailing end. The angled portion of the first component mates with the angled portion of the second component. [0021]
  • In another embodiment, the present invention is a kit for providing interbody fusion across an intervertebral disc space, comprising (a) a cannula defining an inner diameter; (b) a hardenable material capable of supporting intervertebral load; and (c) a flowable osteobiologic composition. [0022]
  • In another embodiment, the present invention is an intervertebral fusion device for providing bony fusion across a disc space, comprising (a) a strut having a upper surface for bearing against an upper endplate and a lower surface for bearing against a lower endplate, the upper surface and lower surface defining a height therebetween, and (b) an in-situ formed osteobiologic component. The height of the strut is no greater than the height of the disc space. [0023]
  • In another embodiment, the present invention is a method of providing interbody fusion across an intervertebral disc space, comprising the steps of (a) providing a cannula defining an inner diameter; (b) moving a load bearing composition through the cannula and into the disc space to form a in-situ formed load bearing strut; and (c) moving an osteobiologic composition through the cannula and into the disc space to form an in-situ formed osteobiologic composition. [0024]
  • In another embodiment, the present invention is an intervertebral fusion device for providing bony fusion across a disc space, comprising a strut comprising (a) an upper surface for bearing against the upper endplate and (b) a lower surface for bearing against the lower endplate. The strut comprises an in-situ formed load bearing composition. [0025]
  • In another embodiment, the present invention is an intervertebral fusion device for providing bony fusion across a disc space, comprising a strut comprising (a) an upper surface for bearing against the upper endplate, (b) a lower surface for bearing against the lower endplate, and (c) an in-situ formed load bearing composition disposed between the upper and lower surfaces. [0026]
  • In another embodiment the present invention is an intervertebral fusion device comprising (a) a strut have a shape memory and comprising (i) an upper surface for bearing against the upper endplate, (ii) a lower surface for bearing against the lower endplate, and (b) an in-situ formed osteobiologic component. [0027]
  • In another embodiment, the present invention is an intervertebral fusion device comprising (a) a strut comprising an upper surface for bearing against the upper endplate and a lower surface for bearing against the lower endplate, and (b) an in-situ formed osteobiologic component comprising a matrix component having an internal surface defining a scaffold having open porosity suitable for bone growth therethrough, and an osteogenic component located within the open porosity. [0028]
  • In another embodiment, the present invention is an intervertebral fusion device comprising a strut comprising an upper surface for bearing against the upper endplate and a lower surface for bearing against the lower endplate, and an in-situ formed osteobiologic component comprising an injectable matrix component, an an osteoinductve component embedded within the matrix. [0029]
  • In another embodiment, the present invention is an intervertebral fusion device comprising a strut comprising an upper surface for bearing against the upper endplate a lower surface for bearing against the lower endplate, and an in-situ formed osteobiologic component comprising an injectable matrix component, and a porogen embedded within the matrix. [0030]
  • In another embodiment, the present invention is an intervertebral fusion device comprising a strut comprising an upper surface for bearing against the upper endplate, a lower surface for bearing against the lower endplate, and an in-situ formed osteobiologic component comprising an expandable device defining a cavity, and an injectable osteobiologic composition located within the cavity. [0031]
  • In another embodiment, the present invention is an intervertebral fusion device comprising a strut comprising an expandable device having a cavity, an upper surface for bearing against the upper endplate, a lower surface for bearing against the lower endplate, and an inner wall defining a through hole and an injectable load bearing composition located within the cavity, and an osteobiologic component located in the throughhole. [0032]
  • In another embodiment, the present invention is an intervertebral fusion device comprising a strut comprising an upper surface for bearing against the upper endplate, and a lower surface for bearing against the lower endplate; and an in-situ formed osteobiologic component comprising an injectable, matrix component essentially free of monomer. [0033]
  • In another embodiment, the present invention is an intervertebral fusion device for providing bony fusion across a disc space, comprising a strut comprising (a) an upper surface for bearing against the upper endplate, (b) a lower surface for bearing against the lower endplate, and (c) an in-situ formed load bearing composition disposed between the upper and lower surfaces and made of a material comprising a cross-linked resorbable polymer. [0034]
  • The advantages of the present invention are numerous. One advantage is that the present invention makes possible minimally invasive surgical procedures to restore a natural angle and increase disc height between two adjacent vertebrae. Furthermore, the same device used used to create distraction/lordosis can function as the intervertebral implant needed to maintain height and natural angle. Another advantage is that the present invention makes possible a minimally invasive procedure to create in situ a structural scaffold filled with osteoinductive materials.[0035]
  • BRIEF DESCRIPTION OF THE DRAWINGS
  • FIG. 1 is a plot of strength over time of a resorbable polymer and bone growth. [0036]
  • FIGS. [0037] 2(a) through 2(e) are schematic representations of preferred embodiments of a semicircular, circular, bilateral and generally crescent, arcuate, or toroidal shapes of the device of the present invention.
  • FIGS. [0038] 2(f) and 2(g) show a perspective and a top view, respectively, of a preferred embodiment of a device of the present invention.
  • FIG. 3([0039] a) and FIG. 3(b) show a perspective and a top view, respectively, of a preferred method of the introduction of a cannula into the disc space.
  • FIG. 4([0040] a) and FIG. 4(b) show a perspective and a top view, respectively, of a preferred method of the deployment of an inflatable device into the disc space through the cannula.
  • FIG. 5([0041] a) and FIG. 5(b) show a perspective and a top view, respectively, of an embodiment of the present invention wherein the device comprises a generally toroidal balloon and the osteobiologic component is injected into an open cavity defined by the outer surface of the generally toroidal balloon.
  • FIG. 6([0042] a) and FIG. 6(b) show a perspective and a top view, respectively, of an embodiment of the present invention comprising more than one balloon.
  • FIG. 7([0043] a) and FIG. 7(b) show a perspective and a top view, respectively, of another embodiment of the present invention comprising more than one balloon.
  • FIG. 8([0044] a) and FIG. 8(b) show an embodiments of the present invention comprising an arcuate inflatable balloon with reinforced walls.
  • FIGS. [0045] 9(a) through (d) show an embodiment of an inflatable device and a method of inserting an inflatable device of the present invention into the disc space, wherein a pair of semi-circular flexible members is used for guiding the device.
  • FIGS. [0046] 10(a) and 10(b) represent plan and lateral views, respectively, of an embodiment of an inflatable device of the invention whereby a pair of semi-circular flexible upper and lower wall components, which can be used for guiding the device, are joined by an inflatable balloon.
  • FIGS. [0047] 11(a) and (b) show an embodiment of the present invention wherein the device comprises four semi-circular flexible components for guiding the inflatable device into the disc space.
  • FIGS. [0048] 12(a) and (b) show another embodiment of device of the present invention that includes guiding members.
  • FIGS. [0049] 13(a) through (d) shows a preferred embodiment of the method of the present invention. FIG. 13(a) and FIG. 13(b) show inserting a cannula into an intervertebral space, followed by inserting an inflatable balloon of a generally toroidal shape into an intervertebral space through the cannula. The balloon is expanded by directing a load-bearing component into said balloon. FIG. 13(c) shows injecting an osteobiologic component comprising a water-soluble component into an open cavity, defined by the outer surface of the balloon, and FIG. 13(d) shows dissolving the water-soluble component.
  • FIGS. [0050] 14(a) and (b) show a top and a lateral view, respectively, of another embodiment of a device of the present invention employing a ramp.
  • FIG. 14([0051] c) is a cross section of the device of FIGS. 14(a) and (b).
  • FIG. 14([0052] d) is a perspective view of the device of FIGS. 14(a)-(c).
  • FIG. 15 shows one embodiment of a method of deployment of the device of FIGS. [0053] 14(a)-(d).
  • FIG. 16 shows another embodiment of a mthod of deployment of the device of FIGS. [0054] 14(a)-(d).
  • FIGS. [0055] 17(a) and (b) show a particularly preferred embodiment of the device of the present invention in collapsed and expanded configuration, respectively.
  • DETAILED DESCRIPTION OF THE INVENTION
  • The present invention relates to a vertebral fusion device for simultaneously distracting two adjacent vertebral bodies and delivering a flowable material into a disk space. As used herein, the term “vertebral fusion” refers to a medical procedure that results in maintaining separation between vertebrae. In one embodiment, vertebral fusion provides for bony ingrowth that fixes two adjacent vertebrae in a desired, for example, distracted and/or angulated, position. [0056]
  • In a preferred embodiment, a natural angle between two adjacent vertebral plates is replicated by fusing the two adjacent vertebrae. As used herein, the “natural angle” refers either to natural lordosis or to natural kyphosis. The angle can be positive, negative or zero (i.e., when the opposing surfaces of the adjacent vertebrae are essntially coplanar). In one embodiment, a natural lordosis is replicated or restored. As used herein, the term “natural lordosis” refers to a natural angle between two adjacent vertebral plates within the lumbar or cervical spine segments wherein the distance between the anterior portions of the two adjacent vertebral plates is not smaller than the distance between the posterior portions of the two adjacent vertebral plates. In another embodiment, a natural kyphosis is replicated or restored. As used herein, the term “natural kyphosis” refers to a natural angle between two adjacent vertebral plates within the thoracic spine segment wherein the distance between the anterior portions of the two adjacent vertebral plates is not geater than the distance between the posterior portions of the two adjacent vertebral plates. [0057]
  • In another embodiment of vertebral fusion, a fusion means maintains the separation between the vertebrae. Preferably, the fusion means at least partially restore the natural function of nucleus pulposis by permitting relative freedom of movement while substantially maintaining the separation between the vertebrae. [0058]
  • The components of the device comprise at least one member selected from the group consisting of a load-bearing component and an osteobiologic component. Preferably, both components are used. In some embodiments, load-bearing component includes osteobiologic component. As used herein the term “load-bearing” component or material refers to any material capable of supporting vertebrae in distracted position. The load-bearing component can include a hardenable material or a noncompressible fluid contained within an inflatable balloon. The terms “strut” refers to any part, portion or component of the device, including a flowable material, that either alone or in combination with other parts, portions or components of the device is capable of supporting vertebrae in distracted position. Examples of a strut include a hardened flowable material, a balloon with rigid walls and an inflatable balloon or bag filled with a hardenable material or a noncompressible fluid. The purpose of the strut is to bear the high spinal loads. In addition, the strut can be used to increase the disc space height and/or at least partially restore or create natural curvature of the spinal region being fused. Increasing disc height is often critical for decompressing nerve roots and restoring or creating healthy spine curvature is important for preventing accelerated degeneration of adjacent intervertebral discs. The term “arcuate” refers to a shape having curvature roughly corresponding to the perimeter of a vertebral endplate, but does not include enclosed rings or generally annular structures. [0059]
  • As used herein, the “osteobiologic” component or material refers to any material that can induce and/or support existing or new bone growth. In some embodiments, the load-bearing material includes osteobiologic material. For example, a material comprising bone growth factors or mesynchemal stem cells is an osteobiologic component. Osteobiologic component can further include either one or both an osteoinductive component and an osteoconductive component. As used herein, the “osteoinductive” component or material refers to any material that can induce bone growth. Preferably, osteoinductive components includes signal molecules required to induce the osteoprogenitor cells to form new bone. Examples of osteoinductive components are bone morphogenetic proteins (BMP's), growth differentiation factors (GDF's) and transforming growth factors (TGF). As used herein, the “osteoconductive” component or material refers to any material that can provide support for bone growth subsequent to induction. Examples of osteoconductive components include natural collagen-based materials including bone, and synthetic porous resorbable polymers and ceramics. [0060]
  • Generally, the present invention relates to in situ formed intervertebral fusion devices. Preferably, the components of the in situ formed device can be delivered percutaneously (e.g., through a cannula having a diameter of no more than 5 mm, preferably no more than 2 mm). However, the precursor components of the in-situ formed device can also be delivered in cannulae of much larger dimension (such as up to 18 mm, or through a Craig needle). More preferably, the components of the in-situ formed device are delivered into the disc space in the form of injectable compositions. [0061]
  • For the purposes of the present invention, the term “in situ formed” refers to any material that is delivered into the disc space in a first form and takes on a different form after placed in the disc space. In some embodiments, “in situ formation” includes delivering a viscous fluid into the disc space and hardening that fluid. In some embodiments, “in situ formation” includes delivering discrete components into the disc space and bonding (preferably, heat bonding or by reaction) together those components. In some embodiments, “in situ formation” includes delivering discrete components into an opening in an inflatable device located in the disc space and preventing their escape from the inflatable device by closing off the opening of the inflatable device. In some embodiments, “in situ formation” includes delivering discrete components into the disc space and assembling together those components within the disc space. [0062]
  • In situ formation” excludes simply packing particles such as autograft or allograft particles into the disc space, as well as simply delivering a gel into the disc space. [0063]
  • Without being limited to any particular theory, it is believed that in conventional fusion systems, there is often a race between implant degradation and bone growth. Now referring to FIG. 1, the hypothetical strength profiles of a conventional resorbable implant (dotted line) and of the bone that replaces the implant (solid line) are provided. For the purpose of explaining FIG. 1, the strength of the system is defined as the lesser of the strength of the resorbable implant and the strength of the healing bone. It then follows that between the time of the surgical procedure (T[0064] 0) and the time for complete bone healing to take place (TF), the load applied to the system must never be above the strength of the system at point C (shown as SC). It is known in the art that the maximum in vivo average daily living load on the human lumbar spine is approximately 4,000 N. Assuming that this is the maximum load to be experienced by the system, then the system strength should not fall below 4,000 N.
  • Because the strut can be made relatively strong (e.g., capable of supporting about 15 kN in axial compression), even when the load applied to the system is relatively high, the strength of the system will still be sufficient to support the disc space and fusion will occur. Once sufficient bone growth through the osteobiologic component occurs, the strut may degrade without endangering support of the disc space. [0065]
  • To summarize, the strut supports the disc space while the osteobiologic composition grows bone. [0066]
  • In preferred embodiments, the strut of the present invention acts in a manner similar to the cortical rim of a vertebral body. Desirable features for the load bearing composition of the strut are as follows: [0067]
  • a) sufficient strength to bear the typical loads borne by vertebral bodies; [0068]
  • b) stiffness similar to that of cortical bone (or, in relatively thick embodiments, cortico-cancellous bone); [0069]
  • c) degradation resistance (e.g., capable of bearing at least 15 MPa, preferably at least 25 MPa) for at least one year, preferably at least 18 months; [0070]
  • d) resorbability. [0071]
  • Accordingly, in one embodiment, the present invention is an intervertebral spinal fusion device comprising a resorbable load-bearing material wherein the combination of the resorbable load-bearing material and the new bone growth provides a load-carrying capacity that is at least sufficient to support spinal load. Preferably, the load-bearing material includes or is supplemented by an osteobiologic component. In another embodiment, the present invention is a method of making an intervertebral fusion device comprising selecting a resorbable load-bearing material wherein the combination of the resorbable load-bearing material and the new bone growth provides a load-carrying capacity that is at least sufficient to support spinal load. [0072]
  • In one embodiment, the strut should have a size sufficient to provide a footprint covering between about 3% and about 40% of the area of the corresponding vertebral endplate. Preferably, the strut foot covers between about 10% and about 30%, more preferably between about 10% and about 20% of the corresponding vertebral endplate. [0073]
  • In some embodiments, in which the osteobiologic component contains at least one of a) a growth factor and b) an osteogenic component, e.g. a source of cells (such as stem cells), it is believed that the strut footprint can be in the range of about 10% to about 20% of the disc space. This is because it is believed that these additives sufficiently shorten the time to fusion so that the danger of strut subsidence is sufficiently low. Similarly, in some embodiments, in which the osteobiologic component contains both a) a growth factor and b) stem cells, it is believed that the strut footprint can be in the range of about 5% to about 10% of the disc space. [0074]
  • It is further believed that providing the osteobiologic component with both a) a growth factor and b) stem cells provides further desirable design options. These additives may also reduce or eliminate the need for posterior or supplemental fixation. Currently posterior fixation is generally thought to be highly desirable to achieve a fusion success in the interbody space. In some embodiments, the provision of effective amounts of such additives can increase the speed for fusion so as to render superfluous the posterior or supplemental fixation, and patients would no longer need to endure a more invasive pedicle screw procedure to apply the stability needed for fusion. [0075]
  • In some embodiments, the device can comprise a balloon of semicircular, circular, bilateral (comprising more than one balloon) and generally toroidal shape. Preferred embodiments and positions of a device of the present invention on an [0076] endplate 8 of a vertebra 10 are shown in FIGS. 2(a) through (e). Now referring to FIG. 2(a), this shape allows the balloon 12 to essentially cover at least the anterior periphery 14 of the corresponding vertebral endplate 8, and thereby bear a substantial portion of the spinal load. This shape further allows the surgeon to first place the device in place and then fill the remaining portion of the disc space with, for example, an osteobiologic component.
  • In other embodiments, as in FIG. 2([0077] b), the balloon 12 has a quasi-circular shape. This device has the advantage of providing even more of a load-bearing footprint than the embodiment of FIG. 2(a), and also substantially prevents unwanted leakage of the osetobiologic component during subsequent filling of an open cavity defined by an outer surface of the balloon.
  • Now referring to FIG. 2([0078] c), in some embodiments, the device comprises two balloons 12 that can be used to support the vertebral load. The use of two balloons allows a surgeon to evenly support the load on each side of the endplate 8.
  • Now referring to FIG. 2([0079] d), in some embodiments, the balloon 12 has a generally toroidal (“banana”) shape. The banana shape allows the surgeon to put in place a single device preferably on the anterior half 14 of the disc space. In other embodiments, the strut has the footprint of a banana cage such as that described in Attorney Docket #DEP 5012, “Novel Banana Cage”, filed Dec. 31, 2002, U.S. Ser. No. 10/334,599, the specification of which is incorporated by reference in its entirety.
  • Now referring to FIG. 2([0080] e), in some embodiments, the strut 12 is introduced translaterally so as to form a single ramp stretching essentially transversely across the endplate 8. This design in advantageous when used in a posterolateral approach of surgery, as this approach takes advantage of the fact that the muscle planes in the vicinity of the approach allow the implant to be delivered in a less invasive manner.
  • Now referring to FIG. 2([0081] f), in a preferred embodiment, the device 12 of the present invention has a substantially semiannular footprint. The device 12 is placed on the anterior portion of the endplate 8 of a vertebra 10 so that height D of a anterior portion of the device is equal or greater than height h of a posterior portion of the device 12. Referring to FIG. 2(g), the device 12 defines an internal radius ri, an external radius re and thickness t. In one embodiment, illustrated in FIG. 2(g), ri is approximately about 22 mm, re is approximately about 25 mm and t is approximately about 3 mm.
  • In preferred embodiments, the height of the strut is at least 90%, and preferably at least equal to, the height of the natural disc space. This allows the surgeon to distract the disc space and restore at least a portion of the disc height. In some embodiments, the height of the strut is greater than that of the natural disc space. [0082]
  • As used herein the word “distraction” will refer to the separation of joint surfaces to a desired extent, without rupture of their binding ligaments and without displacement. Distraction can be accomplished by any suitable means, for example mechanical or hydrostatic means. Mechanical means can include, for instance, attaching hooks or jacks to the bony endplates and using those hooks or jacks to separate the bones. Optionally, the surgeon can employ external traction. In one embodiment, an in-situ foaming material is used as a distraction device. Other means include, for example, hydrostatic means, e.g., by pressurized injection of the biomaterial itself. By the use of distraction, the disc space can be sufficiently re-established to achieve any desired final dimensions and position. Optionally, and preferably, the means used to accomplish distraction also serves the purpose of forming one or more barriers (e.g., balloons) for the flowable load bearing strut material. [0083]
  • The disc space can be distracted prior to and/or during either a discectomy itself and/or delivery of a flowable biomaterial. A constricted disc space is generally on the order of 3 to 4 mm in height. Suitable distraction means are capable of providing on the order of about 3 atmospheres to about 4 atmospheres, (or on the order of about 40 psi to about 60 psi) in order to distract that space to on the order of 8 to 12 mm in height. [0084]
  • In one embodiments, the strut has a wedged shape so that the height of the anterior portion of the expanded device is greater than the height of the posterior portion of the expanded device. This allows the surgeon to restore lordosis when the interbody fusion device is used in either the lumbar or cervical regions of the spine. Preferably, the wedged shape produces an angle of between 5 and 20 degrees, more preferably between 5 and 15 degrees. [0085]
  • In another embodiment, the strut has a wedged shape so that the height of the anterior portion of the expanded device is smaller than the height of the posterior portion of the expanded device. This allows the surgeon to restore kyphosis when the interbody fusion device is used in thoracic regions of the spine. Preferably, the wedged shape produces an angle of between 5 and 20 degrees, more preferably between 5 and 15 degrees. [0086]
  • In preferred embodiments, the height of the medial portion of the strut is greater than the height of the lateral portion of the expanded device. This geometry more closely mimics the natural doming of the disc space. [0087]
  • With the injectable device of the present invention, there is provided a “custom” implant formed to the anatomy of the patient's endplates. The provision of a conformable implant may provide a faster and more consistent fusion. [0088]
  • In some embodiments, the annulus fibrosus can itself serve as a suitable mold for the delivery and solidification of either the flowable load-bearing material (in one embodiment) or the osteobiologic component (in another embodiment). Free injection may optimize the extent to which the injectable device conforms to the contour of the disc space, thereby enhancing resistance to retropulsion. Optionally, the interior surface of the annulus fibrosus can be treated or covered with a suitable material in order to enhance its integrity and use as a mold. [0089]
  • In some embodiments, at least one of the flowable materials is delivered into an inflatable device (such as a balloon) previously placed in the disc space. [0090]
  • In some embodiments, the load bearing composition is delivered into an inflatable device (such as a balloon) previously placed in the disc space. Now referring to FIGS. [0091] 3(a) and (b), in one preferred method, a cannula 18, having an inner diameter of no more than 6 mm, is inserted into the disc space. Next, and now referring to FIGS. 4(a) and (b), the inflatable device 12 is deployed through the exit opening of the cannula 18 and the flowable load bearing composition is introduced into the inflatable device at a pressure and volume suitable to expand the inflatable device and distract the disc space.
  • The fixed shape of the expanded device allows the surgeon to predetermine the shape of the flowable material and simply fill the device with the flowable material. The device substantially prevents unwanted flow of the material. The prevention of unwanted flow desirably prevents the material from damaging important surrounding structures such as the spinal cord, aorta and vena cava. Also, the inflatable device can be tailored to fill any portion of the disc space. [0092]
  • Further, the present inventors believe that inclusion of an inflatable balloon in a strut can assure that the opposing trends of degradation of bioabsorbable materials and new bone growth will result in fusion of the vertebrae in a position approximating the natural angle between two adjacent vertebrae. If the balloon is made of a resorbable, water-impermeable material, the balloon will effectively shield the load-bearing composition from water during the initial stages of fusion and so delay the onset of hydrolysis and degradation of the load-bearing material. Preferably, the balloon begins to degrade within about 1-2 months after fusion of the osteobiologic composition, thereby allowing the load-bearing material it contains to slowly degrade and grow bone. [0093]
  • In some preferred embodiments, the distraction of the disc space is accomplished by an inflatable, yet rigid, balloon or bladder. The balloon can be delivered in deflated form to the interior of the annulus and there inflated in order to distract the disc space and provide a region for the delivery of biomaterial. The balloon is preferably of sufficient strength and of suitable dimensions to distract the space to a desired extent and to maintain the space in distracted position for a period of time sufficient for the biomaterial to be delivered and, optionally, to harden. [0094]
  • One of the primary functions of the balloon is to influence or control the shape of the hardenable material, following injection therein. The implantable balloon is not normally required to restrain pressure over an extended period of time. Thus, a greater design flexibility may be permitted, as compared to conventional angioplasty or other dilatation balloons. For example, the balloon may be porous, either for drug delivery as has been discussed, or to permit osteoincorporation and/or bony ingrowth. [0095]
  • In one particularly preferred embodiment, there is provided a method for fusing an intervertebral disc space, comprising the steps of: [0096]
  • a) using microsurgical techniques to perform a discectomy while preserving an outer annular shell; [0097]
  • b) inserting a deflated balloon into the disc space; [0098]
  • c) injecting a flowable load bearing composition into the deflated balloon (preferably, in an amount sufficient to distract the disc space), and [0099]
  • d) solidifying the flowable strut material. [0100]
  • In one particularly preferred embodiment, there is provided a method for fusing an intervertebral disc space, comprising the steps of: [0101]
  • a) using microsurgical techniques to perform a discectomy while preserving an outer annular shell, [0102]
  • b) inserting a deflated balloon having peripheral struts into the disc space, [0103]
  • c) injecting an osteobiologic component into the deflated balloon in an amount sufficient to inflate the balloon and distract the disc space with the strut component of the balloon. [0104]
  • Optionally, and preferably, the space is distracted by the use of one or more suitable insertable or inflatable devices, e.g., in the form of inflatable balloons. When inflated, such balloons provide rigid walls (e.g., fiber supported) that are sufficiently strong to distract the space. An inflatable device providing sufficient strength and dimensions can be prepared using conventional materials. In one embodiment, the uninflated balloon can be delivered to the center of the annular shell, and there inflated to expand the annular shell and in turn, distract the space. In another embodiment, the uninflated balloon can be delivered to the anterior rim of the annular shell, and there inflated to provide a cavity for the injection of the load bearing flowable material. Preferably, the load bearing composition is injected in an amount sufficient to distract the space. [0105]
  • The inflatable device can be delivered to the disc space by any suitable means, e.g., in deflated form retained within or upon the end of a rigid or semi-rigid rod. Once positioned within the disc, either centrally within the annular shell or along the annular rim, a suitable gas (e.g., nitrogen or carbon dioxide) or the flowable load-bearing material can be delivered through the rod in order to inflate the balloon in situ, in a substantially radial or longitudinal direction. In some embodiments, beads of the load bearing strut material are simply packed into the balloon. The fact that the balloon is properly placed can be confirmed by the use of ancillary means, such as using a C-arm, or by self-effecting means embodied within the balloon itself or its delivery apparatus. In terms of its component parts, in one preferred balloon delivery system of the present invention there is provided an inflatable device, a motor drive unit, with a remote controller, associated tube sets, a nonscope inflow delivery cannula having independent fluid dynamics pressure and flow rate adjustments, attachments for the flush, vacuum, waste canister, and overflow jars. [0106]
  • Suitable materials for preparing balloons of the present invention may include those that are presently used for such purposes as balloon angioplasty. Suitable materials provide an optimal combination of such properties as compliance, biostability and biocompatability, and mechanical characteristics such as elasticity and strength. Balloons can be provided in any suitable form, including those having a plurality of layers and those having a plurality of compartments when expanded. A useful balloon apparatus will include the balloon itself, together with a delivery catheter (optionally having a plurality of lumen extending longitudinally therewith), and fluid or gas pressure means. [0107]
  • Examples of suitable materials (e.g., resins) for making balloons include, but are not limited to, polyolefin copolymers, polyethylene, polycarbonate, polyethylene terephthalate and ether-ketone polymers such as poly(etheretherketone). Such polymeric materials can be used in either unsupported form, or in supported form, e.g., by the integration of Dacron™ or other fibers. Preferably, the materials of construction of the balloon are resistant to softening or melting at a temperature of at least 80° C., preferably at least 100° C., more preferably at least 250° C. In addition, the balloon (or balloon-like structure) may be made out of any of a wide variety of woven or nonwoven fibers, fabrics, metal mesh such as woven or braided wires, and carbon. Biocompatible fabrics or sheet material such as ePTFE and Dacron™ may also be used. [0108]
  • Balloons can also take several forms, depending on the manner in which the biomaterial is to be delivered and cured. A single, thin walled balloon can be used, for instance, to contact and form a barrier along the interior surface of the remaining annular material. Once positioned, the flowable load bearing component can be delivered and solidified within the balloon to serve as a load bearing strut of the present invention. In such an embodiment, the balloon is preferably of a type that will allow it to remain in position, without undue detrimental effect, between the annular material and the solidified load-bearing component. [0109]
  • Optionally, a balloon can be provided that fills essentially only the central portion of the disc space. In such an embodiment, the balloon can be, for instance, in the shape of a cylinder. Such a balloon can be provided such that its upper and lower walls can be positioned to contact the opposing vertebral bodies, and its side walls will provide sufficient strength to cause, distraction of the space upon inflation. Thereafter, the load-bearing component is delivered to the perimeter of the annular space, i.e., the space between the annular material and the balloon, and there solidified. Optionally, the balloon can be gradually deflated as additional biomaterial is inserted into the space. Then, once the load bearing material is stably positioned, the osteobiologic component is introduced into the balloon, thereby filling the balloon. [0110]
  • In some embodiments, the balloon has metallic wires or other imageable means incorporated into it. Any material that can be seen under fluoroscopy would be acceptable. Potential materials include any metal, metal alloys, or ceramics that could be combined with a polymer. The material can be in the form of wires, a mesh, or particles incorporated into the balloon or on its surface. [0111]
  • In some embodiments, the balloon has an inner surface that is chemically active so as to bond with the balloon filler as it polymerizes. As used herein, a chemical “bond” is said to exist between two atoms or groups of atoms when the forces acting between them are strong enough to lead to the formation of an aggregate with sufficient stability to be regarded as an independent species. As used herein, “chemically active” means capable of forming a chemical bond. In one example, the surface is chemically modified by means such as plasma polymerization. In this case, the balloon is placed in a vacuum chamber and plasma containing a small molecule (an amine for example) is created. The balloon surface is bombarded by the small molecule and the small molecule is chemically attached to its surface. The balloon's surface with its amine groups can then react with the polymer that is injected into the balloon (i.e., an epoxy), forming a device that would have greater fatigue properties since the “composite” of balloon and balloon filler are chemically bonded to one another. [0112]
  • The desired quantities of the load-bearing and osteobiologic components of the present invention are delivered by minimally invasive means to the prepared site. Prior to delivery, these components can be stored in suitable storage containers, e.g., sterile, teflon-lined metal canisters. The flowable components can be delivered, as with a pump, from a storage canister to the delivery cannula on demand. The components can be delivered in the form of a single composition, or can be delivered in the form of a plurality of components or ingredients. [0113]
  • In some embodiments, the inflatable device can be filled with a viscous material that later solidifies to form the strut or osteobiologic component. The viscous material can be a heated polymer (such as a composition containing polycaprolactone), or polymer precursor components (such as the photopolymerizable anhydrides disclosed by A. K. Burkoth, [0114] Biomaterials (2000) 21:2395-2404, the entire teachings of which are incorporated herein by reference).
  • In some embodiments, a flowable load bearing composition, such as polycaprolactone, heated to a temperature yielding a viscosity in the range of from about 100 to about 500 cps is injected into the balloon under pressure such as by using a pump and pressure within the range of from about 4 ATM to about 10 ATM or more depending upon viscosity, balloon strength and other design considerations. The pump is run for a sufficient duration and under a sufficient pressure to ensure that the polycaprolactone wets all of the p-dioxanone fibers. This may range from about 10 minutes or more to about an hour, and, in one application where the pump was run at about 5 ATM pressure, requires at least about 1 hour. Specific method parameters may be optimized depending upon the viscosity of the polycaprolactone, infusion pressure, infusion flow rate, density of the packed fibers, and other variables as will be apparent to those of skill in the art in view of the disclosure herein. [0115]
  • It has been reported in the literature that balloons inserted into the disc space may be subject to retropulsion. Therefore, in some embodiments of the present invention, upon expansion, the inflatable device forms an upper surface having a first plurality of teeth projecting outwards from the upper surface. Upon expansion of the device, these teeth will project in the direction of the upper endplate and, upon complete expansion of the device, will engage the endplate to from a secure interlock with the endplate and resist retropulsion. [0116]
  • Preferably, the teeth are made of a stiff resorbable material, such as polyetheretherketone (PEEK). Preferably, the teeth have a height of between 0.5 and 1.5 mm, and have a triangular cross-section. [0117]
  • In some embodiments of the present invention, upon expansion, the inflatable device forms an upper surface formed of a material having a high coefficient of friction. Upon expansion of the device, the high coefficient of friction of the upper and lower surfaces will case a drag upon any movement of the upper surface and therefore keep the device in place and resist retropulsion. [0118]
  • Preferably, the upper and lower surfaces of the inflatable device are made from a material selected from a group consisting of polyether block copolymer (PEBAX), ABS (acrylonitrile butadiene styrene); ANS (acrylonitrile styrene); Delrin®; PVC (polyvinyl chloride); PEN (polyethylene napthalate); PBT (polybutylene terephthalate); polycarbonate; PEI (polyetherimide); PES (polyether sulfone); PET (polyethylene terephthalate); PETG (polyethylene terephthalate glycol), high and medium melt temperature: polyamides, aromatic polyamides, polyethers, polyesters, Hytrell®, polymethylmethacrylate, polyurethanes: copolymers, EVA (ethylene vinyl acetate) or ethylene vinyl alcohol; low, linear low, medium and high density polyethylenes, latex rubbers, FEP, TFE, PFA, polypropylenes, polyolefins; polysiloxanes, liquid crystal polymers, inomers, Surlins, silicone rubbers, SAN (styrene acrylonitrile), nylons: 6, 6/6, 6/66, 6/9, 6/10, 6/12, 11, all [0119] PEBAXs 12; polyether block amides; thermoplastic elastomers and the like.
  • In some embodiments, the vertebral endplates opposing the disc space are roughened. The roughening provides hills and valleys into which a flowable polymer can flow and harden, thereby forming a mechanical interlock between the device and the bony surface and resisting retropulsion. [0120]
  • The roughening can be provided mechanically (as with a curette), or chemically (as by an acid), or by an energy-transmitting device (as with an ablation unit preferably assisted with hyperconductive fluid, such as hypertonic saline). [0121]
  • In some embodiments, the flowable polymer forming a mechanical interlock can be a separate layer. In others, the flowable polymer can be a component of the strut. In others, the flowable polymer can be a component of the osteobiologic composition. [0122]
  • In some embodiments, the strut portion of the device can have an outer layer of a scaffold material appropriately seeded with osteogenic factors and/or growth factors to produce quick bone ingrowth, thereby effectively locking the strut in place. [0123]
  • In some embodiments, an outer layer of a scaffold material appropriately seeded with osteogenic factors and/or growth factors can also be applied to a balloon component of the osteobiologic component. The seeding again produces quick bone ingrowth, thereby effectively locking the osteobiologic component in place. [0124]
  • Balloons of the present invention can be made using materials and manufacturing techniques used for balloon angioplasty devices. U.S. Pat. No. 5,807,327 by Green, the entire teachings of which are incorporated herein by reference, (hereinafter “Green”) discloses balloons that may be used in the present invention. The materials disclosed by Green for the formation of the balloon include tough non-compliant layer materials (col. 8, lines 18-36) and high coefficient of friction layer materials (col. 8, lines 42-54). [0125]
  • Now referring to FIGS. [0126] 5(a) and (b), in some embodiments, the load-bearing component is delivered into the disc space through an inflatable balloon 12, and the osteobiologic component 20 is freely injected. This embodiment is desirable because the balloon 12 can act as a barrier to hydrolysis of the load-bearing component, thereby increasing the longevity of the load-bearing component. In contrast, the absence of the balloon covering the osteobiologic component may be desirable in instances in which it is desirable to immediately begin the bone growth process.
  • This embodiment may also be desirable in instances in which the load-bearing component comprises a cross-linkable composition, and the surgeon desires to provide a barrier between the patient's tissue and the precursors during the reaction of the precursors. [0127]
  • Now referring to FIGS. [0128] 6(a) and (b), in some embodiments, both the load bearing and the osteobiologic components are delivered into the disc space using a device comprising two separate inflatable balloons 12. This embodiment is desirable in instances in which both the annulus fibrosis has been functionally breached, and there is a concern that flowable materials would flow from the disc space and through the breach and into the remainder of the body. In this embodiment, it is preferred that the balloon containing the osteobiologic material be at least semi-permeable to nutrients and preferably resorbable. As used herein, the term “semipermeable” refers to a material that is non-permeable to the flowable materials described above yet permeable to important water and nutrients to support bone growth therein. Suitable semi-permeable materials include both porous and non-porous polymeric constructs such as films, fabrics (woven and non-woven) and foams.
  • In some embodiments, both the load bearing and the osteobiologic components are delivered into the disc space through the same inflatable device. [0129]
  • Now referring to FIGS. [0130] 7(a) and (b), another embodiment of the device and method of the present inevtion is shown wherein the device comprises at least two inflatable balloons 12. In this embodiment, the load-bearing component is delivered into the disc space through at least two inflatable balloons 12 and the osteobiologic component 20 is freely injected into the disk space using the space between the ballons.
  • In some embodiments, the osteobiologic component is delivered into the disc space through an inflatable device, and the load-bearing component is freely injected. This embodiment may be desirable in instances in which the osteobiologic component comprises an in situ hardenable composition such as a calcium containing cement, or a crosslinkable polymer such as poly(propylene fumarate), polyanhydride, or polyoxaester, and the surgeon desires to cordon off the patient from the precursors during their reaction. In this embodiment, it is further preferred that the balloon containing the osteobiologic material be at least semi-permeable to nutrients and preferably resorbable. This embodiment may also be desirable in instances in which the load-bearing composition comprises growth factors and the surgeon desires to immediately begin the bone growth process in the load-bearing component. [0131]
  • In some embodiments, the load-bearing component is delivered into the disc space through an inflatable device, and the osteobiologic component is freely injected. This embodiment may also be desirable in instances in which the annulus fibrosis in essentially intact and the surgeon desires to immediately begin the bone growth process in the load-bearing component. [0132]
  • In some embodiments, the inflatable device comprises a single peripheral wall having an upper and lower surface, upper and lower walls, and a cavity formed therebetween. For the purposes of the present invention, this shape of this embodiment is referred to as a “puck”. The peripheral wall and upper and lower walls of the puck could be designed so as to be percutaneously deliverable through a cannula having an inside diameter of between 0.5 and 18 mm, preferably no more than 4 mm. [0133]
  • In one embodiment, the peripheral wall of the puck is designed to be load bearing when the inflatable device is disposed in its inflated position. Preferably, the peripheral wall is made of a shape-memory metal, such as Nitinol, or a thin film alloy. [0134]
  • In some embodiments, the periphery of the balloon is reinforced with fibers. In some embodiments thereof, the peripheral wall comprises polymer fibers. These fibers can be made into a weave that is sufficiently flexible (in the longitudinal direction of the fiber) to pass through the cannula and expand into the expanded state. Typically, these fibers have high tensile strengths so that they can very efficiently accommodate the problematic hoop stresses that may be transferred from the osteobiologic component contained within the middle annulus of the balloon. [0135]
  • Various patterns of reinforcement of the periopheral side-walls with the fibers are contemplated. In one embodiment, the fibers form X-shaped cross-hatching pattern. In another embodiment, the fibers form a continuous wave-like pattern having peaks and troughs, where said peaks and troughs approach upper and lower surfaces. [0136]
  • In one embodiment, the walls of the device are reinforced by an internal frame forming a polygonal structure having sides on the upper, lower and peripheral surfaces. [0137]
  • In some embodiments, the peripheral reinforcement is made of a resorbable polymer fiber. [0138]
  • The upper and lower walls of this puck embodiment are designed to initially accept and contain the osteobiologic component that is flowed into the puck cavity. Accordingly, the upper and lower walls should be at least semi-permeable so as to contain the osteobiologic component. In preferred embodiments, the upper and lower walls are made of a resorbable material that quickly resorbs, thereby exposing the contained osteobiologic material to blood flowing from the decorticated endplates. [0139]
  • In some embodiments, this absorbable material has an elastomeric quality. This elastomeric quality allows the resorbable upper and lower walls to be delivered through the cannula, and flatten upon device expansion. In preferred embodiments, this elastomeric polymer is selected from the materials disclosed in U.S. Pat. No. 6,113,624 by Bezwada, the entire teachings of which are incorporated herein by reference (hereinafter “Bezwada”). In other embodiments, this absorbable material is not elastomeric, and is preferably made of a thin film metal alloy or a braided metal alloy. [0140]
  • Now referring to FIGS. [0141] 8(a) and 8(b) there is provided a device 30 of the present invention comprising an inflatable portion 32 that includes an arcuate inflatable balloon.
  • Now referring to FIG. 8([0142] a), in its pre-deployed state, the inflatable portion 32 of the device 30 is conveniently repeatedly folded upon itself, thereby decreasing the size of the device 30 and allowing for minimally invasive insertion into the disc space. During insertion into the disc space, the device 30 is preferably inserted in the sandwich orientation as shown in FIG. 8(a) wherein the structural walls 34 are disposed essentially parallel to the vertebral endplates. The sandwich orientation allows height H of the structural walls 34 to meet or exceed the disc space height, while the folded width W does not exceed the disc space height.
  • Now referring to FIG. 8([0143] b), after insertion into the disc space, fluid is flown into the inflatable portion 32 of the device 30, thereby expanding the device 30 into the configuration as shown. The height H of the structural walls 34 is sufficient to restore the natural height of the disc space. After the device 30 distracts the disc space, the cavity, formed by the expanded portion 32, is filled by an osteobiologic component.
  • The [0144] structural walls 34 of this embodiment are preferably attached to the inflatable portion 32 by an adhesive. The structural walls 34 should be designed so that the width W and the strength and modulus of the material of construction allow for both support of the disc space and bony fusion through the osteobiologic component.
  • In some embodiments, the height H of the [0145] structural wall 34 is at least equal to the height of the natural disc space. This condition desirably restores the height of the disc space when the inflatable portion 32 is expanded. In some embodiments, the height H of the anterior portion of the wall 34 is greater than the height h of the posterior portion of the wall 34. This condition desirably provides a lordotic effect upon expansion of the inflatable portion 32.
  • In some embodiments, the [0146] walls 34 are made of allograft bone, and preferably comprise cortical bone. In others, the walls are made of a synthetic resorbable polymeric material. In some embodiments, the walls may be sufficiently porous to provide an effective scaffold, thereby allowing bony fusion therethrough.
  • In some embodiments, the [0147] wall component 34 of this embodiment is made of bone graft. In alternative embodiments, component 34 comprises additional inflatable portions. After insertion into the disc space, a load bearing composition may be flowed into the cavities of these additional inflatable portions, thereby expanding these additional inflatable portions and eventually producing the desired dimensions of the walls 34.
  • In some embodiments, each [0148] wall 34 is translaterally oriented in the expanded device. In this condition, a first wall supports essentially the anterior portion of the opposing cortical rims, while the second wall supports essentially the posterior portion of the opposing cortical rims, so that one of these walls will essentially bear the entire load during flexion and the other wall will bear essentially the entire load during extension. Preferably, these walls have a length L corresponding to the anterior and posterior aspects of the cortical rim.
  • The [0149] inflatable portion 32 has upper and lower surfaces 36 and 38 for contacting the adjacent vertebral endplates, a peripheral side surface 40 connecting the upper and lower surfaces 36 and 38, and an opening 42 in the peripheral side surface 40. Upon a flow of fluid through the opening 42 from a cannula 18, the inflatable portion 32 is expanded and surfaces 36, 38 and 40 are pushed apart sufficiently to form an internal cavity suitable for containing an osteobiologic component. Because the osteobiologic component retained within this cavity is preferably at least semipermeable in order to provide bony fusion, the upper and lower surfaces 36 and 38 of the inflatable portion 32 preferably do not act as barriers to bony fusion. Accordingly, it is preferred that the upper and lower surfaces 36 and 38 are either porous (preferably, semipermeable) or quickly resorbable. Preferably, the upper and lower surfaces 36 and 38 are made of a material that resorbs within 7 days, preferably 3 days, preferably one day. Examples of fast-resorbing materials include denatured collagen, polysaccharide-based materials such as starch and oxidized regenerated cellulose, and hydroxylated lactide-glycolide copolymers. In some embodiments, the opening in the side surface 40 is formed closely adjacent to the structural wall 34, positioned anteriorly on a vertebral endplate.
  • In some embodiments, the [0150] inflatable device 30 of this embodiment has a configuration designed to match the geometry of the disc space, and is selected from the group consisting of an anterior lumbar interbody fusion (ALIF) configuration, a posterior lumbar interbody fusion (PLIF) configuration, a vertebral body replacement (VBR) configuration, and an anterior cervical discectomy and fusion (ACDF) configuration.
  • By reducing the effective size of the [0151] device 30, this embodiment of the present invention desirably minimizes the access window required for insertion of intervertebral devices. By providing anatomically appropriate structural walls 34, the device 30 provides a stable environment for the muskuloskeletal growth factors to develop.
  • Now referring to FIGS. [0152] 9(a) and (b), one embodiment of an inflatable device of the present invention is shown. The device 60 comprises an outer side-wall component 62, an inner side-wall component 64, and a balloon 66 disposed between and attached to said inner and outer wall components. The short cranial-caudal height of the inner and outer walls allows for the device to be inserted into the disc space without having to distract the disc space prior to insertion. Subsequent filling of the balloon with an in-situ hardenable, load-bearing material causes the balloon to expand beyond the cranial and caudal margins of the sidewalls, thus providing the necessary distraction of the disc space. Furthermore, the sidewalls prevent expansion of the balloon such that the thickness of the device is minimized upon inflation. Minimized wall thickness is important for ensuring maximum area for bone growth (fusion) between the adjacent vertebrae. In some embodiments, the footprints of the outer and inner side- wall components 62 and 64 represent substantially equal arcs of two concentric circumferences. This allows placing device 60 along the periphery of the anterior portion 14 of a vertebral endplate 8 and filling a cavity therewithin with a load bearing material.
  • In some embodiments of [0153] device 60, the outer and inner walls 62 and 64 are made of a flexible plastic such as poly(ethyleneterephthalate), a superelastic metal such as Nitinol, or a flexible material/geometry combination, whereby each wall can be deformed into a relatively elongated shape for delivery to the disc space through a cannula 18. The sidewalls are sufficiently rigid to guide the device into the desired location in the disc space but sufficiently flexible to allow delivery through the cannula. Referring to FIG. 9(c), during the insertion of the device 60, upon release from the cannula 18, components 62 and 64 can then take on the desired arcuate shape. Referring to FIG. 9(d), subsequent to insertion, the device 60 is expanded by injecting a load-bearing component, an osteobiologic component or a combination thereof into a cavity formed by the components 62, 64, and 66. Any suitable injection means can be used, for example, a syringe pump 70.
  • The above characteristics of [0154] components 62 and 64 ensure that the cavity produced between side walls 62, 64 can be filled so that the device 60 distracts the disc space and can also create a wedge shape for creating or restoring healthy curvature of the spine.
  • An alternative embodiment of inflatable device of the present invention is shown in FIGS. [0155] 10(a) and (b). Device 260 comprises an upper wall component 266 and a lower wall component 268 joined by an inflatable balloon 270. In some embodiments, the footprints of the upper and lower wall components 266 and 268 represent substantially equal arcs of two concentric circumferences. This allows placing device 260 along the periphery of the anterior portion 14 of a vertebral endplate 8 and filling a cavity therewithin with a load bearing material.
  • In some embodiments of [0156] device 260, the upper and lower wall components 266 and 268 are made of a superelastic material such as Nitinol, or a flexible material/geometry combination, whereby each wall can be deformed into a relatively elongated shape for delivery to the disc space through a cannula 18. Operationally, device 260 is similar to device 60. Insertion of device 260 can be accomplished in a manner depicted in FIG. 9(c). Upon release from cannula 18, components 266 and 268 can then take on the desired arcuate shape. Subsequent to insertion, device 260 is inflated by injecting a load-bearing component, an osteobiologic component or a combination thereof into balloon 270. Any suitable injection means can be used, for example a syringe pump.
  • Preferably, [0157] balloon 270 is semi-permeable. In preferred embodiments, balloon 270 is made of a material that quickly resorbs, thereby exposing the contained osteobiologic material to blood flowing from the decorticated endplates.
  • Generally, the strut is deliverable through a cannula having an inside diameter of between 3 mm and 18 mm, preferably between 4 mm and 12 mm, more preferably between 5 mm and 10 mm. [0158]
  • In some embodiments in which the surgeon desires to minimize the size of the incision, the strut is preferably deliverable through a cannula having an inside diameter of between 0.5 mm and 6 mm, preferably between 1 mm and 4 mm, more preferably between 2 mm and 3 mm. [0159]
  • Preferably, the upper and lower surfaces of the upper and lower walls, respectively, have teeth that prevent excessive movement of the strut after implantation. [0160]
  • Now referring to FIGS. [0161] 11(a) and (b), the device 80 comprises four rail components 82 wherein the footprints of the rail components 82 represent substantially equal arcs of two concentric circumferences. Components 82 are joined by an inflatable balloon 84 such that the device can be inserted in a collapsed configuration as shown in FIG. 11(b) and then expanded as shown in FIG. 11(a) once filled with a load-bearing material to increase disc height and provide thickness for load bearing support.
  • In one embodiment of the present invention, [0162] device 80 is shown in FIGS. 12(a) and (b). In this embodiment, device 80 is delivered in a generally diamond-shaped configuration, shown in plan view on FIG. 12(a) and in lateral view in FIG. 12(b). In this embodiment, the upper and lower rails 82 will cause slight subsidence of the vertebral body endplates, thus providing stability of the implanted device.
  • Now referring to FIGS. [0163] 13(a) through (d) a preferred embodiment of the method of the present invention is shown. As shown in FIG. 13(a) and 13(b), a cannula 18 is inserted into an intervertebral space. Next an inflatable balloon 12 of a generally toroidal shape is inserted through the cannula 18 into the intervertebral space. The balloon 12 is expanded by directing a load-bearing component into said balloon. Referring to FIG. 13(c), subsequent to balloon expansion, osteobiologic component 20 is injected into the open cavity defined by the outer surface of the balloon 12. Preferably, the osteobiologic component comprises a water-soluble component. Next, the water-soluble component is dissolved, thus forming a porous matrix shown in FIG. 13(d).
  • In one embodiment of the present invention the load-bearing component is delivered through a balloon, and the osteogenic component is provided in a hydrogel phase of the osteobiologic component. Examples of suitable hydrogels are provided hereinbelow. [0164]
  • In other embodiments, solid components of the strut are inserted into the body percutaneously and assembled in situ to form the strut. In some in situ embodiments, the strut is formed by bonding together two bondable components. Preferably, the bondable materials are selected from the group consisting of heat bondable materials such as polycaprolactone, and polymerizable materials such as poly(propylene fumarate) and polyoxaesters including photo-curable materials such as polyanhydrides. [0165]
  • In other embodiments, load-bearing materials in the form of beads is delivered into the inflatable device and packed into the device so as to create a stable strut having an open interstitial porosity. In some embodiments, the beads may be packed without subsequent stabilization other than closing off the opening of the balloon. In these embodiments, the beads are preferably polyarylether ketone (PAEK), more preferably polyetherether ketone (PEEK) with chopped carbon fiber. [0166]
  • In some embodiments, a bonding material may be subsequently flowed into the interstitial porosity to further stabilize the packed beads. Preferably, this bonding material comprises an aliphatic polyester such as polycaprolactone (PCL). The bonding material may be resorbable and may include osteogenic additives such as growth factors and stem cells. [0167]
  • In some bead embodiments of the device, the beads of the load-bearing material are made of a heat-bondable material, such as polycaprolactone. When the beads are so constituted, heat may be delivered into the packing and soften the contacting surfaces of the beads. Upon subsequent cool down to body temperature, the contacting surfaces solidify to further stabilize the packed structure. In some embodiments, the heat is provided exogenously. In other embodiments, the heat is provided by the patient's body heat (˜37° C.). [0168]
  • Now referring to FIGS. [0169] 14(a)-(d), another embodiment of the device of the present invention 300 comprises at least two bondable components 310 and 320, that are delivered into the disc space in unassembled form, placed closely adjacent one another, and then bonded together, preferably by heat bonding.
  • Referring to FIG. 14([0170] b), representing a lateral view of the device of FIG. 14(a) as seen in the direction of arrow A, and to FIG. 14(d), representing a perspective view of device 300, in one embodiment, device 300 comprises first and second portions 310 and 320. First portion 310 has a lower bearing wall 312, upper angled wall 314, and a leading wall 316 and a trailing wall 318. Second portion 320 has an upper bearing wall 322, lower angled wall 324 and a leading wall 326 and a trailing wall 328. The combined height of the assembled portion H exceeds that of the disc space. The angled walls form the same angle so that the leading edge of the second portion can be ramped up the angled wall of the first portion.
  • In use, the [0171] first portion 310 is placed in the disc space. Because the height of the first portion is less than the disc space, the first portion 310 is easily positionable anywhere within the disc space. Next, the second portion 320 is introduced into the disc space and ramped up the angled wall of the first portion. Corresponding rails and groove are provided on the angled walls of the first and second portion so as to guide the second portion along the an long wall of the first portion (see below). Because the second portion only contacts the lower portions of the first portion, the upper wall 322 of the second portion 320 does not touch the adjacent endplate during ramping and so the ramping is easy. Only when the ramping is essentially complete does the upper wall of the second portion contact the adjacent upper endplate. Preferably, the overall height of the ramp H is slightly greater than that of the disc space, so that distraction is achieved when the leading edge of the second portion reaches the leading edge of the first portion.
  • Referring to FIG. 14([0172] c), in one embodiment, a cross-section of the device of FIG. 14(a) is shown, taken along arrows B. As shown in FIG. 14(c), angled wall 314 of first portion 310 includes a grove 330, while angled wall 324 of second portion 320 includes a ridge 332, designed to fit into a slide against grove 330. In some embodiments, ridge 332 further includes a metal filament 334.
  • It is understood that the locations of [0173] grove 330 and ridge 332 can be interchanged to between angled walls 314 and 324 of upper and lower portions 310 and 320.
  • Preferably, the rail and groove feature of the ramps has a Morse taper so as to lock the ramp in its assembled form when the leading edge of the second portion reaches the leading edge of the first portion. [0174]
  • Once the two ramp portions are in place, an electric current or heat is passed through wire that passes through the length of the rail of the first portion. The resulting localized heating of the contacting areas softens this region without changing the dimensions of the ramp. Upon cooling, a highly stable, heat bonded ramp results. [0175]
  • Because the ramp of this embodiment is not flowed into the disc space, and the heating is very localized, extremely strong, high temperature materials such as PEEK may be used as the material of construction. In some embodiments, the ramp is made of a high temperature resorbable material. In some embodiments, the high temperature absorbable material is amorphous and has a glass transition temperature of above 100° C. Preferably, the amorphous absorbable is PLA. In some embodiments, the high temperature absorbable material is crystalline and has a melting point of above 100° C. Preferably, the crystalline absorbable is p-dioxanone. [0176]
  • In some ramp embodiments, a guidewire is guided through the center of the ramp guide. The guidewire would allow the ramps to be inserted over the guidewire. The guidewire could be remotely steered into place via IGS or equivalent, and then the ramps could be passed over the guidewire into place. The ramps could be semi-rigid which would allow them to follow the guidewire through the soft tissue, over the wire. [0177]
  • In other ramp embodiments, an “I”-Beam ramp cage is provided. The ramp cage discussed above could incorporate or mate with modular tops and bottoms. These tops and bottoms would have tracks, which would locate on guides fixed to the ramps (or the guides could be on the modular top, and tracks on the ramps) which would aid insertion and ensure the ramps were connected to these modular tops and bottoms. The surfaces of the modular tops and bottoms would go between the ramps and the vertebral bodies such that when assembled, a cross-section of the ramp/top/bottom assembly would resemble an “I”-Beam. This would allow for thinner ramps to ease insertion via an MIS technique or equivalent, and the modular tops and bottoms would provide sufficient surface area to prevent subsidence of the implant into the vertebral bodies. The ramps and modular tops could be shaped in several configurations, inserted assembled, or assembled within the disk space. [0178]
  • In other embodiments, there is provided a ribbon-shaped ramp having a longitudinal through-hole. A threaded rod is inserted through the middle of the ribbon so that, as the threaded rod is turned, the ribbon would “accordion” itself, increasing its height within the disk space. This “accordion”-ing could be achieved by other methods, such as a spring, a cable, etc. [0179]
  • Now referring to FIG. 15, one embodiment of a method of use of [0180] device 300 shown in FIGS. 14(a)-(d) is depicted. In this embodiment, the first and second ramp portions 310 and 320 are introduced translaterally so as to form a single ramp stretching essentially transversely across the disc space. This design in advantageous when used in a posterolateral approach, as this approach takes advantage of the fact that the muscle planes in the vicinity of the approach allow the implant to be delivered in a less invasive manner. In some embodiments thereof, the medial portion of the ramp has a height that is higher than the lateral portions. This feature provides the doming that is advantageous in interbody fusions
  • Now referring to FIG. 16, another embodiment of a method of use of [0181] device 300, shown in FIGS. 14(a)-(c) is depicted. In this embodiment, the ramp of the present invention may be advantageously used in a PLIF procedure. In particular, two ramps may be constructed in-situ so as to form bilateral struts similar to the Steffee struts.
  • Therefore, in accordance with the present invention, there is provided an intervertebral fusion device comprising a strut comprising: [0182]
  • a) a first component comprising: [0183]
  • i) a lower bearing surface adapted for bearing against a lower vertebral endplate, and, [0184]
  • ii) an upper surface comprising a leading end, an angled middle portion and a trailing end; and [0185]
  • b) a second component comprising: [0186]
  • i) an upper bearing surface adapted for bearing against an upper vertebral endplate, and, [0187]
  • ii) an upper surface comprising a leading end, an angled middle portion and a trailing end, [0188]
  • wherein the angled portion of the first component mates with the angled portion of the second component. [0189]  
  • In some embodiments of the present invention, the struts are completely dense. This feature maximizes the strength of the strut, and so is desirable for the load bearing. In other embodiments, the strut has openings sized to permit bony fusion therethrough. In some embodiments, the upper and lower walls have openings designed to promote bony fusion from the upper endplate to the lower endplate. In other embodiments, the sidewalls of the strut also have such openings. In some embodiments, the openings have a diameter of at least 2 mm. In other embodiments, the openings are in the range of from 50-500 um, more preferably between 100 and 300 um, preferably between 100 and 250 um. These preferred opening sizes are believed to be more conductive to bone growth. [0190]
  • Materials and Compositions Suitable for Use in the Invention [0191]
  • Provided below is a listing of various attributes of the load bearing composition and osteobiologic component of the present invention: [0192]
    Typical Load Typical
    Load Bearing Bearing Osteobiologic Osteobiologic
    Feature Application Application Application Application
    Resorption of >12 months, 12-24 months 1-3 months 2 months
    Matrix preferably
    beginning > 12
    months
    Overall High >50 MPa Moderate 1-5 MPa
    Strength
    Overall Cortico- 0.1-2 GPa Cancellous Bone 0.1-0.5 GPa
    Compression cancellous
    Modulus Bone
    Second Phase Reinforcement fibers Osteoconductive Nano HA
    particles
    Aqueous phase No no Yes Alginate
    Osteogenic No no Yes MSCs
    component
    Growth factors Yes BMP Yes BMP
    Footprint Support of disc 5-40 areal % Bony fusion volume 60-95 areal %
    space
  • As used herein, the term “second phase” refers to an additive that enhances the performance of the material, for example carbon fibers enhance the strength of the material and calcium phosphate particulates enhance the osteoconductivity of the material. As used herein, the term “aqueous phase” refers to a component of the material capable of maintaining cell viability, e.g. an alginate hydrogel. [0193]
  • Examples of load-bearing components that satisfy the above Table include at least one compound selected from the group consisting of poly(lactic acid), poly(glycolic acid), p-dioxanone fibers, polyarylethyl, polymethylmethacrylate, polyurethane, amino-acid-derived polycarbonate, polycaprolactone, aliphatic polyesters, calcium phosphate, unsaturated linear polyesters, vinyl pyrrolidone and polypropylene fumarate diacrylate or mixtures thereof. [0194]
  • Examples of osteobiologic components that satisfy the above Table include at least one member selected from the group consisting of mesenchymal stem cells, a growth factor, cancellous bone chips, hydroxyapatite, tri-calcium phosphate, polylactic acid, polyglycolic acid, polygalactic acid, polycaprolactone, polyethylene oxide, polypropylene oxide, polysulfone, polyethylene, polypropylene, hyaluronic acid, bioglass, gelatin, collagen and a polymeric fiber. [0195]
  • Because the overall mechanical properties of the load bearing and osteobiologic components can be significantly varied by the inclusion or exclusion of additives such as fibers, particles, cross-linking agents and aqueous phases, some matrix components may be used in some instances as the matrix for the load bearing component and in other instances as the matrix for the osteobiologic component. For example, polycaprolactone may be used in conjunction with p-dioxanone reinforcing fibers as a matrix for a load bearing component, and may also be used in conjunction with polylactic acid and hydroxyapatite as a matrix for an osteobiologic component. [0196]
  • For the purposes of the present invention, the term “hardenable” refers to a material that can be delivered through a cannula into the disc space in a viscous form. In one embodiment, material that can be delivered through a cannula, having at least about 6 mm internal diameter. In another embodiment, a cannula has a diameter of no more than about 6 mm. [0197]
  • Generally, the flowable load-bearing composition and osteobiologic component of the present invention are flowable, meaning they are of sufficient viscosity to allow their delivery through a cannula of on the order of about 2 mm to about 6 mm inner diameter, and preferably of about 3 mm to about 5 mm inner diameter. Such biomaterials are also hardenable, meaning that they can solidify, in situ, at the tissue site, in order to retain a desired position and configuration. [0198]
  • In some instances, the hardenable material is simply a material (such as a low temperature polymer) having a melting point (for crystalline materials) or a glass transition temperature (for amorphous materials) less than 100° C., and is solid a body temperature (37° C.). In some embodiments, these low temperature materials are simply heated to the point where they are viscous and flowable and then injected into the disc space. The subsequent cooling of the viscous material to body temperature then solidifies them. Because these materials do not need to react in-situ, they are desirable for their relative inertness. Accordingly, in some embodiments, they may be freely injected into the disc space without a protective balloon. [0199]
  • In some instances, the hardenable material comprises a cross-linkable component (or “cross-linking agent”). These materials are desirable because cross-linking enhances the strength of the resulting material. Accordingly, in some embodiments, the load-bearing component comprises a cross-linking agent. In such embodiments, it is desirable that the cross-linking agent be delivered into the disc space through a balloon so that the balloon may protect the surrounding tissue from the reactive components during the reaction. [0200]
  • In some embodiments, the load-bearing component comprises a cross-linking agent. In some embodiments, the osteobiologic component comprises a cross-linking agent. [0201]
  • In some embodiments, the hardenable material comprises a polymer and a cross-link agent. In some embodiments, the hardenable material may further comprise a monomer. In some embodiments, the hardenable material may further comprise an initiator. In some embodiments, the hardenable material may further comprise an accelerant. [0202]
  • Preferably, the cross-linking component is made from a two-part composition comprising a monomer and a crosslinking agent. [0203]
  • In some embodiments, the cross-linked composition is flowable at a temperature of between 37° C. and 40° C. [0204]
  • In preferred embodiments, the cross-linkable component is resorbable. For the purposes of the present invention, a resorbable material loses 50% of its initial strength within no more than two years after implantation. [0205]
  • Providing a resorbable cross-linkable component is desirable because it not only provides the high initial strength required for supporting the disc space in an intervertebral fusion application, but also allows for the eventual replacement by bone fusion. [0206]
  • In some preferred embodiments, the resorbable cross-linkable component comprises those cross-linkable components disclosed by Wise in U.S. Pat. No. 6,071,982, the entire teachings of which are incorporated herein by reference. [0207]
  • In preferred embodiments, the cross-linkable component is UV curable. Examples of UV curable cross-linkable components are disclosed in Biomaterials (2000), 21:2395-2404 and by Shastri in U.S. Pat. No. 5,837,752, the entire teachings of which are incorporated herein by reference. [0208]
  • In some embodiments, the cross-linkable component is water-curable. In such instances, the resulting body is typically somewhat weak, and so it is preferred that the water-curable cross-linkable compound be used as a matrix for the osteobiologic component. [0209]
  • In some embodiments, the strut is made of a non-resorbable material. Since the non-resorbable material does not degrade over time, the use of the non-resorbable material provides the surgeon with a measure of safety and prevents collapse of the disc space in the event the osetobiologic composition does not produce a fusion. [0210]
  • Preferably, the non-resorbable material is a polymer. The selection of a polymer allows the material to be flowed into place. [0211]
  • In some embodiments, the load bearing polymer is a polyarylethyl ketone (PAEK). More preferably, the PAEK is selected from the group consisting of polyetherether ketone PEEK, polyether ketone ketone PEKK and polyether ketone PEK. In preferred embodiments, the PAEK is polyetherether ketone. [0212]
  • In general, although they possess high strength, PAEK-type polymers have a very high melting point (e.g., 250° C.) and so are not amenable to flow at desirable temperatures. Accordingly, embodiments of the present invention using PAEK as the load bearing composition would typically deliver PAEK in a solid form, such as in bead form or as pre-constructed components, and then assemble and heat bond the components in the disc space under very high temperatures (e.g., 250° C.). These high temperatures would likely require the use of a highly insulated expanded device. [0213]
  • In some embodiments, the strut is a composite comprising fiber, preferably carbon fiber. Composite struts comprising carbon fiber are advantageous in that they typically have a strength and stiffness that is superior to neat polymer materials such as a polyarylethyl ketone PAEK. [0214]
  • In some embodiments, the fiber, preferably, carbon fiber, comprises between 1 percent by volume and 60 percent by volume (vol %). More preferably, the fiber comprises between 10 vol % and 50 vol % of the composite. In some embodiments, the polymer and carbon fibers are homogeneously mixed. In others, the composite strut is a laminate. In some embodiments, the carbon fiber is present as chopped state. Preferably, the chopped carbon fibers have a median length of between 1 mm and 12 mm, more preferably between 4.5 mm and 7.5 mm. In some embodiments, the carbon fiber is present as continuous strands. [0215]
  • In especially preferred embodiments, the composite strut comprises: [0216]
  • a) about 40% to about 99% (more preferably, about 60% to about 80 vol %) polyarylethyl ketone PAEK, and [0217]
  • b) about 1% to about 60% (more preferably, about 20 vol % to about 40 vol %) carbon fiber, [0218]
  • wherein the polyarylethyl ketone PAEK is selected from the group consisting of polyetherether ketone PEEK, polyether ketone ketone PEKK and polyether ketone PEK. [0219]
  • In some embodiments, the composite strut consists essentially of PAEK and carbon fiber. More preferably, the composite strut comprises about 60 wt % to about 80 wt % PAEK and about 20 wt % to about 40 wt % carbon fiber. Still more preferably the composite strut comprises about 65 wt % to about 75 wt % PAEK and about 25 wt % to about 35 wt % carbon fiber. [0220]
  • In the context of an arc-shaped inflatable container, for use as a container for the load bearing composition of the present invention, the physical requirements of the flowable load bearing component will depend upon the length and diameter of the arc as well as the physical requirements imposed by the implantation site. For certain embodiments, certain load-bearing compositions may or may not exhibit sufficient physical properties. Physical properties of the load bearing components can also be modified through the addition of any of a variety of reinforcements, such as carbon fibers, Kevlar™ or Titanium Rods, woven or laser etched metallic tubular stents, or other strength enhancers as will be understood in the art. [0221]
  • Certain composite materials, such as carbon fibers embedded in a bonding agent such as a polycaprolactone are believed to be particularly useful in forming the load bearing component of the present invention. For example, graphite (carbon fibers) having a diameter within the range of from about 0.003 to about 0.007 inches is provided in bundles (tows) composed of from about 3,000 to about 12,000 fibers. One typical fiber useful for this purpose is manufactured by Hexcel Carbon Fibers, Salt Lake City, Utah, Part No. HS/CP-5000/IM7-GP 12K. Preferably, the Tow tensile strength is in the range of from about 5,000 to about 7,000 Mpa. Tow tensile modulus is within the range of from about 250 to about 350 Gpa. Within the range of from about 30 to about 60 bundles of the carbon fiber described above is packed in a deflated balloon, optionally along with a Ni—Ti stent having an 8 mm diameter and 8 cm length. Although any of a variety of stents may be utilized, one useful structure is similar to the Smart Stent (Cordis), and it helps keep the structure intact and also adds structural strength to the implanted structure. [0222]
  • In an alternate embodiment, carbon fibers having within the range of from about 15 to about 45 degrees of braids are utilized within the inflatable device to reinforce the load bearing material. The braid may be in the form of a plain weave, and may be obtained, for example, from Composite Structures Technology (Tehachapi, Calif.). A 0.5 inch diameter of 45 degrees braided carbon fiber sleeve is positioned within the center of the balloon. This braided sleeve conforms dimensionally to the inside diameter of the balloon. A 0.3 inch diameter braided carbon sleeve may also be positioned concentrically within the balloon, within the outer braided carbon fiber sleeve. Unidirectional fibers are thereafter introduced inside of the ID of the inner braided carbon sleeve. Unidirectional fibers are also introduced into the annular gap between the two braided sleeves. The volume of the fiber per volume of balloon is generally within the range of from about 40% to about 55%. After placement of the foregoing structure within the portals of the screws, the flowable load bearing material of the present invention having a viscosity within the range of from about 100 cps to about 500 cps is injected under 10 atmospheres pressure into the balloon. The use of braided sleeves will produce higher structural resistance to sheer stress as a result of torsional loads, plus the ability to distribute unidirectional fibers in a homogenous manner within the balloon at all times. [0223]
  • In some embodiments, the polymer comprises polymethylmethacrylate (PMMA). In preferred embodiments, the matrix comprises a radio-opaque agent. A blend of diurethane dimethacrylate (DUDMA) and triethylene glycol dimethacrylate (TEGDMA) that is suitable for the load bearing strut is disclosed in WO 03/005937, the entire teachings of which are incorporated herein by reference. [0224]
  • In some embodiments, the load bearing composition comprises polyurethane. In some embodiments, the polyurethane materials disclosed in U.S. Pat. No. 6,306,177 by Felt (hereinafter “Felt”), the specification of which is incorporated by reference to the extent it is not inconsistent with the remainder of the specification, is selected. [0225]
  • Polyurethanes can be tailored to have optimal stiffness by adjusting the ratio of soft segment to hard segment ratio in the polymer. Furthermore, polyurethanes can be prepared as two-part systems that will cure upon mixing. Preferred polyurethanes, e.g., thermoplastic polyurethanes (“TPU”), are typically prepared using three reactants: an isocyanate, a long-chain macrodiol, and a short-chain diol extender. The isocyanate and long-chain diol form a “soft” segment, while the isocyanate and short-chain diol form a “hard” segment. The hard segments form ordered domains held together by hydrogen bonding. These domains act as cross-links to the linear chains, making the material similar to a cross-linked rubber. It is the interaction of soft and hard segments that determines and provides the polymer with rubber-like properties. [0226]
  • In some embodiments, the strut comprises a photocurable material. In some photocurable embodiments, the material comprises organophosphorous compounds. These compounds are advantageous because the resulting product is calcium phosphate based, and so is both biocompatible and resorbable. [0227]
  • In some embodiments the strut has a resorbable matrix material. A resorbable matrix material is desirable because it is eventually resorbed by the body, and may eventually be replaced by bone. [0228]
  • In some embodiments, the resorbable strut is a high temperature material. For the purposes of the present invention, a high temperature material flows above 100° C. In these cases, the high temperature absorbable material enters the disc space as a plurality of components in a solid form. The components are then contacted in the disc space, and heat is applied to bond the components without deforming the assembled shape. [0229]
  • In some embodiments, the load bearing composition includes a matrix comprising an amino-acid derived polycarbonate. [0230]
  • In some embodiments, the osteobiologic component comprises a matrix comprising a biodegradable polyurethane. [0231]
  • In some embodiments, the osteobiologic component comprises a matrix comprising an amorphous polymer and has a glass transition temperature of below 100° C. Preferably, the amorphous absorbable is D,L-polylactic acid (PLA). [0232]
  • In general, little modification of polylactic acid polymers is possible because there are no other functional groups on the side chain, except the methyl of the lactic acid residue. One possibility to modify the properties of these polymers is to form copolymers with residues having more diverse side chain structures, e.g., lysine. [0233]
  • A poly(lactide-co-lysine) functionalized with peptide containing the arginine-glycine-aspartate (RGD) sequence was prepared by removal of the benzyoxycarbonyl protecting group on the lysyl residue and peptide coupling. The peptide concentration was found to be approximately 3.1 mmol/g, which could be translated into a peptide surface density of 310 fmol/cm[0234] 2. A surface density of as low as 1 fmol/cm2 of an RGD peptide has been previously determined to promote cell adhesion to an otherwise nonadherent surface (Massia and Hubbell, 1991). Therefore, by carefully processing the copolymer, biodegradable films with cell adhering properties can be prepared from the copolymer of lactide and lysine.
  • Other strategies have also been employed to widen the properties of polylactides. For example, polylactic acid (PLA) has also been synthesized as an acrylic macromonomer and subsequently copolymerized with polar acrylic monomers (e.g., 2-hydroxyethylmethacrylate) (Barakat et al., 1996). These polymers were studied as amphiphilic graft copolymers for drug delivery purposes. The surface properties of these polymers may be controlled by the ratio of the polylactic acid graft length and copolymer content, and can be potentially used to control the drug release profile and biodistribution. Other examples of this approach include grafting polylactic acid blocks to geraniol and pregnenolone (Kricheldorf and Kreiser-Saunders, 1996). [0235]
  • In some embodiments, the high temperature resorbable material is semi-crystalline and has a melting point of above 100° C. Preferably, the semi-crystalline absorbable is selected from the group consisting of p-dioxanone, L-polylactic acid and poly(glycolic acid) (PGA), and mixtures thereof. [0236]
  • In some embodiments, the strut comprises at last 90 wt % of an aliphatic polyster. Preferably, the aliphatic polyester is polycaprolactone (“PCL”). [0237]
  • Polycaprolactone (PCL) is a linear polyester formed through the ring opening of the monomer epsilon-caprolactone. Polycaprolactone is a semi-crystalline thermoplastic resin, which can be readily molded at moderate temperatures to yield tough translucent products. Its crystalline melting point is about 60° C., which represents a theoretical upper temperature limit of use for the present invention. Above its melting point the material is characterized by a high degree of conformability and workability. [0238]
  • Other polymers such as poly(dodecene-1) and transpolyisoprene are also useful in this invention. These polymers are characterized by being crystalline at room temperature, non-crystalline at about 70° C. and having a relatively rapid rate of crystallization when cooled to body temperature. These polymers do not crystallize like simple compounds so that there is a reasonable time lag after the polymer reaches body temperature before crystallization is complete. This permits sufficient time for the flowable composition to be positioned in the disc space while the polymer is still pliable. [0239]
  • In some embodiments, there is provided an absorbable component comprising a polymer formed from aliphatic lactone monomers selected from the group consisting of p-dioxanone, trimethylene carbonate, ε-caprolactone, glycolide, lactide (l, d, dl, meso), delta-valerolactone, beta-butyrolactone, epsilon-decalactone, 2,5-diketomorpholine, pivalolactone, alpha, alpha-diethylpropiolactone, ethylene carbonate, ethylene oxalate, 3-methyl-1,4-dioxane-2,5-dione, 3,3-diethyl-1,4-dioxan-2,5-dione, gamma-butyrolactone, 1,4-dioxepan-2-one, 1,5-dioxepan-2-one, 1,4-dioxan-2-one, 6,8-dioxabicycloctane-7-one, and combinations thereof. [0240]
  • In one preferred embodiment, the strut comprises a load bearing composition consisting essentially of polycaprolactone. According to Walsh, Biomaterials (2001), 22:1205-1212, the compressive strength of essentially solid polycaprolactone is about 15 MPa, and its compressive modulus is about 0.5 GPa. [0241]
  • In general, the higher molecular weight polycaprolactones (PCLs) are preferred, as they tend to have a higher strength and degrade more slowly. Preferably, the molecular weight of the polycaprolactone is at least 30,000 Daltons. More preferably, the molecular weight of the polycaprolactone is at least 40,000 Daltons. [0242]
  • In one preferred embodiment, the strut comprises a load bearing composition of cross-linked polycaprolactone. The cross-linking of the polycaprolactone should enhance its strength. More preferably, the load bearing composition comprises a self-interpenetrating network (S-IPN) comprising a network of host polycaprolactone and cross-linked polycaprolactone. According to Hao, [0243] Biomaterials (2003), 24:1531-39, the entire teachings of which are incorporated herein by reference, certain mechanical properties of polycaprolactone increased by about 3 fold when it was formed as a S-IPN. When at least 15 wt % HAP was added, the tensile modulus increased to 6 fold over conventional polycaprolactone. If the 3 fold increase in certain mechanical properties reported by Hao would also be realized in compressive strength and compressive modulus, then, the compressive strength of the S-IPN of polycaprolactone may be about 45 MPa, and its compressive modulus may be about 1.5 GPa.
  • In some embodiments, the polycaprolactone is heat treated to enhance its crystallinity, and thereby even further enhance its resistance to degradation. [0244]
  • In yet a further aspect of the present invention, the above described polymers of the present invention may be liquid or low melting temperature, low molecular weight polymers, with or without photocurable groups. The liquid or low melting polymers are of sufficiently low molecular weight, having an inherent viscosity of about 0.05 to about 0.5 dL/g, to yield materials which can easily flow, with or without heat being applied, through a small diameter delivery device such as a syringe or cannula, with or without mechanical assistance, a caulking gun, a soft-sided tube, and the like. [0245]
  • The aliphatic polyesters useful in the practice of the present invention will typically be synthesized by conventional techniques using conventional processes. For example, in a ring opening polymerization, the lactone monomers are polymerized in the presence of an organometallic catalyst and an initiator at elevated temperatures. The organometallic catalyst is preferably tin based, e.g., stannous octoate, and is present in the monomer mixture at a molar ratio of monomer to catalyst ranging from about 10,000/1 to about 100,000/1. The initiator is typically an alkanol, a glycol, a hydroxyacid, or an amine, and is present in the monomer mixture at a molar ratio of monomer to initiator ranging from about 100/1 to about 5000/1. The polymerization is typically carried out at a temperature range from about 80° C. to about 220° C., preferably from about 160° C. to about 200° C., until the desired molecular weight and viscosity are achieved. [0246]
  • Under the above described conditions, the homopolymers and copolymers of aliphatic polyesters, will typically have a weight average molecular weight of about 5,000 grams per mole to about 200,000 grams per mole, and more preferably about 10,000 grams per mole to about 100,000 grams per mole. Polymers of these molecular weights exhibit inherent viscosities between about 0.05 to about 3.0 deciliters per gram (dL/g), and more preferably about 0.1 to about 2.5 dL/g as measured in a 0.1 g/dL solution of hexafluoroisopropanol (HFIP) or chloroform at 25° C. [0247]
  • Suitable lactone monomers used in the matrices of the present invention may be selected from the group consisting of glycolide, lactide (l, d, dl, meso), p-dioxanone, trimethylene carbonate, ε-caprolactone, delta-valerolactone, beta-butyrolactone, epsilon-decalactone, 2,5-diketomorpholine, pivalolactone, alpha, alpha-diethylpropiolactone, ethylene carbonate, ethylene oxalate, 3-methyl-1,4-dioxane-2,5-dione, 3,3-diethyl-1,4-dioxan-2,5-dione, gamma-butyrolactone, 1,4-dioxepan-2-one, 1,5-dioxepan-2-one, 1,4-dioxan-2-one, 6,8-dioxabicycloctane-7-one and combinations of two or more thereof. Preferred lactone monomers are selected from the group consisting of glycolide, lactide, p-dioxanone, trimethylene carbonate and ε-caprolactone. [0248]
  • Most preferably, the aliphatic polyesters used in the matrices of the present invention consist of homopolymers of poly(ε-caprolactone), poly(p-dioxanone), or poly(trimethylene carbonate) or copolymers or mixtures thereof, or copolyesters of p-dioxanone or trimethylene carbonate and glycolide or lactide or mixtures thereof, and in particular, copolymers of p-dioxanone/glycolide, p-dioxanone/lactide, trimethylene carbonate/glycolide and trimethylene carbonate/lactide, or copolyesters of .epsilon.-caprolactone and glycolide or mixtures thereof, or mixtures of homopolymers of ε-caprolactone and lactide. [0249]
  • In a specific embodiment of the present invention, a biocompatible, non-absorbable, flowable polymer whose melting point is from about 45° C. to about 75° C. and which is a rigid solid at body temperatures below about 42° C. is placed in a standard Toomeytype disposable syringe with a 35 mm diameter and appropriate capacity of about 50-100 milliliters. The filled syringe is placed in a peel-apart package for sterile delivery and sterilized with cobalt radiation or heat, the former being preferred. Alternatively, the polymer can be placed in a squeeze bottle of suitable capacity and having a slit orifice. [0250]
  • In some embodiments, the strut comprises at least 90 wt % calcium phosphate. According to Hitchon et al. [0251] J. Neurosurg. (Spine 2) (2001), 95:215-220, the entire teachings of which are incorporated herein by reference, the compressive strength of hydroxyapatite is about 65 MPa and the tensile strength of hydroxyapatite is about 10.6 MPa. The present inventors believe that these values should satisfy typical strut load requirements.
  • In some embodiments, the matrix is made of a cross-linkable compound. In general, cross-linkable compounds cross-link in-situ and provide higher compressive strengths (typically on the order of 20-120 MPa) than heat-flowable polymers (typically on the order of 1-20 MPa. [0252]
  • In some embodiments, the cross-linkable compound comprises an unsaturated linear polyester. [0253]
  • In some embodiments, the unsaturated linear polyester comprises a fumarate double bond, and more preferably comprises polypropylene fumarate. [0254]
  • In some embodiments, the cross-linkable compound is cross-linked by a monomer, preferably a vinyl monomer, more preferably vinyl pyrrolidone. [0255]
  • In some embodiments, the links produced by the cross-linking agent are biodegradable. Preferred embodiments thereof include polypropylene fumarat-diacrylate. [0256]
  • In some embodiments, the cross-linking reaction is aided by an initiator. In preferred embodiments, the initiator is benzoyl peroxide. In other, light is used as the photoinitiator. [0257]
  • In some embodiments, the cross-linking reaction is aided by an accelerant. In preferred embodiments, the accelerant is N,N-Dimethyl-p-toluidine. [0258]
  • It is believed that the terminal functional groups affect the strength and degradation resistance of the cross-linked matrix. In some embodiments, the cross-linked compound is terminated by a terminal group selected from the group consisting of diepoxide, or diacryal functional groups. In preferred embodiments, the terminal groups are diepoxide functional groups. These terminal functional groups were shown to be more resistant to degradation than divinyl terminated polypropylene fumarat (Domb 1996). [0259]
  • In some embodiments, a porogen such as NaCl or a foaming agent is added to the cross-linkable composition. Preferably, the porogen is water soluble, more preferably it is a water soluble salt or sucrose. [0260]
  • In some embodiments, a calcium phosphate based compound, such as hydroxyapatite or tricalcium phosphate, is added to the cross-linkable composition. These compounds are desirable because they can provide an osteoconductive pathway for bone growth, they can neutralize any acid produced from hydrolysis of the polymer matrix, and provide reinforcement. Preferably, the calcium phosphate is nano high aspect hydroxyapatite. [0261]
  • In some embodiments, the strut of the present invention comprises a load bearing composition comprising a fumarate-based polymer (such as polypropylene fumarate) cross-linked with a cross-linking agent containing a polupropylene fumarate-unit, such as polypropylene fumarate-diacrylate. Exemplary compositions are disclosed in Timmer, [0262] Biomaterials (2003) 24:571-577, the entire teachings of which are incorporated herein by reference. These compositions are characterized by a high initial compressive strength (about 10-30 MPa) that typically increases over the first 12 weeks, high resistance to hydrolytic degradation (about 20-50 at 52 weeks), and an acceptable modulus for use as a strut (0.5-1.2 GPa).
  • In preferred embodiments, the polypropylene fumarate: polypropylene fumarate-diacrylate double bond ratio is between about 0.1 and about 3. In more preferred embodiments, the polypropylene fumarate-diacrylate double bond ratio is between about 0.25 and about 1.5. [0263]
  • In more preferred embodiments, the load bearing composition comprising polypropylene fumarate cross-linked by polypropylene fumarate-diacrylate further comprises tricalcium phosphate (TCP), preferably in an amount of between about 0.1 wt % and about 1 wt %. This composition is characterized by a high initial compressive strength (about 30 MPa) that typically increases over the first 12 weeks (to about 45 MPa), a high resistance to hydrolytic degradation (about 45 MPa at 52 weeks), and an acceptable modulus for use as a strut (1.2 GPa at 52 weeks). [0264]
  • In some embodiments, the strut or load bearing composition comprises two cross-linkable polymer compositions. Upon exposure to appropriate cross-linking agents, each of the cross-linkable compositions cross-links with itself, but not with the other cross-linked polymer. The result thereof is a matrix comprising two cross-linked polymers. These are called “interpenetrating networks” (“IPN”). [0265]
  • In other embodiments, the strut or load bearing composition comprises a first cross-linkable polymer composition and a second non-cross linkable polymer composition. Upon exposure to an appropriate cross-linking agent, the first cross-linkable compound cross-links with itself, while the second polymer remains unaffected. The result thereof is a matrix comprising a first cross linked polymer and a second non-cross linked polymers. These are called “semi-interpenetrating networks”(“S-IPN”) [0266]
  • In some embodiments, the S-IPNs comprise a first biodegradable polymer capable of producing acidic products upon hydrolytic degradation; a second biodegradable polymer, which, preferably via crosslinking, provides a biopolymer scaffolding or internal reinforcement; and optionally a buffering compound that buffers the acidic products within a desired pH range. In a preferred embodiment, the second biodegradable polymer comprises polypropylene fumarate (PPF) which is cross-linked, desirably by a vinyl monomer such as vinyl pyrrolidone (VP) to form the biopolymer scaffolding which provides the semi-IPN with the requisite dimensional and geometric stability. A beneficial end use of this material is in the form of internal fixation devices (IFDs) such as bone supports, plates, and pins, and/or bone cements for bone repair which are formed from the semi-IPN alloy disclosed herein. [0267]
  • In some embodiments, the S-IPN comprises a bone cement containing a biodegradable polymeric semi-IPN alloy comprising a first biodegradable polymer (such as PLGA) capable of producing acidic products upon hydrolytic degradation; and a second biodegradable polymer (such as polypropylene fumarate), which provides a biopolymer scaffolding or internal reinforcement, wherein the second biodegradable polymer is polymerized in vivo to provide a hardened, semi-IPN alloy bone cement. Both the bone cement and dimensionally and geometrically stable IFDs of the disclosure of the invention may advantageously also contain other agents such as bone repair proteins (BRPs) and antibiotics, to, e.g., actively promote bone growth and prevent infection while the bone cement or IFD is in place. [0268]
  • In some embodiments, S-IPNs of the present invention include at least two components. The first component is a linear, hydrophobic biodegradable polymer, preferably a homopolymer or copolymer which includes hydroxy acid and/or anhydride linkages or a linear, non-biodegradable hydrophilic polymer, preferably polyethylene oxide or polyethylene glycol. The second component is one or more crosslinkable monomers or macromers. At least one of the monomers or macromers includes a degradable linkage, preferably an anhydride linkage. The linear polymer preferably constituted between 10 and 90% by weight of the composition, more preferably between 30 and 70% of the composition. The crosslinked polymer preferably constitutes between about 30 and 70% by weight of the semi-interpenetrating network composition, more preferably, between 40 and 60 percent of the composition, with the balance being excipients, therapeutic agents, and other components. The compositions form semi-interpenetrating polymer networks when these components are mixed, and the crosslinkable component is crosslinked. Semi-interpenetrating networks are defined as compositions that include two independent components, where one component is a crosslinked polymer and the other component is a non-crosslinked polymer. [0269]
  • These S-IPN compositions can have a viscosity before crosslinking anywhere between a viscous liquid suitable for injection to a moldable, paste-like putty. The viscosity can be adjusted by adding reactive diluents and/or by adding appropriate solvents. When crosslinked, however, the compositions are solid semi-interpenetrating networks, which are capable of supporting, bone growth and repair. [0270]
  • Linear polymers are defined as homopolymers or block copolymers that are not crosslinked. Hydrophobic polymers are well known to those of skill in the art. Biodegradable polymers are those that have a half-life under physiological conditions of between about two hours and one year, preferably less than six months, more preferably, less than three months. Examples of suitable biodegradable polymers include polyanhydrides, polyorthoesters, polyhydroxy acids, polydioxanones, polycarbonates, and polyaminocarbonates. Preferred polymers are polyhydroxy acids and polyanhydrides. Polyanhydrides are the most preferred polymers. [0271]
  • Linear, hydrophilic polymers are well known to those of skill in the art. Non-biodegradable polymers are those that have a half-life longer than approximately one year under physiological conditions. Examples of suitable hydrophilic non-biodegradable polymers include poly(ethylene glycol), poly(ethylene oxide), partially or fully hydrolyzed poly(vinyl alcohol), poly(ethylene oxide)-co-poly(propylene oxide) block copolymers (poloxamers and meroxapols) and poloxamines. Preferred polymers are poly(ethylene glycol), poloxamines, poloxamers and meroxapols. Poly(ethylene glycol) is the most preferred polymer. [0272]
  • The composition includes one or more monomers or macromers. However, at least one of the monomers or macromers includes an anhydride linkage. Other monomers or macromers that can be used include biocompatible monomers and macromers, which include at least one free-radical polymerizable group. For example, polymers including ethylenically unsaturated groups, which can be photochemically crosslinked, may be used, as disclosed in WO 93/17669 by the Board of Regents, University of Texas System, the entire teachings of which are incorporated by reference. [0273]
  • In some embodiments, the cross-linking polymer of the S-IPN comprises a fumarate, preferably polypropylene fumarate. [0274]
  • For the purposes of the present invention, the non-cross-linkable polymer of an S-IPN may also be referred to as a host polymer. In some embodiments, the host polymer for the S-IPN is selected from the group consisting of polylactic acid, polyglycolic acid, and their copolymers. [0275]
  • The present inventors have observed that both Hao and Timmer report significantly greater mechanical properties and resistance to degradation when the host polymer is cross linked by a monomer having the same repeating unit as the host polymer. [0276]
  • In some embodiments, the cross-linkable compound in the S-IPN is cross-linked by N-vinyl pyrrolidone, polyethylene glycol dimethacrylate (PEG-DMA), ethylene dimethacrylate (EDMA), 2-hydroxyethyl methacrylate (HEMA) or methylmethacrylate (MMA). [0277]
  • In some embodiments, a photopolymerized anhydride is used as the matrix material. These materials are characterized as being strong (compressive strength 30-40 MPa), and relatively stiff (tensile modulus of about 600 MPA to about 1400 MPa). [0278]
  • A. K. Burkoth, [0279] Biomaterials (2000) 21:2395-2404, the entire teaching of which are incorporated herein by reference, discloses a number of photopolymerizable anhydrides as suitable for orthopaedic use. The repeating unit of these anhydrides comprises a pair of diacid molecules linked by anhydride bonds that are susceptible to hydrolysis. Because the diacid molecules are hydrophobic, there is a limited diffusion of water into the polymer, and so the polymer is subject only to surface degradation (not bulk degradation). This is advantageous because the strength of the polymer will essentially correspond to the mass of the polymer.
  • In some embodiments, the photopolymerized anhydride is selected from the group consisting of polymers of methacrylated sebacic acid (MSA), methacrylated 1,6-bis(p-carboxyphenoxy) hexane (MCPH), 1,3-bis(p-carboxyphenoxy) propane (CPP), methacrylated cholesterol (MC), methacrylated stearic acid (MstA) and blends and copolymers therefrom. [0280]
  • In some embodiments, the photopolymerization is carried out by adapting a light source to the distal end of the delivery cannula that enters the disc space. In other embodiments, a photo-optic cable is used to transmit light energy into the precursor components that have been deposited in the disc space. In other embodiments, light is transmitted through the skin (i.e, transcutaneously) or through the annulus fibrosus. In some embodiments thereof, a photobleaching initiating system is used. [0281]
  • In some embodiments, a linear polyanhydride is first dissolved in a monomer, and then photopolymerized to form a S-IPN of a photopolymerized anhydride. These are particularly desirable where increased resistance to hydroysis is desired. Accordingly, in some embodiments, the load bearing composition of the present invention comprises a S-IPN comprising a photopolymerized anhydride. [0282]
  • In some embodiments, poly (1,6-bis (p-carboxyphenoxy)hexane (PCPH) is used. This polymer has a degradation of about 496 days, and so is desirably used as the load bearing composition in a strut of the present invention. [0283]
  • Polymerization is preferably initiated using photoinitiators. Photoinitiators that generate an active species on exposure to UV light are well known to those of skill in the art. Active species can also be formed in a relatively mild manner from photon absorption of certain dyes and chemical compounds. [0284]
  • These groups can be polymerized using photoinitiators that generate active species upon exposure to UV light, or, preferably, using long-wavelength ultraviolet light (LWUV) or visible light. LWUV and visible light are preferred because they cause less damage to tissue and other biological materials than UV light. Useful photoinitiators are those, which can be used to initiate polymerization of the macromers without cytotoxicity and within a short time frame, minutes at most and most preferably seconds. [0285]
  • Exposure of dyes and co-catalysts such as amines to visible or LWUV light can generate active species. Light absorption by the dye causes the dye to assume a triplet state, and the triplet state subsequently reacts with the amine to form an active species, which initiates polymerization. Polymerization can be initiated by irradiation with light at a wavelength of between about 200-700 nm, most preferably in the long wavelength ultraviolet range or visible range, 320 nm or higher, and most preferably between about 365 and 514 nm. [0286]
  • Numerous dyes can be used for photopolymerization. Suitable dyes are well known to those of skill in the art. Preferred dyes include erythrosin, phloxime, rose bengal, thonine, camphorquinone, ethyl eosin, eosin, methylene blue, riboflavin, 2,2-dimethyl-2-phenylacetophenone, 2-methoxy-2-phenylacetophenone, 2,2-dimethoxy-2-phenyl acetophenone, other acetophenone derivatives, and camphorquinone. Suitable cocatalysts include amines such as N-methyl diethanolamine, N,N-dimethyl benzylamine, triethanol amine, triethylamine, dibenzyl amine, N-benzylethanolamine, N-isopropyl benzylamine. Triethanolamine is a preferred cocatalyst. [0287]
  • Photopolymerization of these polymer solutions is based on the discovery that combinations of polymers and photoinitiators (in a concentration not toxic to the cells, less than 0.1% by weight, more preferably between 0.05 and 0.01% by weight percent initiator) will crosslink upon exposure to light equivalent to between one and three mWatts/cm.sup.2 applied to the skin of nude mice. [0288]
  • In some embodiments, the matrix comprises a co-polymer having shape memory qualities. In preferred embodiments, the shape memory polymer comprises a first crosslinkable monomer and a second monomer having shape memory qualities. Preferably, the linear polyester has a molecular weight of at least 10,000. Preferably, the first monomer is a linear polyester. Preferably, the second shape memory monomer is n-butyl acrylate. Preferably, cross-linking is induced without an initiator. [0289]
  • Preferably, the shape memory polymer comprises between about 70 wt % and about 90 wt % of the first crosslinkable monomer and between 10 and 30 wt % of the a second monomer having shape memory qualities. [0290]
  • Preferably, the shape memory polymer matrix has a compressive strength of at least 15 MPa. This would make it a suitable candidate as a load bearing composition in a strut of the present invention. [0291]
  • Representative shape memory matrices are disclosed in Lendlein, [0292] PNAS, 98(3), Jan. 30, 2001, pp. 842-7, the entire teachings of which are incorporated herein by reference, which discloses polycaprolactone as the first linear polyester. In other embodiments, polylactic acid is the first linear polyester. It is believed that polylactic acid would provide a strong, stiffer matrix, more suitable for use as a load bearing composition in the strut of the present invention.
  • In one embodiment, the S-IPN comprises: [0293]
  • a) a first part comprising a first bioerodible polymer capable of producing acidic products upon hydrolytic degradation, and [0294]
  • b) a second part comprising a second bioerodible scaffolding polymer, which upon crosslinking provides a biopolymeric scaffolding or internal reinforcement for the S-IPN, and a crosslinking agent for the second bioerodible scaffolding polymer. [0295]
  • In more preferred embodiments, the S-IPN comprises: [0296]
  • a) a first part comprising a first bioerodible polymer capable of producing acidic products upon hydrolytic degradation, a crosslinking initiator, and preferably, a therapeutically effective amount of a biologically active or therapeutic agent and a combination of citric acid and sodium bicarbonate; and [0297]
  • b) a second part comprising a second bioerodible scaffolding polymer, which upon crosslinking provides a biopolymeric scaffolding or internal reinforcement for the S-IPN, and a crosslinking agent for said second bioerodible scaffolding polymer. [0298]
  • In general, many of the resorbable materials are believed to have only moderate strength and stiffness. Therefore, it may be desirable to increase the strength and stiffness of the strut's matrix material by adding reinforcements to the matrix. Although the fibers can be made of non-resorbable materials (such as chopped carbon fibers), preferably the reinforcements are made of materials that are also resorbable. [0299]
  • In some embodiments, the fiber comprises carbon fiber. Preferably, carbon fiber comprises between about 1 vol % and about 60 vol % (more preferably, between about 10 vol % and about 50 vol %) of the load bearing composition. In some embodiments, the polymer and carbon fibers are homogeneously mixed. In others, the material is a laminate. In some embodiments, the carbon fiber is present as chopped state. Preferably, the chopped carbon fibers have a median length of between 1 mm and 12 mm, more preferably between about 4.5 mm and about 7.5 mm. In some embodiments, the carbon fiber is present as continuous strands. [0300]
  • Biodegradable polymers are known, commercially available, or can be synthesized into fibers using known and published methods. Examples of polymers useful in the present invention include poly(L-lactic acid), poly(D,L-lactic acid), poly(D L-lactic-co-glycolic acid), poly(glycolic acid), poly(epsilon-caprolactone), polyorthoesters, and polyanhydrides. These polymers may be obtained in or prepared to the molecular weights and molecular weight distribution needed for service as either the matrix polymer or the pore-forming polymer by processes known in the art. Preferred polymers are poly(alpha-hydroxy esters). Suitable solvent systems are known in the art and are published in standard textbooks and publications. See, for example, Lange's Handbook of Chemistry, Thirteenth Edition, John A. Dean, (Ed.), McGraw-Hill Book Co., New York, 1985, the entire teachings of which are incorporated herein by reference. These polymers may be formed into fibers and webs by standard processing techniques including melt extrusion and spin casting, and are commercially available in woven or non-woven form. [0301]
  • In some embodiments, p-dioxanone fibers are used as the reinforcing phase of the strut. These fibers are advantageous because the high melting point of p-dioxanone resists any thermal degradation of the fibers during injection into the disc space. [0302]
  • In some preferred embodiments, the strut compositions comprise aliphatic polyesters reinforced with p-dioxanone fibers. In more preferred embodiments, those compositions disclosed in U.S. Pat. No. 6,147,135 by Yuan (hereinafter “Yuan”), the specification of which is incorporated herein by reference in its entirety, are selected. [0303]
  • In some embodiments, both the osetobiologic composition and the strut are bioresorbable. The selection of a bioresorbable strut is advantageous because it reduces the amount of foreign materials left in the body. [0304]
  • In some embodiments load-bearing component is used alone. [0305]
  • If desired, the strut material can also include bone growth materials, such as growth factors and stem cells that promote bone growth upon eventual resorption of the resorbable strut. However, since the stem cells must typically be housed in an aqueous phase (such as a hydrogel), the inclusion of stem cells likely requires the introduction of a porosity into the strut that may significantly degrade the strength of the strut. Since the primary purpose of the strut is to support the disc space while the osteogeneic composition promotes fusion, adding stem cells to the strut composition may not be fully desirable in all circumstances. Therefore, in preferred embodiments, only growth factors are added to the strut composition. [0306]
  • In one embodiment, the growth factors are first provided in an aqueous solution and particles of the resorbable strut material are added to the solution. The growth factors cling to the outer surface of the particles. Next, the growth factor-laden particles are separated from the growth factor solution. Next, the growth factor-laden particles are added to the viscous resorbable material. [0307]
  • In some embodiments, the device of the present invention has at least one of the following characteristics: [0308]
    Desired Range Typical Range
    Specification of Values of Values
    Ultimate Load   >5 kN 5-25 kN
    in Axial Compression
    Stiffness   >5 kN/mm 5-25 kN/mm
    in Axial Compression
    Ultimate Load   >2 kN  2-6 kN
    in Compression Shear
    Stiffness   >3 kN/mm  3-9 kN/mm
    in Compression Shear
    Ultimate Load   >5 N-m 5-20 N-m
    in Static Torsion
    Stiffness >>1 kN/mm  1-4 kN/mm
    in Compression Shear
  • In some embodiments, the material comprising the strut of the present invention has at least one of the following intrinsic properties: [0309]
    More
    Intrinsic Property Preferred Value Preferred Value
    Compression Strength   >11 MPa   >25 MPa
    Fracture Strength   >20 MPa   >40 MPa
    Compression Modulus 0.1-10 GPa 0.5-2 GPa
  • In some embodiments, the strut device of the present invention has at least one of the following mechanical performance characteristics: [0310]
    Mechanical Property Preferred Value More Preferred Value
    Static Compressive Load >2 kN >4 kN
    Cyclic Comp. Load (106 cycles) >1 kN >2 kN
  • One example of this embodiment is shown in FIGS. [0311] 2(f) and (g). The arcuate shape has a thickness (t) of 3 mm, inner radius (ri) of 22 mm, an outer radius (ro) of 25 mm and an average height if 15 mm. When this device is produced from a photopolymerized polyanhydride with an intrinsic compressive strength of 30 MPa and compressive modulus of 1 GPa, the static compressive load required to fail the device is 6.6 kN and the compressive stiffness is 15 kN/mm.
  • In some embodiments, the novel struts of the present invention can be used with conventional osteobiologic materials, such as platelet-rich plasma (PRP), allograft particles (such as demineralized bone matrix (DBM) and cancellous chips) and autograft. [0312]
  • In preferred embodiments, the osteobiologic component of the present invention acts in a manner similar to the cancellous core of a vertebral body. Desirable features for the osteobiologic composition of the strut are as follows: [0313]
  • a) strength similar to that of cancellous bone; [0314]
  • b) stiffness similar to that of cancellous bone (or, in relatively large footprint embodiments, cortico-cancellous bone); [0315]
  • c) mild degradation resistance (e.g., degrades in manner that allows bone growth therethrough; and [0316]
  • d) resorbable. [0317]
  • As noted above, in preferred embodiments, the in-situ formed osteobiologic composition comprises: [0318]
  • a) a matrix material (preferably, a polymer flowable at between 40° C. and 80° C.; a linear anhydride, or a fumarate, [0319]
  • b) osteogenenic component (preferably, mesenchymal stem cells present in a concentrated amount), and [0320]
  • c) an osteoinductive factors (preferably, a bone morphogenetic protein). [0321]
  • Examples of matrices that could be used in the osteobiologic component include ceramics comprising calcium phosphate such as, for example, hydroxyapatite or tri-calcium phosphate, polylactic acid, polyglycolic acid, polygalactic acid, polycaprolactone, polyethylene oxide, polypropylene oxide, polysulfone, polyethylene, and polypropylene, hyaluronic acid, which may be purified with or without crosslinking, bioglass, gelatin and collagen. [0322]
  • Preferably, the matrix is a resorbable composition that resorbs within a 2-4 month time period after in-situ formation and comprises: [0323]
  • a) a polymer phase that flows or softens at a temperature of between 40° C. and 80° C. (more preferably, comprising an aliphatic polyester such as polycaprolactone) and is preferably present in an amount of between 50 vol % and 70 vol % of the osteobiologic composition, and [0324]
  • b) an osteoconductive calcium phosphate phase (more preferably hydroxyapatite) preferably present in an amount of between 10 vol % and 30 vol % of the osteobiologic composition. [0325]
  • Optionally, a reinforcing phase (preferably, resorbable polymeric chopped fiber) is also preferably present in an amount of between about 10 vol % and about 30 vol % of the osteobiologic composition. [0326]
  • Preferably, the osteogenic component comprises an aqueous phase (preferably a hydrogel phase) having viable osteoprogenitor cells (preferably mesenchymal stem cells) present therein in a concentrated amount. Preferably, the aqueous phase is present as an interconnected phase throughout the osetobiologic composition, and is present in an amount of between about 25 vol % and about 35 vol % of the osteobiologic composition and has an average diameter of between 100 and 250 μm. [0327]
  • Preferably, the osteoinductive factor is selected from the group consisting of a bone morphogenetic protein and a transforming growth factor. More preferably, the osteoinductive factor is a bone morphogenetic protein. The bone morphogenetic protein may be present in any phase of the osteobiologic composition. When immediate delivery of the bone morphogenetic protein is desirable, the bone morphogenetic protein is present in the hydrogel phase. When intermediate delivery of the bone morphogenetic protein is desirable, the bone morphogenetic protein is present in the polymer phase. When long term delivery of the bone morphogenetic protein is desirable, the bone morphogenetic protein is present in the ceramic phase. It is preferable to have at least twice the autologous level of bone morphogenetic protein, and more preferably, at least 10 times the autologous level of bone morphogenetic protein. [0328]
  • In one preferred embodiment, the matrix comprises a material having a melting point between about 42° C. and about 95° C., (preferably between about 42° C. and about 90° C.) which allows it to be flowed into the disc space without causing tissue necrosis, and then in-situ solidified to provide the needed structural support. The scaffold material further comprises a porogen that allows it to be made into a porous scaffold by conventional leaching techniques. Lastly, growth factors and osteoprogenitor cells such as mesenchymnal stem cells can be flowed through the open porosity of the scaffold to induce bone growth throughout the scaffold. [0329]
  • In another preferred embodiment, mesenchymnal stem cells are isolated from a bone marrow aspirate taken from the patient and incorporated into bioabsorbable particles capable of maintaining cell viability, such as hydrogels. Preferably the hydrogels will absorb quickly such that the cells will be released to form bone. The particulate are then mixed with a scaffold material in a first liquid form that will solidify upon implantation. Preferably, the scaffold material resorbs slowly such that bone can be formed throughout the porosity before the scaffold degrades away. Preferred scaffold materials are polymers that can be dissolved in a cell-friendly solvent such as dimethyl sulfoxide (DMSO), which will leach out once implanted, causing the polymer to precipitate out of solution and create a solid scaffold. Preferably a growth/nutritive factor cocktail for inducing the osteoprogenitor cells to form bone and continue to support the bone formation process is incorporated into the cell-seeded hydrogel as well as the scaffold material. Following disc space preparation the system is injected to the disc space and no other surgical steps are required. [0330]
  • In some aspects of the present invention, there is provided an in-situ formed (and preferably injectable) intervertebral fusion device comprising: [0331]
  • a) a porous scaffold having a porosity suitable for new bone formation, [0332]
  • b) viable osteoprogenitor cells, and [0333]
  • c) osteoinductive factors required to signal the osteoprogenitor cells to form new bone. [0334]
  • Porous scaffolds that can form upon injection through a minimally invasive surgical procedure can be made of a material selected from the group consisting of crosslinked natural and synthetic polymers, low melting point polymers, polymers dissolved in biocompatible solvents, and setting ceramics. Porous scaffolds suitable for use in the present invention are disclosed in U.S. Pat. Nos. 6,280,474 and 6,264,695 (swellable polymers), U.S. Pat. No. 5,888,220 (polycaprolactone/polyurethane), U.S. Pat. No. 6,224,894 (absorbable polyoxaester hydrogels) and U.S. Pat. No. 6,071,982, the entire teachings of the forgoing U.S. patents are incorporated herein by reference. [0335]
  • In many embodiments, the resorbable polymers, calcium phosphates and reinforcing phases disclosed above in the description of the strut may be used to form the preferred matrix. In general, the matrix is substantially weaker (owing to the presence of either open porosity or an interconnected hydrogel phase) than the strut, and hydrolyzes quicker. [0336]
  • In one aspect of the present invention, the matrix has a first absorbable phase of about 1 weight percent to about 99 weight percent of any of the aliphatic homopolyesters of ε-caprolactone, p-dioxanone, or trimethylene carbonate or copolymers or mixtures thereof, with the remaining resorbable phase comprising a bone osteoconductive or osteoinductive calcium containing, non-fibrous, powdered compound, preferably a calcium phosphate such as hydroxyapatite, tri- or tetra-calcium phosphate, or a bioactive glass, or mixtures thereof. [0337]
  • In a further aspect of the present invention, the matrix has a first absorbable phase of about 1 weight percent to about 99 weight percent of aliphatic copolyesters of p-dioxanone or trimethylene carbonate, and glycolide or lactide or mixtures thereof, and in particular, copolymers of p-dioxanone/glycolide, p-dioxanone/lactide, trimethylene carbonate/glycolide and trimethylene carbonate/lactide, with a remaining resorbable phase comprising a bone osteoconductive or osteoinductive calcium containing, non-fibrous, powdered compound, preferably a calcium phosphate such as hydroxyapatite, tri- or tetra-calcium phosphate, or a bioactive glass, or mixtures thereof. [0338]
  • In a further aspect of the present invention, the matrix has a first absorbable phase of about 1 weight percent to about 99 weight percent of aliphatic copolyesters of ε-caprolactone and glycolide or mixtures thereof, or mixtures of homopolymers of ε-caprolactone and lactide, with a remaining resorbable phase comprising a bone osteoconductive or osteoinductive calcium containing, non-fibrous, powdered compound, preferably a calcium phosphate such as hydroxyapatite, tri- or tetra-calcium phosphate, or a bioactive glass, or mixtures thereof. [0339]
  • The above-noted matrices will contain sufficient amounts of the absorbable polymer phase and sufficient amounts of the resorbable second bone regenerating phase to effectively function as bone cements or bone substitutes. Typically, the composites will contain about 1 to about 99 weight percent of polymer phase, and more preferably about 5 to about 95 weight percent. The composites will typically contain about 1 to about 99 weight percent of the bone regenerating phase, and more preferably about 5 to about 95 weight percent. [0340]
  • It will be appreciated by those skilled in the art that the relative amounts of the first absorbable, polymeric phase to the second resorbable phase in the above-noted matrices will depend upon various parameters including, inter alia, the levels of strength, stiffness, and other physical and thermal properties, absorption and resorption rates, setting and hardening rates, deliverability, etc., which are required. The desired properties of the composites of the present invention and their level of requirement will depend upon the body structure area where the bone cement or substitute is needed. Accordingly, the composites of the present invention will typically contain about 1 weight percent to about 99 weight percent, and more preferably about 5 weight percent to about 95 weight percent of aliphatic polyester homo- or co-polymers, or blends thereof. [0341]
  • A further aspect of the present invention is a process by which the matrix component of the osteobiologic composition is prepared. The matrix can be prepared by a one-step or a two-step process in which a bone regenerating material is mixed in the reaction vessel with a just-formed polymer (one-step process), or mixed with a pre-formed polymer in a separate vessel (two-step process). [0342]
  • The composites of the present invention can be manufactured in the following two-step process. The preformed polymers and bone regenerating materials are individually charged into a conventional mixing vessel having a conventional mixing device mounted therein such as an impeller. Then, the polymers and bone substitutes are mixed at a temperature of about 150° C. to about 220° C., more preferably about 160° C. to about 200° C., for about 5 to about 90 minutes, more preferably for about 10 to about 45 minutes, until a uniformly dispersed composite is obtained. Then, the composite is further processed by removing it from the mixing device, cooling to room temperature, grinding, and drying under pressures below atmospheric at elevated temperatures for a period of time. [0343]
  • In addition to the above manufacturing method, the composites can be prepared by a one-step process by charging the bone regenerating material to a reaction vessel which contains the just-formed polymers. Then, the polymers and bone substitutes are mixed at a temperature of about 150° C. to about 220° C., more preferably about 160° C. to about 200° C., for about 5 to about 90 minutes, more preferably for about 10 to about 45 minutes, until a uniformly dispersed composite is obtained. Then, the composite is further processed by removing it from the mixing vessel, cooling to room temperature, grinding, and drying under pressures below atmospheric at elevated temperatures for a period of time. [0344]
  • In other embodiments, the matrix of the present invention includes a bone implant material, which can be readily molded at a selected temperature at or below about 60° C. The material is formed as a cohesive mixture of hard filler particles and a binder composed of a biocompatible, biodegradable thermoplastic polymer having fluid-flow properties at the selected temperature at or below about 60° C. [0345]
  • Any hard biocompatible filler particles, including autogenous bone chips, can be used in this invention. However hydroxyapatite is a preferred filler for its permanance and biological profile. Tricalcium phosphate and glass granules may also be used alone or in combination with hydroxyapatite, particularly if some degree of resorption is desired in the filler. [0346]
  • The binder preferably ranges in fluid-flow properties (flowability) between a highly viscous fluid and a putty-like semi-solid, at the selected temperature. With too low a binder viscosity, the implant material suffers the same problems seen in loose-particle implants: poor shape retention, once molded, and poor cohesiveness, leading to exfoliation of particles before or during the tissue ingrowth period. In a preferred embodiment, the polymer includes polylactic acid having a molecular weight between about 400 and about 5,000 daltons. [0347]
  • The binder preferably constitutes no more than about one-third of the total solid volume of the material, leaving void space in the material, which can accommodate tissue ingrowth. The minimum amount of binder is that necessary to give easy formability and provide sufficient particle cohesion and shape retention during the period of tissue ingrowth. [0348]
  • By similar methods, polylactic acid having progressively greater molecular weights between about 2,000 and about 5,000 daltons were prepared and tested for binder characteristics when formulated with hydroxyapatite particles. Above about 2,000 daltons, the implant material was quite hard and difficult to mold by hand at 40° C., and at 5,000 daltons, temperatures up to about 60° C. were required to achieve moldability. [0349]
  • To form the implant material of the invention, the binder from above is mixed with hydroxyapatite particles, and the components are thoroughly blended. Preferably the material contains some void space, to allow tissue ingrowth independent of polymer breakdown. Since the void space of a mass of spherical particles is about one-third that of the particle mass, the implant material preferably contains less than about one-third by volume of binder. To optimize the void space, the minimum amount of binder needed to produce good particle cohesiveness, typically between about 5% and 20% of the total solid volume of the material, is added. In one embodiment, implant material containing 80% hydroxyapatite particles (average particle size of about 650 microns), and 20% of polylactic acid polymer having average polymer molecular weights of about 1,100 daltons was prepared. The material was easily moldable by hand at 50° C., and showed good cohesiveness and shape retention at 37° C. [0350]
  • In practicing the invention, there is provided a moldable hydroxyapatite bone-implant material. As described above, implant material having a range of molding temperatures and biodegradability can be provided, by adjusting the composition and amount of binder in the material. Material having a relatively high molding temperature, e.g., between about 40° C. to about 60° C., is generally preferred where the implant needs to be in a relatively rigid condition during the process of tissue ingrowth, for example, to prevent significant shape deformation. Here the material is applied and shaped to the bone site in a heated state; after cooling, it assumes the desired rigid condition. [0351]
  • The material can be formulated with thermoplastic polymer binders of various composition and molecular weights, to achieve a selected molding temperature, rigidity in the bone site, and rate of binder breakdown. By varying the relative proportions of binder and particles, selected changes in the void space and cohesiveness of the material are possible. [0352]
  • Matrix scaffold polymers can also be produced by first dissolving the polymer in a biocompatible, water-soluble solvent, injecting the material into the disc space, and then allowing the solvent to leach out of the polymer into the body, thereby causing the polymer to solidify in vivo. Suitable polymers compatible with such solvents include, but are not limited to, poly(lactic acid), poly(glycolic acid) and copolymers therefrom. Suitable biocompatible, water-soluble solvents include dimethylsulfoxide (DMSO). Preferably, the volume ratio of polymer to solvent is at least 1:5, more preferably at least 1:2. By maximizing the amount of polymer in the polymer/solvent injection, the amount of structural material solidified in the body is maximized while minimizing the amount of solvent to be excreted by the body. [0353]
  • Injectable ceramics can also serve as components in the matrix of the osteobiologic component. Preferred injectable, resorbable ceramics are amorphous calcium phosphates or hydroxyapatites. (See U.S. Pat. Nos. 6,214,368 and 6,331,312, the entire teachings of which are incorporated herein by reference.) [0354]
  • In some embodiments of the present invention, porosity is produced in the matrix to produce a porous scaffold material. Once in-situ porosity is produced in the osetobiologic composition, the surgeon can then inject an osteogenic component (such as mesenchymnal stem cells) or an osteoinductive component (such as bone morphogenetic protein) into the porosity, thereby enhancing the ostobiologic nature of the composition. [0355]
  • Providing porosity in-situ allows the matrix of the osteobiologic composition to comprise materials such as polymers that flow at temperatures only well above body temperature. For example, many polymers such as polycaprolactone flow at about 60° C., a temperature that may well destroy the viability of mesenchymnal stem cells contained within the flowable polymer. [0356]
  • Therefore, in some embodiments of the present invention, polymeric materials that become flowable above 45° C. are first made flowable by raising their temperature to at least 45° C., the flowable polymer is then injected into the disc space, the in-situ formed material is then made porous, and porous material is then injected with mesenchymnal stem cells. [0357]
  • In some embodiments of the present invention, in-situ porosity is accomplished by first delivering the matrix material into the disc space as beads, then tightly packing the beads within the disc space, and then bonding the beads, preferably by heat bonding, into a stable structure. [0358]
  • In some embodiments of the present invention, porosity is produced in the matrix to including a foaming agent in the matrix material. [0359]
  • According to another embodiment, porous injectable graft materials are optionally made by adding a degradable gas-producing compound. As gas bubbles are produced from the gas-producing compound, pores are formed in the bone-like materials. The size of the pores are preferably controlled by adjusting the amount of gas-producing compound and the viscosity of the mineral matrix in the fluid used to mix the materials. In a specific embodiment, sodium bicarbonate and/or calcium bicarbonate is added to the flowable matrix material and a precise amount of acid (e.g. citric acid, formic, acetic, phosphoric acids, hydrochloric acid) is added to the mixing fluid. The acidity of the mixing fluid causes carbon dioxide to be released from the sodium bicarbonate, wherein the carbon dioxide ultimately forms pores in the matrix material. In an alternative embodiment, hydrogen peroxide is combined with peroxidase in the graft material. The peroxidase releases oxygen from the hydrogen peroxide, which has the added advantage of sterilizing the wound site. [0360]
  • In some embodiments of the present invention, in-situ porosity can be produced in the matrix material including a porogen with the matrix material, and then in-situ leaching out of the porogen. Preferably, a porogen is a water-soluble materials. Biodegradable materials can be fabricated into three dimensional anatomical shapes having load bearing properties similar to or exceeding that of natural bone. A matrix component of the osteobiologic component has the capability of being rendered porous and can serve to foster bony fusion. In these embodiments, the osteobiologic composition can be implanted without first being rendered to its porous state. Porosity can be achieved after implantation by a faster rate of biodegradation of a pore-forming component of the osteobiologic component relative to a slower rate of degradation of the matrix component of the osteobiologic component. The porous osteobiologic component has sufficient compressive strength and modulus to serve as a bone replacement prosthesis during that period wherein the body regenerates new natural bone within and to the shape of the osteobiologic component. Ultimately, the osteobiologic component is replaced by natural bone as the osteobiologic component biodegrades and by such process is displaced or eliminated from the body by natural processes. [0361]
  • In such embodiments, the osteobiologic composition comprises at least two components, a continuous matrix component and an included pore-forming component. The matrix component comprises a biodegradable material having a rate of degradation, which at least matches the rate at which the body regenerates natural bone tissue. The pore-forming component is a material, which differs from the matrix material such that it may be differentiated from the matrix component and ultimately be removed therefrom by differential dissolution or biodegradation to provide porosity to the prosthetic template either prior to or after implantation. [0362]
  • Unless wholly removed from the matrix polymer of the implant before implantation, the molecular weight, molecular weight distribution and degree of crystallinity of the pore-forming polymer is also of significant concern. Generally, the pore-forming polymer should biodegrade and/or bioresorb at a rate that is at least four times greater than that of the matrix polymer. Further, the pore-forming polymer should have a polydispersity index of at least 3 to provide for a controlled degradation over a period of time that avoids intolerable localized pH concentrations due to its degradation by-products. [0363]
  • The osteobiologic compositions of these embodiments can contain a relatively high ultimate porosity capacity. That is, the osteobiologic composition is fabricated in a manner, which results in an osteobiologic component capable of being rendered highly porous prior to implantation. For example, the matrix may be formed around included particles or fibers which particles or fibers are subsequently removed from the matrix by solvent dissolution or other methods of degradation, leaving a highly porous matrix scaffold structure. Alternatively, the particles or fibers embedded within the formed matrix may be retained in the osteobiologic composition for dissolution or degradation in situ after implantation. In addition, portions of the pore-creating material may be removed prior to implantation of the osteobiologic composition providing a range of actual to ultimate porosities of the implantable osteobiologic components. [0364]
  • The ultimate porosity capacity may be defined as the percent porosity of the matrix after at least 90% of the pore forming material has been removed from the template, either in vitro or in vivo. In the present invention, it is preferred that the ultimate porosity capacity of the biodegradable/bioresorbable osteobiologic component be in the range of between about 20% and about 50% volume of the osteobiologic component. [0365]
  • The biodegradable osteobiologic composition of the present invention, which has the porogen features described above, including high mechanical strength necessary for replacement of load bearing bones, high ultimate porosity capacity to permit bony fission therethrough, and a rate of degradation approximately matching the rate of new tissue growth may, for example, be formed by the methods described below. In its simplest embodiment, these osteobiologic compositions of the present invention are formed by distributing within a polymeric matrix a pore-creating substance (or “porogen”). Regardless of the specific methods used to form the osteobiologic composition, the product will include a three-dimensional, anatomically-shaped osteobiologic composition having a high ultimate porosity capacity due to the presence of a pore creating substance dispersed within the matrix. [0366]
  • The pore creating substance may be formed for example of salts, polysaccharides, protein, polymers other than the matrix polymers, or other non-toxic materials such as gelatin which are, for example, soluble in a solvent which does not dissolve the matrix polymer; made fluid at a higher glass transition temperature (Tg) or melting temperature (Tm) than the matrix polymer; or otherwise differentiated from the matrix polymer so as to retain an independent structure from the polymeric matrix. When subsequently removed, the desired pores are formed within the matrix. [0367]
  • The temperature required to fluidize polymers is that which permits non-hindered flow of polymer chains. For amorphous polymers, this “flow temperature” is the glass transition temperature (Tg). However, for semi-crystalline polymers this “flow temperature” is the melting temperature (Tm). As used herein, flow temperature is meant to be that temperature which permits non-hindered flow of polymer chains and includes, as appropriate, Tg for amorphous polymers and Tm for at least semi-crystalline polymers. [0368]
  • The pore creating substance may be in the form of particles such as salt, which after forming a matrix in which the particles have been included, the particles are leached out or otherwise removed from the matrix leaving a polymeric matrix with high porosity. The pore creating substance may be in the form of fibers such as polymeric fibers or webs dispersed within a formed polymeric matrix. The dispersed fibers and the surrounding matrix possess differential rates of degradation, with the fibers being degraded at a faster rate than the matrix, thereby being removed from the osteobiologic composition and creating a highly porous polymeric, osteobiologic composition. [0369]
  • The porogen-containing osteobiologic composition may be formed by dispersing the pore-creating substance in a body of powdered polymer. Preferably, the pore-creating substance is a first polymer in fiber or web form dispersed in a body of powdered second polymer. The second polymer has a lower flow temperature (Tf) such that when the dispersion is heated above the flow temperature of the powder, the powder is fluid, but the dispersed fibers are not. The fluid polymer is next solidified, e.g., by permitting the dispersion to return to ambient temperature, resulting in a polymeric matrix having entrapped therein the pore-forming substance. [0370]
  • In a preferred embodiment, a first polymer is used to form the matrix and a second polymer is used to form the pore-creating substance dispersed within the first polymer. Both first and second polymers are biodegradable but the second degrades at a faster rate than the first polymer, e.g., approximately two to eight times faster, and preferably about four times faster creating the desired porous body for ingrowth and proliferation of cells. For example, poly(glycolic acid) (PGA) fiber meshes may be dispersed within poly(L-lactic acid) (PLLA). Upon curing of the PLLA matrix, the PGA fiber mesh is embedded within the PLLA matrix. The PGA fibers biodegrade at a more rapid rate than PLLA, thus creating a template having a high ultimate porosity capacity. [0371]
  • The pore creating substance may be formed of a low molecular weight polymer while the matrix is formed of a high molecular weight polymer. Because the low molecular weight polymers degrade at a faster rate than the high molecular weight polymers an implant having a desired rate of degradation of each of the pore creating substance and the matrix can be formed. [0372]
  • In vivo degradation of the pore-creating substance at a faster rate than the template matrix, such as PGA fibers which degrade within months of implantation in a PLLA matrix which may take more than one year to degrade, permits gradual replacement of the pore-creating substance with growing bone cells. The resorbing pore-creating substance is gradually replaced with newly formed bone tissue, maintaining a mechanically strong bone prosthesis. The more slowly degrading polymeric matrix is then resorbed and replaced with bone tissue proliferating from the network of growing tissue already present throughout the prosthetic template. [0373]
  • In some embodiments, the matrix has a sufficient number of pores or passageways so that the total accessible surface area of the substrate is at least five times greater than a solid object having the same external dimensions. Thus, the preferred total surface area can be achieved by using a substrate, which comprises a mass of powder, a mass of granules, a mass of fibers, or a highly porous block of substrate material. Preferably, the average pore size in the matrix is greater that 20 μm, more preferably greater than 50 μm, more preferably greater than 100 μm. In some embodiments, the pore size is between about 100 μm and 250 μm. [0374]
  • The osteobiologic compositions of the present invention have a high ultimate porosity capacity, resulting in a highly porous matrix containing a uniformly distributed and interconnected pore structure. Pore volume of the porous osetobiologic composition is approximately 20% to 90%, and the average pore diameter is approximately 50 to 250 μm. The pore volume and diameter also directly relate to the rate of tissue ingrowth and matrix degradation. The porous matrix of the present invention accommodates large number of cells adhering to the matrix, permits cells to be easily distributed throughout the template, and allows an organized network of tissue constituents to be formed. The matrix preferably promotes cell adhesion and permits the attached cells to retain differentiated cell function. In some embodiments, the leachate produces an open porosity having an average pore size of between 20 μm and 500 μm, preferably 50-250 μm. This range is preferred for bone growth. [0375]
  • In some embodiments, the matrices of the osteobioloigic component are fabricated of polymers and by methods which result in implants which are capable of being rendered porous for tissue ingrowth while retaining sufficient mechanical strength to be suitable for supporting a disc space. For example, in their preporous state the osteobiologic compositions of the present invention possess a compressive strength of approximately 5 MPa to 50 MPa and a compressive modulus of approximately 50 MPa to 500 MPa as tested by an Instron Materials Testing Machine according to American Society for Testing and Materials (ASTM) Standard F451-86. The values of 5 MPa compressive strength and 50 MPa compressive modulus correspond to the mid-range values for human trabecular bone. [0376]
  • The biodegradable, bioresorbable matrices of the present invention preferably are formed of polymeric materials, the matrix polymer having a rate of degradation which is matched to the rate of tissue in-growth. The matrix polymeric substance preferably ranges in weight average molecular weight from approximately 50,000 to 200,000. Crystallinity of the matrix polymer of implant is approximately 0 to 25%. The molecular weight and molecular weight distribution of the matrix polymer is related to the rate at which the matrix biodegrades. In a matrix of broad molecular weight distribution, e.g., having a polydispersity index (Mw/Mn) greater than 2 fractions of the material exist in short to long polymeric chains. This diversity allows a continuation of degradation over time without sharp changes, e.g., in pH due to degradation products, as may occur with a material having a narrow molecular weight distribution. In the present invention, the polydispersity index of the matrix is preferably in the range of 3-6. [0377]
  • In some embodiments possessing in-situ created porosity, mesenchymnal stem cells (“MSCs”) are then delivered into the porous matrix. [0378]
  • In some embodiments, the mesenchymnal stem cells are delivered into the porosity of the scaffold by simply directing an aqueous solution containing mesenchymnal stem cells into the scaffold. In some embodiments, an additional cannula can be placed near the porous matrix to serve as an exit cannula for the fluid. [0379]
  • In some embodiments, a hydrophilic matrix material such as polylactic acid may be used. In these instances, it has been found that mesenchymnal stem cells do not tenaciously adhere to the surface of the polylactic acid. Accordingly, in some embodiments, a lining material, such as hydroxyapatite (HA), may be used to line the inner surface of the scaffold with a material to which mesenchymnal stem cells more tenaciously adhere. In some embodiments, the linings disclosed in U.S. Pat. No. 5,133,755 by Brekke, the entire teachings of which are incorporated herein by reference (hereinafter “Brekke”), are selected. [0380]
  • In some embodiments, other cell adhesion molecules may be bound to the inner surface of the matrix in order to enhance the adhesion of the mesenchymnal stem cells to the scaffold. The term “cell adhesion molecules” refers collectively to laminins, fibronectin, vitronectin, vascular cell adhesion molecules (V-CAM), intercellular adhesion molecules (I-CAM), tenascin, thrombospondin, osteonectin, osteopontin, bone sialoprotein, and collagens. [0381]
  • Preferably, the mesenchymnal stem cells are delivered into the in-situ porosity under pressure, such as by injection. In these cases, it is helpful to surround the porous osteobiologic composition with a containing envelope in order to contain the osteogenic component within the in-situ porosity and prevents its leakage outside the osteobiologic composition. [0382]
  • In some embodiments, the envelope is the strut component having a 360 degree span. In other embodiments, the envelope can be an inflatable device component of the osteobiologic composition. [0383]
  • Although it may be useful to create in-situ porosity, it may sometimes be problematic to evenly distribute the mesenchymnal stem cells throughout the in-situ created porosity under normal injection pressures. In some embodiments of the present invention, the mesenchymnal stem cells are delivered into the in-situ porosity under a higher pressure that is sufficient to fill 90% of the porosity. Preferably, the pressure is high enough to completely fill the porosity. [0384]
  • Therefore, in accordance with the present invention, there is provided a method delivering an osteogenic component, comprising the steps of: [0385]
  • a) injecting an osteobiologic composition into a disc space, [0386]
  • b) creating in-situ porosity in the osteobiologic component, and [0387]
  • c) delivering an osteogenic component into the in-situ porosity under a pressure of at least sufficient to fill at least 90% of the porosity. [0388]
  • In some embodiments of the present invention, the osteobiologic component of the present invention further comprises a gelled aqueous phase, wherein viable mesenchymnal stem cells are located in the aqueous phase. [0389]
  • Because mesenchymnal stem cells (and many growth factors) are very heat sensitive, it is desirable to deliver mesenchymnal stem cells and growth factors at or near body temperature. However, many of the bioabsorbable polymers are flowable at temperatures well in excess of body temperature. Similarly, many cross-linked polymers experience an exotherm of over 100° C. It is not known whether mesenchymnal stem cells and growth factors could remain viable after prolonged exposure to these temperatures. [0390]
  • Since calcium phosphate can be made flowable at body temperature, it is desirable to select an osteobiologic composition having a matrix comprising calcium phosphate when also choosing to deliver the mesenchymnal stem cells or growth factors to the disc space during the delivery of the matrix component of the osteobiologic composition. [0391]
  • Therefore, in some embodiments there is provided an osteobiologic composition that is flowable at body temperature, the composition comprising a matrix comprising calcium phosphate and an osteogenic component. [0392]
  • Hydrogels are useful in this respect because they can adequately protect bone growth cells contained therein. [0393]
  • A “hydrogel” is a substance formed when an organic polymer (natural or synthetic) is set or solidified to create a three-dimensional open-lattice structure that entraps molecules of water or other solution to form a gel. The solidification can occur, e.g., by aggregation, coagulation, hydrophobic interactions, or cross-linking. The hydrogels employed in this invention rapidly solidify to keep the cells at the application site, thereby eliminating problems of phagocytosis or cellular death and enhancing new cell growth at the application site. The hydrogels are also biocompatible, e.g., not toxic, to cells suspended in the hydrogel. [0394]
  • A “hydrogel-cell composition” is a suspension of a hydrogel containing desired tissue precursor cells. These cells can be isolated directly from a tissue source or can be obtained from a cell culture. A “tissue” is a collection or aggregation of particular cells embedded within its natural matrix, wherein the natural matrix is produced by the particular living cells. [0395]
  • The hydrogel-cell composition forms a uniform distribution of cells with a well-defined and precisely controllable density. Moreover, the hydrogel can support very large densities of cells, e.g., 50 million cells/ml. These factors improve the quality and strength of the new tissue. In addition, the hydrogel allows diffusion of nutrients and waste products to, and away from, the cells, which promotes tissue growth. [0396]
  • Hydrogels suitable for use in the osteobiologic composition of the present invention are water-containing gels, i.e., polymers characterized by hydrophilicity and insolubility in water. See, for instance, “Hydrogels”, pages 458-459 in Concise Encyclopedia of Polymer Science and Engineering, Eds. Mark et al., Wiley and Sons, 1990, the disclosure of which is incorporated herein by reference. Although their use is optional in the present invention, the inclusion of hydrogels is highly preferred since they tend to contribute a number of desirable qualities. By virtue of their hydrophilic, water-containing nature, hydrogels generally can: [0397]
  • a) house mesenchymal stems cells, [0398]
  • b) assist the cured composite with load bearing capabilities of the cured composite, and [0399]
  • c) decrease frictional forces on the composite and add thermal elasticity. [0400]
  • Suitable hydrogels generally exhibit an optimal combination of such properties as compatibility with the matrix polymer of choice, and biocompatability. [0401]
  • Where the osteobiologic composition is delivered in conjunction with a strut and therefore is no longer required to bear the majority of loads on the spinal treatment site, the hydrogel phase is preferably between about 50 and about 90 volume percent of the total volume, more preferably between about 70 and about 85 volume percent. [0402]
  • In some embodiments wherein the osteobiologic component is a stand-alone component (i.e., there is essentially no strut), the osetobiologic composition will preferably contain a hydrogel phase at a concentration of between about 15 and 50 volume percent, and preferably between about 20 and about 30 volume percent of the osteobiologic composition. The lower levels of the hydrogel phase provide additional opportunity to use a strong matrix in the osteobiologic component. [0403]
  • Polymer-hydrogel composites demonstrate an optimal combination of physical/chemical properties, particularly in terms of their conformational stability, resorption characteristics, biocompatability, and physical performance, e.g., physical properties such as density, thickness, and surface roughness, and mechanical properties such as load-bearing strength, tensile strength, static shear strength, fatigue of the anchor points, impact absorption, wear characteristics, and surface abrasion. [0404]
  • In general, an unsupported hydrogel is not sufficiently stiff or strong to survive the high spinal loads experienced during the fusion process. Accordingly, in many embodiments of the present invention, the hydrogel is supported not only by the strut component of the present invention, but also by the matrix component of the osteobiologic component. In these cases, the hydrogel is either delivered into the disc space along with the matrix component (as is preferred when the matrix component of the osteobiologic component comprises CaPO[0405] 4), or is delivered after in-situ porosity has been produced in the matrix component of the osteobiologic component (as with flowable polymers).
  • However, in some embodiments, the strut component of the present invention may span a sufficiently large portion of the disc space and have sufficient stiffness to adequately support and contain the hydrogel phase within the disc space without the need of a supplemental matrix in the osetobiologic component. In these embodiments, the strut component preferably describes an arc of at least 200 degrees about the disc space, more preferably at least 270 degrees, more preferably at least 350 degrees, and most preferably is about 360 degrees. Such struts are exemplified in FIGS. [0406] 2(a) through (e), FIGS. 4(a) and (b) and FIGS. 5(a) and (b).
  • Therefore, in accordance with the present invention, there is provided an intervertebral body fusion device, comprising: [0407]
  • a) an in situ produced load bearing strut having a shape that spans at least 200 degrees, and [0408]
  • b) an osteobiologic component consisting essentially of: [0409]
  • an aqueous phase comprising an osteogenic component. [0410]
  • The hydrogel can include any of the following: polysaccharides, proteins, polyphosphazenes, poly(oxyethylene)-poly(oxypropylene) block polymers, poly(oxyethylene)-poly(oxypropylene) block polymers of ethylene diamine, poly(acrylic acids), poly(methacrylic acids), copolymers of acrylic acid and methacrylic acid, poly(vinyl acetate), and sulfonated polymers. [0411]
  • In general, these polymers are at least partially soluble in aqueous solutions, e.g., water, or aqueous alcohol solutions that have charged side groups, or a monovalent ionic salt thereof. There are many examples of polymers with acidic side groups that can be reacted with cations, e.g., poly(phosphazenes), poly(acrylic acids), and poly(methacrylic acids). Examples of acidic groups include carboxylic acid groups, sulfonic acid groups, and halogenated (preferably fluorinated) alcohol groups. Examples of polymers with basic side groups that can react with anions are poly(vinyl amines), poly(vinyl pyridine), and poly(vinyl imidazole). [0412]
  • Water soluble polymers with charged side groups are cross-linked by reacting the polymer with an aqueous solution containing multivalent ions of the opposite charge, either multivalent cations if the polymer has acidic side groups, or multivalent anions if the polymer has basic side groups. Cations for cross-linking the polymers with acidic side groups to form a hydrogel include divalent and trivalent cations such as copper, calcium, aluminum, magnesium, and strontium. Aqueous solutions of the salts of these cations are added to the polymers to form soft, highly swollen hydrogels. [0413]
  • Anions for cross-linking the polymers to form a hydrogel include divalent and trivalent anions such as low molecular weight dicarboxylate ions, terepthalate ions, sulfate ions, and carbonate ions. Aqueous solutions of the salts of these anions are added to the polymers to form soft, highly swollen hydrogels, as described with respect to cations. [0414]
  • For purposes of preventing the passage of antibodies into the hydrogel, but allowing the entry of nutrients, a useful polymer size in the hydrogel is in the range of between 10,000 D and 18,500 D. Smaller polymers result in gels of higher density with smaller pores. [0415]
  • Ionic polysaccharides, such as alginates or chitosan, can be used to suspend living cells. In one example, the hydrogel is produced by cross-linking the anionic salt of alginic acid, a carbohydrate polymer isolated from seaweed, with ions, such as calcium cations. The strength of the hydrogel increases with either increasing concentrations of calcium ions or alginate. For example, U.S. Pat. No. 4,352,883 describes the ionic cross-linking of alginate with divalent cations, in water, at room temperature, to form a hydrogel matrix. [0416]
  • Tissue precursor cells are mixed with an alginate solution, the solution is delivered to an already implanted support structure and then solidifies in a short time due to the presence in vivo of physiological concentrations of calcium ions. Alternatively, the solution is delivered to the support structure prior to implantation and solidified in an external solution containing calcium ions. [0417]
  • In some embodiments, the hydrogel comprises alginate. Alginate can be gelled under mild conditions, allowing cell immobilization with little damage. Binding of Mg[0418] 2+ and monovalent ions to alginate does not induce gelation of alginate in aqueous solution. However, exposure of alginate to soluble calcium leads to a preferential binding of calcium and subsequent gelling. These gentle gelling conditions are in contrast to the large temperature or solvent changes typically required to induce similar phase changes in most materials.
  • Alginates have been utilized as immobilization matrices for cell, as an injectable matrix for engineering cartilaginous tissue to treat vesicoureteral reflux in various animal models, and as injectable microcapsules containing islet cells to treat animal models of diabetes. [0419]
  • The open lattice structure and wide distribution of pore sizes in calcium alginate preclude the controlled release of large molecules (e.g., proteins) from these materials and limits the use of pure alginate for entrapment of whole cells or cell organelles. However, alginate membrane can be modified by incorporating other polymeric elements (e.g., lysine, poly(ethylene glycol), poly(vinyl alcohol) or chitosan). These modified systems have been used to control the release of proteins from alginate beads. Haemostatic swabs made of calcium alginate have also been clinically utilized to reduce blood loss during surgical procedures. The calcium ions in alginate may assist the blood clotting process by activating platelets and clotting factor VII. [0420]
  • Collagen-polysaccharide-hydroxyapatite compositions suitable for a matrix of the present invention have been disclosed by Liu in U.S. Pat. No. 5,972,385, the entire teachings of which are incorporated herein by reference. A polysaccharide is reacted with an oxidizing agent to open sugar rings on the polysaccharide to form aldehyde groups. The aldehyde groups are reacted to form covalent linkages to collagen. [0421]
  • The type of polysaccharides which can be used include hyaluronic acid, chondroitin sulfate, dermatan sulfate, keratan sulfate, heparan, heparan sulfate, dextran, dextran sulfate, alginate, and other long chain polysaccharides. In a preferred embodiment, the polysaccharide is hyaluronic acid. [0422]
  • A crosslinked collagen-polysaccharide matrix of the present invention may be used alone to conduct the growth of tissue; in combination with a growth factor to induce the growth of tissue; in combination with fibrin to anchor the matrix into sites of tissue defect, or in combination with both growth factor and fibrin. [0423]
  • The method of making a collagen-polysaccharide matrix of the present invention comprises the steps of oxidizing an exogenous polysaccharide to form a modified exogenous polysaccharide having aldehyde groups, and reacting the modified exogenous polysaccharide with collagen under conditions such that the aldehyde groups covalently react with collagen to form a crosslinked matrix. The method may further comprise the step of adding a growth factor to the matrix. A growth factor can be added before or after the step of reacting the modified polysaccharide with the collagen. [0424]
  • The fibrin used in a crosslinked collagen-polysaccharide matrix of the present invention is prepared by contacting a preformed matrix with a source of fibrinogen and thrombin or by combining the fibrinogen and thrombin with the modified exogenous polysaccharide and collagen at the time of reaction. Alternately, fibrinogen and thrombin in a collagen polysaccharide matrix may be added to another preformed collagen polysaccharide matrix. Therefore, the present invention also comprises a method for preparing a crosslinked collagen-polysaccharide matrix comprising fibrin. [0425]
  • In other embodiments, the hydrogel comprises a microbial polysaccharide. Microbial polysaccharides are ubiquitous in nature and very abundant biopolymers. They are of interest because of their unusual and useful functional properties. Some of these properties are summarized as follows: (i) film-forming and gel-forming capabilities, (ii) stability over broad temperature ranges, (iii) biocompatibility (natural products avoid the release/leaching of toxic metals, residual chemicals, catalyst, or additives), (iv) unusual rheological properties, (v) biodegradability, (vi) water solubility in the native state or reduced solubility if chemically modified, and (vii) thermal processability for some of these polymers. It is worthy to note that gellan, one of the microbial polysaccharides, has been investigated as immobilization materials for enzymes and cells. [0426]
  • In some embodiments, the hydrogel is a synthetic hydrogel. One synthetic hydrogel is polyphosphazene. Polyphosphazenes contain inorganic backbones comprised of alternating single and double bonds between nitrogen and phosphorus atoms, in contrast to the carbon-carbon backbone in most other polymers. The uniqueness of polyphosphazenes stems from the combination of this inorganic backbone with versatile side chain functionalities that can be tailored for different applications. The degradation of polyphosphazenes results in the release of phosphate and ammonium ions along with the side groups. [0427]
  • Linear, uncross-linked polymers such as polyphosphazenes can be prepared by thermal ring opening polymerization of (NPCl[0428] 2)3 and the chloro group replaced by amines, alkoxides or organometallic reagents to form hydrolytically stable, high molecular weight poly(organophosphazenes). Depending on the properties of the side groups, the polyphosphazenes can be hydrophobic, hydrophilic or amphiphilic. The polymers can be fabricated into films, membranes and hydrogels for biomedical applications by cross-linking or grafting. Bioerodible polymers for drug delivery devices have been prepared by incorporating hydrolytic side chains of imidazole for skeletal tissue regeneration.
  • Polyphosphazenes are polymers with backbones consisting of nitrogen and phosphorous atoms separated by alternating single and double bonds. Each phosphorous atom is covalently bonded to two side chains. Polyphosphazenes that can be used have a majority of side chains that are acidic and capable of forming salt bridges with di- or trivalent cations. Examples of acidic side chains are carboxylic acid groups and sulfonic acid groups. [0429]
  • Bioerodible polyphosphazenes have at least two differing types of side chains, acidic side groups capable of forming salt bridges with multivalent cations, and side groups that hydrolyze under in vivo conditions, e.g., imidazole groups, amino acid esters, glycerol, and glucosyl. Bioerodible or biodegradable polymers, i.e., polymers that dissolve or degrade within a period that is acceptable in the desired application (usually in vivo therapy), will degrade in less than about five years and most preferably in less than about one year, once exposed to a physiological solution of pH 6-8 having a temperature of between about 25° C. and 38° C. Hydrolysis of the side chain results in erosion of the polymer. Examples of hydrolyzing side chains are unsubstituted and substituted imidizoles and amino acid esters in which the side chain is bonded to the phosphorous atom through an amino linkage. [0430]
  • Methods for synthesis and the analysis of various types of polyphosphazenes are described in U.S. Pat. Nos. 4,440,921, 4,495,174, and 4,880,622, the entire teachings of which are incorporated herein by reference. Methods for the synthesis of the other polymers described above are known to those skilled in the art. See, for example Concise Encyclopedia of Polymer Science and Engineering, J. I. Kroschwitz, editor John Wiley and Sons, New York, N.Y., 1990, the entire teachings of which are incorporated herein by reference. Many polymers, such as poly(acrylic acid), alginates, and PLURONICS™, are commercially available. [0431]
  • Another synthetic hydrogel is poly (vinyl)alcohol (PVA). PVA is not synthesized directly but is the deacetylated product of poly(vinyl acetate). Polyvinyl acetate is usually prepared by radical polymerization of vinyl acetate (bulk, solution or emulsion polymerizations). PVA is formed by either alcoholysis, hydrolysis or aminolysis processes of poly(vinyl acetate). The hydrophilicity and water solubility of PVA can be readily controlled by the extent of hydrolysis and molecular weight. PVA has been widely used as thickening and wetting agent. [0432]
  • PVA gels can be prepared by cross-linking with formaldehyde in the presence of sulfuric acid. These formaldehyde-cross-linked PVA materials have been used as prosthesis for a variety of plastic surgery applications including breast augmentation, diaphragm replacement and bone replacement. However, a variety of complications were found after long term implantation, including calcification of the PVA. [0433]
  • More recently, PVA was made into an insoluble gel using a physical cross-linking process. These gels were prepared with a repeated freezing-thawing process. This causes structural densification of the hydrogel due to the formation of semicrystalline structures. The use of this gel in drug delivery applications has been reported. However, PVA is not truly biodegradable due to the lack of labile bonds within the polymer bond. Only low molecular weight materials are advisable to be used as implant materials. [0434]
  • Another synthetic hydrogel is polyethylene oxide (PEO). PEO can be produced by the anionic or cationic polymerization of ethylene oxide using a variety of initiators. PEO is highly hydrophilic and biocompatible, and has been utilized in a variety of biomedical applications including preparation of biologically relevant conjugates, induction of cell membrane fusion and surface modification of biomaterials. Different polymer architectures have been synthesized and some of their applications in medicine have been recently reviewed. For example, PEO can be made into hydrogels by 7-ray or electron beam irradiation and chemical crosslinking. These hydrogels have been used as matrices for drug delivery and cell adhesion studies. [0435]
  • Pluronic polyols or polyoxamers are block copolymers of PEO and poly(propylene oxide) and are usually synthesized by anionic polymerization in the form of an ABA triblock using a difunctional initiator. Pluronics F 127, which contains 70% ethylene oxide and 30% propylene oxide by weight with an average molecular weight of 11,500, is the most commonly used gel-forming polymer matrix to deliver proteins. [0436]
  • This polymer exhibits a reversible thermal gelation in aqueous solutions at a concentration of 20% or more. Thus, the polymer solution is a liquid at room temperature but gels rapidly in the body. Although the polymer is not degraded by the body, the gels dissolve slowly and the polymer is eventually cleared. This polymer has been utilized in protein delivery and skin burn treatments. [0437]
  • Although PGA is not water soluble, bioerodible hydrogels based on photopolymerized PGA-PEO copolymers have been synthesized and their biological activities investigated. Macromonomers having a poly(ethylene glycol) central block, extended with oligomers of .alpha.-hydroxy acids (e.g., oligo(dl-lactic acid) or oligo(glycolic acid)) and terminated with acrylate groups were synthesized. These hydrogels were designed to form direct contacts with tissues or proteins following photopolymerization, and act as a barrier. [0438]
  • These gels degrade upon hydrolysis of the oligo(α-hydroxy acid) regions into poly(ethylene glycol), the .alpha.-hydroxy acid, and oligo(acrylic acid). The degradation rate of these gels could be tailored from less than 1 day to 4 months by appropriate choice of the oligo(.alpha.-hydroxy acid). The macromonomer could be polymerized using non-toxic photoinitiators with visible light without excess heating or local toxicity. The hydrogels polymerized in contact with tissue adhere tightly to the underlying tissue. In contrast, the gels were nonadhesive if they were polymerized prior to contact with tissue. These hydrogels have been utilized in animal models to prevent post-surgical adhesion and thrombosis of blood vessels and initimal thickening following balloon catheterization. [0439]
  • It can thus be seen that there are a large number of synthetic biodegradable polymers that may be used in the spinal tissue engineering invention described herein. Established polymer chemistries enable one to tailor properties of the synthetic polymers by using different i) functional groups (either on the backbone or side chain), ii) polymer architectures (linear, branched, comb or star), and iii) combinations of polymer species physically mixed (polymer blends or interpenetrating networks) or chemically bonded (copolymers). The current preference for PGA and related polyesters is partially due to their established safety in human applications, and the projected approval of the Food and Drug Administration. PLGA can also be used with specific peptide sequences incorporated into the polymer. Polymers constituted of building blocks similar to components of ECM, e.g., carbohydrates and peptides, may also be used. [0440]
  • Other hydrogels that can be used in the methods of the invention are solidified by either visible or ultraviolet light. These hydrogels are made of macromers including a water soluble region, a biodegradable region, and at least two polymerizable regions as described in U.S. Pat. No. 5,410,016, the entire teachings of which are incorporated herein by reference. For example, the hydrogel can begin with a biodegradable, polymerizable macromer including a core, an extension on each end of the core, and an end cap on each extension. The core is a hydrophilic polymer, the extensions are biodegradable polymers, and the end caps are oligomers capable of cross-linking the macromers upon exposure to visible or ultraviolet light, e.g., long wavelength ultraviolet light. [0441]
  • Examples of such light solidified hydrogels include polyethylene oxide block copolymers, polyethylene glycol polylactic acid copolymers with acrylate end groups, and 10 K polyethylene glycol-glycolide copolymer capped by an acrylate at both ends. As with the PLURONIC™ hydrogels, the copolymers comprising these hydrogels can be manipulated by standard techniques to modify their physical properties such as rate of degradation, differences in crystallinity, and degree of rigidity. [0442]
  • It is known that stem cells are fairly sensitive to temperatures greatly in excess of body temperature. Therefore, in some embodiments of the present invention, the osteobiologic composition is delivered into the disc space at a temperature of between about 37° C. and about 60° C., preferably between about 40° C. and about 50° C., more preferably between about 40° C. and about 45° C. [0443]
  • In some embodiments, a semipermeable membrane is formed around the hydrogel to protect the cells inside. In these instances, the techniques disclosed in U.S. Pat. No. 4,352,883 by Lin, the entire teachings of which are incorporated herein by reference (hereinafter “Lin”), are used. [0444]
  • In one aspect, the instant invention provides a method of encapsulating bone growth cells or growth factors in a semipermeable membrane. The basic approach involves suspending the bone growth cells or growth factors to be encapsulated in a physiologically compatible medium containing a water-soluble substance that can be made insoluble in water, that is, gelled, to provide a temporary protective environment for the tissue. The medium is next formed into droplets containing the bone growth cells or growth factors and gelled, for example, by changing conditions of temperature, pH, or ionic environment. The “temporary capsules” thereby produced are then subjected to a treatment, which can be a known treatment, that results in the production of membranes of a controlled permeability (including impermeability) about the shape-retaining temporary capsules. [0445]
  • The temporary capsules can be fabricated from any nontoxic, water soluble substance that can be gelled to form a shape retaining mass by a change of conditions in the medium in which it is placed, and also may comprise plural groups that are readily ionized to form anionic or cationic groups. The presence of such groups in the polymer enables surface layers of the capsule to be cross-linked to produce a “permanent” membrane when exposed to polymers containing multiple functionalities of the opposite charge. [0446]
  • The presently preferred material for forming the temporary capsules is polysaccharide gums, either natural or synthetic, of the type which can be (a) gelled to form a shape retaining mass by being exposed to a change in conditions such as a pH change or by being exposed to multivalent cations such as Ca[0447] ++; and (b) permanently “crosslinked” or hardened by polymers containing reactive groups such as amine or imine groups which can react with acidic polysaccharide constituents. The presently preferred gum is alkali metal alginate. Other water soluble gums which may be used include guar gum, gum arabic, carrageenan, pectin, tragacanth gum, xanthan gum or acidic fractions thereof. When encapsulating thermally refractory materials, gelatin or agar may be used in place of the gums.
  • The preferred method of formation of the droplets is to force the gum-nutrient-tissue suspension through a vibrating capillary tube placed within the center of the vortex created by rapidly stirring a solution of a multivalent cation. Droplets ejected from the tip of the capillary immediately contact the solution and gel as spheroidal shaped bodies. [0448]
  • The preferred method of forming a permanent semipermeable membrane about the temporary capsules is to “crosslink” surface layers of a gelled gum of the type having free acid groups with polymers containing acid reactive groups such as amine or imine groups. This is typically done in a dilute solution of the selected polymer. Generally, the lower the molecular weight of the polymer, the greater the penetration into the surface of the temporary capsule, and the greater the penetration, the less permeable the resulting membrane. Permanent crosslinks are produced as a consequence of salt formation between the acid reactive groups of the crosslinking polymer and the acid groups of the polysaccharide gum. Within limits, semipermeability can be controlled by setting the molecular weight of the crosslinking polymer, its concentration, and the duration of reaction. Crosslinking polymers which have been used with success include polyethylenimine and polylysine. Molecular weight can vary, depending on the degree of permeability required, between about 3,000 and about 100,000 or more. Good results have been obtained using polymers having an average molecular weight on the order of about 35,000. [0449]
  • The capsules can be engineered to have a selected in vivo useful life by astute selection of the cross-linking polymer. Proteins or polypeptide crosslinkers, e.g., polylysine, are readily attached in vivo resulting in relatively rapid destruction of the membrane. Cross-linkers not readily degradable in mammalian bodies, e.g., polyethyleneimine, result in longer lasting membranes. By selecting the crosslinking polymer or by cross-linking simultaneously or sequentially with two or more such materials, it is possible to preselect the length of time the implanted tissue remains protected. [0450]
  • Optionally, with certain materials used to form the temporary capsules, it is possible to improve mass transfer within the capsule after formation of the permanent membrane by re-establishing the conditions under which the material is liquid, e.g., removing the multivalent cation. This can be done by ion exchange, e.g., immersion in phosphate buffered saline or citrate buffer. In some situations, such as where it is desired to preserve the encapsulated tissue, or where the temporary gelled capsule is permeable, it may be preferable to leave the encapsulated gum in the crosslinked, gelled state. [0451]
  • An alternative method of membrane formation involves an interfacial polycondensation of polyaddition. This approach involves preparing a suspension of temporary capsules in an aqueous solution of the water soluble reactant of a pair of complementary monomers which can form a polymer. Thereafter, the aqueous phase is suspended in a hydrophobic liquid in which the complementary reactant is soluble. When the second reactant is added to the two-phase system, polymerization takes place at the interface. Permeability can be controlled by controlling the makeup of the hydrophobic solvent and the concentration of the reactants. Still another way to form a semipermeable membrane is to include a quantity of protein in the temporary capsule which can thereafter be crosslinked in surface layers by exposure to a solution of a crosslinking agent such as gluteraldehyde. [0452]
  • The foregoing process has been used to encapsulate viable mesenchymal stems cells which, in a medium containing the nutrients and other materials necessary to maintain viability and support in vitro metabolism of the tissue, provide bone growth. [0453]
  • In another aspect, the instant invention provides a tissue implantation method which does not require surgery and which overcomes many of the problems of immune rejection. In accordance with the invention, the capsules are injected into a suitable site in a mammalian body, and function normally until the tissue expires, or until natural body processes succeed in isolating the capsules so that substances required for viability of the tissue are no longer available. At this point, because surgery is not required for the implant, fresh tissue may be readily provided by another injection. The mammalian body may accordingly be provided with the specialized function of the tissue as long as desired. [0454]
  • In a preferred embodiment of the invention, mammalian mesenchymal stems cells are encapsulated in polylysine and polyethyleneimine cross-linked alginate membranes. These may be injected into the polymer matrix of the osteobiologic component. [0455]
  • Accordingly, it is a primary object of the invention to provide a method of encapsulating living a osteogenic component or growth factors within a membrane permeable to the nutrients and other substances needed for maintenance and metabolism and to metabolic products, but impermeable to the polymer matrix material having a molecular weight above a selected level. [0456]
  • Other objects of the invention are to provide a method of implanting living tissue in mammalian bodies and to provide a non-surgical tissue implantation technique. Still another object is to provide a method of encapsulating living tissue which allows the production of capsules having a high surface area to volume ratio and membranes with a preselected in vivo residence time. [0457]
  • Each of IPNs and S-IPNs are extremely desirable because cells can be suspended in the polymer solutions which can be cross-linked by a non-toxic active species, such as by photoinitiation. In some embodiments, both the active species and the initiator are present in an amount that is non-toxic to cells. In other embodiments, the active species is present in an amount that is non-toxic to cells and the initiation occurs via photoinitiation. [0458]
  • Cells can be obtained directed from a donor, from cell culture of cells from a donor, or from established cell culture lines. In the preferred embodiments, cells are obtained directly from a donor, washed and implanted directly in combination with the polymeric material. The cells are cultured using techniques known to those skilled in the art of tissue culture. [0459]
  • Cell attachment and viability can be assessed using scanning electron microscopy, histology, and quantitative assessment with radioisotopes. The function of the implanted cells can be determined using a combination of the above-techniques and functional assays. For example, in the case of hepatocytes, in vivo liver function studies can be performed by placing a cannula into the recipient's common bile duct. Bile can then be collected in increments. Bile pigments can be analyzed by high pressure liquid chromatography looking for underivatized tetrapyrroles or by thin layer chromatography after being converted to azodipyrroles by reaction with diazotized azodipyrroles ethylanthranilate either with or without treatment with P-glucuronidase. Diconjugated and monoconjugated bilirubin can also be determined by thin layer chromatography after alkalinemethanolysis of conjugated bile pigments. In general, as the number of functioning transplanted hepatocytes increases, the levels of conjugated bilirubin will increase. Simple liver function tests can also be done on blood samples, such as albumin production. Analogous organ function studies can be conducted using techniques known to those skilled in the art, as required to determine the extent of cell function after implantation. For example, islet cells of the pancreas may be delivered in a similar fashion to that specifically used to implant hepatocytes, to achieve glucose regulation by appropriate secretion of insulin to cure diabetes. Other endocrine tissues can also be implanted. Studies using labeled glucose as well as studies using protein assays can be performed to quantitate cell mass on the polymer scaffolds. These studies of cell mass can then be correlated with cell functional studies to determine what the appropriate cell mass is. In the case of chondrocytes, function is defined as providing appropriate structural support for the surrounding attached tissues. [0460]
  • This technique can be used to provide multiple cell types, including genetically altered cells, within a three-dimensional scaffolding for the efficient transfer of large number of cells and the promotion of transplant engraftment for the purpose of creating a new tissue or tissue equivalent. It can also be used for immunoprotection of cell transplants while a new tissue or tissue equivalent is growing by excluding the host immune system. [0461]
  • Examples of cells which can be implanted as described herein include chondrocytes and other cells that form cartilage, osteoblasts and other cells that form bone, muscle cells, fibroblasts, and organ cells. As used herein, “organ cells” includes hepatocytes, islet cells, cells of intestinal origin, cells derived from the kidney, and other cells acting primarily to synthesize and secret, or to metabolize materials. [0462]
  • In some embodiments, the osteobiologic component comprises an osteoconductive phase. In some embodiments, the osteoconductive phase comprises a particulate phase comprising a hard tissue, osteoconductive or osteoinductive calcium containing, non-fibrous, powdered compound, wherein the calcium containing compound comprises a material having the formula: [0463]
  • M2+ (10-n)N1+ 2n(ZO4 3-)6 mYx-
  • where n=1-10, and m=2 when x=1, and/or m=1 when x=2 [0464]
  • where M and N are alkali or alkaline earth metals, preferably calcium, magnesium, sodium, zinc and potassium. ZO[0465] 4 is an acid radical, where Z is preferably phosphorus, arsenic, vanadium, sulfur or silicon, or is substituted in whole or part with carbonate (CO3 2-. Y is an anion, preferably halide, hydroxide, or carbonate.
  • Most preferably, the calcium containing compound comprises mono-, di-, octa-, .alpha.-tri-, .beta.-tri-, or tetra-calcium phosphate, hydroxyapatite, fluorapatite, calcium sulfate, calcium fluoride and mixtures thereof. [0466]
  • The calcium containing bone regenerating compound can also contain a bioactive glass comprising metal oxides such as calcium oxide, silicon dioxide, sodium oxide, phosphorus pentoxide, and mixtures thereof, and the like. [0467]
  • Preferably, the calcium containing compound used in the composites of the present invention will have a particle size of about 10 microns to about 1000 microns, and most preferably about 100 microns to about 500 microns. The particles are prepared by conventional processes such as pulverizing, milling, and the like. [0468]
  • In some embodiments, hydroxyapatite particles are preferably the type of dry free-flowing hydroxyapatite particles supplied for use in forming wetted, loose-mass implants, and can be obtained commercially from Orthomatrix Corporation (Dublin, Calif.) or Calcitek (San Diego, Calif.). Particle sizes of between about 250 and 2000 microns are preferred, smaller particles showing increased difficulty in allowing tissue ingrowth and larger particles requiring increased quantities of binder for ease of application. [0469]
  • In some embodiments, the material comprising the osteobiologic component of the present invention has at least one of the following intrinsic properties: [0470]
    More
    Intrinsic Property Preferred Value Preferred Value
    Compression Strength   >1 MPa   >10 MPa
    Fracture Strength   >1 MPa   >10 MPa
    Compression Modulus 0.1-2 GPa 0.2-0.7 GPa
  • In some embodiments, the osteobiologic component of the present invention has the following mechanical performance characteristics: [0471]
    More
    Mechanical Property Preferred Value Preferred Value
    Static Compressive Load >2 kN >4 kN
  • One example of such an osteobiologic composition comprises an in situ formed, porous, polyoxaester scaffold that occupies the space created by the strut described in FIGS. [0472] 2(f) and 2(g).
  • In some embodiments, the polymer has a Tm of no more than about 80° C. This allows the use of water or steam as the heating fluid. In some embodiments, the polymer has a Tm of less than 100° C., and so is less likely to damage surrounding tissue. [0473]
  • In particular, preferred embodiments, in the solidifed form, exhibit mechanical properties approximating those of the cancellous bone. For instance, preferred embodiments of the osetobiologic composition exhibit a load bearing strength of between about 50 and about 200 psi (pounds per square inch), and preferably between about 100 and about 150 psi. Such composites also exhibit a shear stress of between about 10 and 100 psi, and preferably between about 30 and 50 psi, as such units are typically determined in the evaluation of natural tissue and joints. [0474]
  • As used herein, the term “growth factors” encompasses any cellular product that modulates the growth or differentiation of other cells, particularly connective tissue progenitor cells. The growth factors that may be used in accordance with the present invention include, but are not limited to, FGF-1, FGF-2, FGF-4, PDGFs, EGFs, IGFs, PDGF-bb, bone morphogenetic protein-1, bone morphogenetic protein-2, OP-1, transforming growth factor-β, osteoid-inducing factor (OIF), angiogenin(s), endothelins, hepatocyte growth factor and keratinocyte growth factor, osteogenin (bone morphogenetic protein-3); bone morphogenetic protein-2; OP-1; bone morphogenetic protein-2A, -2B, and -7; transforming growth factor-β, HBGF-1 and -2; isoforms of platelet-derived growth factors (PDGF), fibroblast growth factors, epithelial growth factors, isoforms of transforming growth factor-β, insulin-like growth factors, and bone morphogenic proteins, and FGF-1 and 4. [0475]
  • Growth factors which can be used with a matrix of the present invention include, but are not limited to, members of the transforming growth factor-β superfamily, including transforming growth factor-β1,2 and 3, the bone morphogenetic proteins (BMP's), the growth differentiation factors (GDF's), and ADMP-1; members of the fibroblast growth factor family, including acidic and basic fibroblast growth factor (FGF-1 and -2); members of the hedgehog family of proteins, including indian, sonic and desert hedgehog; members of the insulin-like growth factor (IGF) family, including IGF-I and -II; members of the platelet-derived growth factor (PDGF) family, including PDGF-AB, PDGF-BB and PDGF-AA; members of the interleukin (IL) family, including IL-1 thru -6; and members of the colony-stimulating factor (CSF) family, including CSF-1, G-CSF, and GM-CSF. [0476]
  • As noted above, there is a concern that including osteogenic components and osteoinductive components in a heated polymer matrix may render nonviable or denature these components. However, there are some growth factors known to those skilled in the art that are more heat resistant than the majority of growth factors. It is believed that these high temperature growth factors in osteobiologic compositions may be included in osteobiologic compositions that are to be flowed into the disc space at temperatures between body temperature and about 45° C. [0477]
  • Accordingly, in one embodiment, the present invention is a pharmaceutical composition comprising a pharmaceutically acceptable carrier or diluent and (a) at least one polymer flowable between 38° C. and 45° C. selected from the group consisting of homopolymers of poly(ε-caprolactone), poly(p-dioxanone), or poly(trimethylene carbonate) or copolymers or mixtures thereof, or copolyesters of p-dioxanone or trimethylene carbonate and glycolide or lactide or mixtures thereof, and in particular, copolymers of p-dioxanone/glycolide, p-dioxanone/lactide, trimethylene carbonate/glycolide and trimethylene carbonate/lactide, or copolyesters of epsilon.-caprolactone and glycolide or mixtures thereof, or mixtures of homopolymers of ε-caprolactone and lactide, and (b) at least one growth factor resistant to denaturing at at least about 45° C. selected from the group consisting of bone morphogenetic proteins. [0478]
  • As used herein, a “pharmaceutical composition” is a formulation comprising the disclosed compounds and a pharmaceutically acceptable diluent or carrier, in a form suitable for administration to a subject. The quantity of active ingredient (e.g. a growth factor) in a unit dose of composition is an effective amount and may be varied according to the particular treatment involved. As used herein, an “effective amount” of a compound is the quantity which, when administered to a subject in need of treatment, improves the prognosis of the subject, e.g. reduces the severity of one or more of the subject's symptoms associated with a spinal injury. It may be appreciated that it may be necessary to make routine variations to the dosage depending on the age and condition of the patient. The amount of the active ingredient to be administered to a subject will depend on the type of injury and the characteristics of the subject, such as general health, other diseases, age, sex, genotype, body weight and tolerance to drugs. The skilled artisan will be able to determine appropriate dosages depending on these and other factors. [0479]
  • The compounds described herein can be used in pharmaceutical preparations in combination with a pharmaceutically acceptable carrier or diluent. Suitable pharmaceutically acceptable carriers include inert solid fillers or diluents and sterile aqueous or organic solutions. The compounds will be present in such pharmaceutical compositions in amounts sufficient to provide the desired dosage amount in the range described herein. Techniques for formulation and administration of the compounds of the instant invention can be found in [0480] Remington: the Science and Practice of Pharmacy, 19th edition, Mack Publishing Co., Easton, Pa. (1995).
  • Preferably, the matrix material becomes flowable in the temperature range of at least 40° C. and 55° C., more preferably in the temperature range of at least 45° C. and 50° C. [0481]
  • Preferably, the growth factor is resistant to denaturing at a temperature of at least 40° C. In some embodiments, the growth factor is a dimer. In some embodiments, the growth factor is a bone morphogenetic protein dimer. [0482]
  • If desired, substances such as antibiotics, antibacterial agents, and antifungal agents may also be admixed with the polymer. Examples of antimicrobial agents which may be employed include tetracycline, oxytetracycline, chlorotetracycline, neomycin, erithromycin, and its derivative, bacitracin, streptomycin, rifampicin and its derivatives such as N-dimethylrifampicin, kanamycin and chloromycetin. Useful antifungal agents include griseofulvin, mycostatin, miconazole and its derivatives as described in U.S. Pat. No. 3,717,655, the entire teachings of which are incorporated herein by reference; bisdiguanides such as chlorhexidine; and more particularly quaternary ammonium compounds such as domiphen bromide, domiphen chloride, domiphen fluoride, benzalkonium chloride, cetyl pyridinium chloride, dequalinium chloride, the cis isomer of 1-(3-chlorallyl)-3,5,7-triaza-1-azoniaadamantane chloride (available commercially from the Dow Chemical Company under the trademark Dowicil 200) and its analogues as described in U.S. Pat. No. 3,228,828, the entire teachings of which are incorporated herein by reference, cetyl trimethyl ammonium bromide as well as benzethonium chloride and methylbenzethonium chloride such as described in U.S. Pat. Nos. 2,170,111, 2,115,250 and 2,229,024, the entire teachings of which are incorporated herein by reference; the carbanilides and salicylanilides such 3,4,4′-trichlorocarbanilide, and 3,4′5-tribromosalicylanilide; the hydroxydiphenyls such as dichlorophene, tetrachlorophene, hexachlorophene, and 2,4,4′-trichloro-2′-hydroxydiphenylether; and organometallic and halogen antiseptics such as sinc pyrithione, silver sulfadiazone, silver uracil, iodine, and the iodophores derived from non-ionic surface active agents such as are described in U.S. Pat. Nos. 2,710,277 and 2,977,315, the entire teachings of which are incorporated herein by reference, and from polyvinylpyrrolidone such as described in U.S. Pat. Nos. 2,706,701, 2,826,532 and 2,900,305, the entire teachings of which are incorporated herein by reference. [0483]
  • Optionally, the matrix has antibodies that have affinity for connective tissue progenitor stem cells bound to the surface thereof. Suitable antibodies, include by way of example, STRO-1, SH-2, SH-3, SH-4, SB-10, SB-20, and antibodies to alkaline phosphatase. Such antibodies are described in Haynesworth et al., [0484] Bone (1992), 13:69-80; Bruder, S. et al., Trans Ortho Res Soc (1996), 21:574; Haynesworth, S. E., et al., Bone (1992), 13:69-80; Stewart, K., et al, J Bone Miner Res (1996), 11(Suppl.):S142; Flemming J E, et al., in “Embryonic Human Skin. Developmental Dynamics,” 212:119-132, (1998); and Bruder S P, et al., Bone (1997), 21(3): 225-235, the entire teachings of which are incorporated herein by reference.
  • In U.S. Pat. No. 6,197,325, the entire teachings of which are incorporated herein by reference, Mac Phee discloses that drugs, polyclonal and monoclonal antibodies and other compounds, including, but not limited to, DBM and bone morphogenetic proteins may be added to the matrix, such as a matrix of the present invention. They accelerate wound healing, combat infection, neoplasia, and/or other disease processes, mediate or enhance the activity of the growth factor in the matrix, and/or interfere with matrix components which inhibit the activities of the growth factor in the matrix. These drugs may include, but are not limited to: antibiotics, such as tetracycline and ciprofloxacin; antiproliferative/cytotoxic drugs, such as 5-fluorouracil (5-FU), taxol and/or taxotere; antivirals, such as gangcyclovir, zidovudine, amantidine, vidarabine, ribaravin, trifluridine, acyclovir, dideoxyuridine and antibodies to viral components or gene products; cytokines, such as α- or β- or γ-Interferon, α- or β-tumor necrosis factor, and interleukins; colony stimulating factors; erythropoietin; antifungals, such as diflucan, ketaconizole and nystatin; antiparasitic agents, such as pentamidine; anti-inflammatory agents, such as α-1-anti-trypsin and α-1-antichymotrypsin; steroids; anesthetics; analgesics; and hormones. Other compounds which may be added to the matrix include, but are not limited to: vitamins and other nutritional supplements; hormones; glycoproteins; fibronectin; peptides and proteins; carbohydrates (both simple and/or complex); proteoglycans; antiangiogenins; antigens; oligonucleotides (sense and/or antisense DNA and/or RNA); bone morphogenetic proteins; DBM; antibodies (for example, to infectious agents, tumors, drugs or hormones); and gene therapy reagents. Genetically altered cells and/or other cells may also be included in the matrix of this invention. [0485]
  • If desired, substances such as pain killers and narcotics may also be admixed with the polymer for delivery and release to the disc space. [0486]
  • In some embodiments of the resent invention, the additive is embedded within the matrix material of the scaffold. In other embodiments, the additive resides on the inner surface of the open porosity created by the leaching of the leachate. In other embodiments, the additive resides within the hydrogel phase. [0487]
  • When the osteobiologic composition comprises one or more bone morphogenetic proteins, they are preferably located on the inner surface of the open porosity in the case where the scaffold is formed prior to being populated with cells, and are preferably located within the hydrogel phase in the case where a hydrogel is used to deliver cells at the same time the scaffold is delivered. This is done so that the cells will contact the bone morphogenetic proteins as soon as possible following implantation in order to initiate the bone forming process. Furthermore, since the bone morphogenetic proteins have a limited time in which they are active in inducing cells to form bone, it is important to expose the cells to the bone morphogenetic proteins as soon as possible to take maximum advantage of their potency. [0488]
  • When osteoprogenitor cells are seeded onto the scaffold following in situ formation of the scaffold, they preferably adhere to the surface of the inner porosity of the scaffold. This is important because osteoprogenitor cells must attach to a substrate in order to begin forming bone. Likewise when osteoprogenitor cells are delivered to the fusion site while encapsulated in a hydrogel, they preferably attach to the inner porosity of the hydrogel. [0489]
  • In some embodiments, bone morphogenetic protein is present in the scaffold in a concentration of at least 2 times the atologus concentration. More preferably, the bone morphogenetic protein is present in the scaffold in a concentration of at least 100 times the autologous concentration. [0490]
  • In some embodiments, mesenchymnal stem cells are present in the scaffold in a concentration of at least 2 times the autologous concentration. More preferably the mesenchymnal stem cells are present in the scaffolding in a concentration of 10 times the autologous concentration, and most preferably they are present in a concentration of 100 times the autologous concentration. [0491]
  • In some embodiments, the osteobiologic composition has a sufficiently high osteobiologic nature and a matrix that is sufficiently resistant to degradation that the bone growth essentially fills the entire porosity of the scaffold of the osteobiologic composition before there is any significant degradation of the matrix. In such a case, the new bone can begin to significiantly share the compressive load experienced by the device before the device undergoes a significant loss in strength. [0492]
  • In preferred embodiments, bony ingrowth penetrates at least 50% of the distance to the center of the implant before the matrix loses 50% of its weight. In more preferred embodiments, bony ingrowth penetrates at least 75% of the distance to the center of the implant before the matrix loses 25% of its weight. In more preferred embodiments, bony ingrowth penetrates at least 90% of the distance to the center of the implant before the matrix loses 10% of its weight. [0493]
  • In preferred embodiments, bony ingrowth penetrates at least 50% of the distance to the center of the implant before the matrix loses 50% of its compressive strength. In more preferred embodiments, bony ingrowth penetrates at least 75% of the distance to the center of the implant before the matrix loses 25% of its compressive strength. In more preferred embodiments, bony ingrowth penetrates at least 90% of the distance to the center of the implant before the matrix loses 10% of its compressive strength. [0494]
  • In accord with the present invention, the injectable implants of the invention can be used to fuse facets and to fuse the interspinous region. In some embodiments, the implants of the present invention use an elastomer to tension the interspinous region to correct lordotic angle. [0495]
  • It is further believed that the above noted osteobiologic compositions can be advantageously used in vertebroplasty procedures, particularly when delivered into the porosity of a skeleton created in the vertebral body, as disclosed in U.S. patent application by Martin Reynolds entitled “Method of Performing Embolism Free Vertebroplasty and Devise Therefore,” which was filed on Nov. 21, 2002, the entire teachings of which are incorporated herein by reference. [0496]
  • Additional Embodiments [0497]
  • In one embodiment, the present invention is an intervertebral fusion device for providing bony fusion across a disc space. The device comprises a strut. The strut includes an upper surface for bearing against the upper endplate, a lower surface for bearing against the lower endplate, and an in-situ formed load bearing composition disposed between the upper and lower surfaces. [0498]
  • In another embodiment, the present invention is an intervertebral fusion device comprising a strut, having a shape memory, and an in-situ formed osteobiologic component. The strut further includes (i) an upper surface for bearing against the upper endplate and (ii) a lower surface for bearing against the lower endplate. [0499]
  • In another embodiment, the rpesent invention is an intervertebral fusion device comprising a strut and an in-situ formed osteobiologic component. The strut includes an upper surface for bearing against the upper endplate, and a lower surface for bearing against the lower endplate. The in-situ formed osteobiologic component includes a matrix component having an internal surface defining a scaffold having open porosity suitable for bone growth therethrough, and an osteogenic component located within the open porosity. [0500]
  • In another embodiment, the present invention is an intervertebral fusion device comprising a strut and an in-situ formed osteobiologic component. The strut includes an upper surface for bearing against the upper endplate, and a lower surface for bearing against the lower endplate. The in-situ formed osteobiologic component includes an injectable matrix component, and an osteoinductive component embedded within the matrix. [0501]
  • In another embodiment, the present invention is an intervertebral fusion device comprising a strut and an in-situ formed osteobiologic component. The strut includes an upper surface for bearing against the upper endplate, and a lower surface for bearing against the lower endplate. The in-situ formed osteobiologic component includes an injectable matrix component, and a porogen embedded within the matrix. [0502]
  • In another embodiment, the present invention is an intervertebral fusion device comprising a strut and an in-situ formed osteobiologic component. The strut includes an upper surface for bearing against the upper endplate, and a lower surface for bearing against the lower endplate. The in-situ formed osteobiologic component includes an expandable device defining a cavity, and an injectable osteobiologic composition located within the cavity. [0503]
  • In another embodiment, the present invention is an intervertebral fusion device comprising a strut that includes an expandable device having a cavity, an upper surface for bearing against the upper endplate, a lower surface for bearing against the lower endplate, and an inner wall defining a through hole. The strut further includes an injectable load bearing composition located within the cavity. The fusuion device further includes an osteobiologic component located in the throughhole. [0504]
  • In another embodiment, the present invention is an intervertebral fusion device comprising a strut and an in-situ formed osteobiologic component. The strut includes an upper surface for bearing against the upper endplate a lower surface for bearing against the lower endplate. Preferably, the in-situ formed osteobiologic component includes an injectable, matrix component essentially free of monomer. [0505]
  • In another embodiment, the present invention is an intervertebral fusion device for providing bony fusion across a disc space, comprising a strut. The strut includes an upper surface for bearing against the upper endplate, a lower surface for bearing against the lower endplate, and an in-situ formed load bearing composition disposed between the upper and lower surfaces and made of a material comprising a cross-linked resorbable polymer. [0506]
  • The Preferred Embodiments [0507]
  • As used herein, the term “toroid” refers to a surface obtained by at least partially rotating a closed curve, which lies in a plane, about an axis parallel to the plane and which does not intersect the curve. An example of an “open cavity defined by an outer surface of a toroid” is a hole. [0508]
  • In one preferred embodiment, the present invention is an intervertebral spinal fusion device comprising at least one arcuate inflatable balloon that upon expansion between two adjacent vertebrae at least partially restores natural a natural angle between two adjacent vertebrae, said device having a footprint that substantially corresponds to a perimeter of a vertebral endplate. [0509]
  • Preferably, the intervertebral spinal fusion device has an upper area, a lower area, an anterior area and a posterior area. Upon inflation, said device can have a footprint that substantially corresponds to a rim of a vertebral endplate and said anterior area height being greater than said posterior area height. More preferably, upon expansion, at least a portion of the device has a generally toroidal shape thereby defining an open cavity having an axial dimension and a radial dimension. In one embodiment, the device comprises at least one exandable balloon that contains a plurality of lumena. [0510]
  • In a particularly preferred embodiment, the device comprises at least one said balloon including a resorbable, semi-permeable material selected from the group consisting of polyolefin copolymers, polyethylene, polycarbonate, polyethylene terephthalate, ether-ketone polymers, woven fibers, nonwoven fibers, fabrics and metal mesh. [0511]
  • In a preferred embodiment, the balloon defines at least one opening. [0512]
  • In another embodimemt, the upper and lower areas of the device have a plurality of outward projections. The outward projections preferably include polyetherether ketone (PEEK). [0513]
  • The upper area of the device can include at least one material selected from the group consisting of polyether block copolymer (PEBAX), ABS (acrylonitrile butadiene styrene), ANS (acrylonitrile styrene), delrin acetal; PVC (polyvinyl chloride), PEN (polyethylene napthalate), PBT (polybutylene terephthalate), polycarbonate, PEI (polyetherimide), PES (polyether sulfone), PET (polyethylene terephthalate), PETG (polyethylene terephthalate glycol), polyamide, aromatic polyamide, polyether, polyester, polymethylmethacrylate, polyurethane copolymer, ethylene vinyl acetate (EVA), ethylene vinyl alcohol, polyethylene, latex rubber, FEP (fluorinated ethylene polymer), .PTFE (polytetrafluoroethylene), PFA (perfluoro-alkoxyalkane), polypropylene, polyolefin, polysiloxane, liquid crystal polymer, ionomer, poly(ethylene-co-methacrylic) acid, silicone rubber, SAN (styrene acrylonitrile), nylon, polyether block amide and thermoplastic elastomer. [0514]
  • In one preferred embodiment, the device of the present invention has at least one balloon that contains at least one member of the group consisting of a load-bearing component and an osteobiologic component. The load-bearing and the osteobiologic components can be used alone or in combination. Combination is preferred. In a particularly preferred embodiment, the load-bearing and the osteobiological components are resorbable. [0515]
  • The the load-bearing component can comprise at least one compound selected from the group consisting of poly(lactic acid), poly(glycolic acid), p-dioxanone fibers, polyarylethyl, polymethylmethacrylate, polyurethane, amino-acid-derived polycarbonate, polycaprolactone, aliphatic polyesters, calcium phosphate, unsaturated linear polyesters, vinyl pyrrolidone and polypropylene fumarate diacrylate, or mixtures thereof. [0516]
  • The osteobiologic component can include at least one element selected from the group consisting of mesenchymal stem cells, growth factors, cancellous bone chips hydroxyapatite, tri-calcium phosphate, polylactic acid, polyglycolic acid, polygalactic acid, polycaprolactone, polyethylene oxide, polypropylene oxide, polysulfone, polyethylene, polypropylene, hyaluronic acid, bioglass, gelatin, collagen and chopped polymeric fibers or mixtures thereof. [0517]
  • As used herein, the term “cancellous” refers to a bone having a porous structure. The normal type of adult mammalian bone, whether cancellous or compact, is composed of parallel lamellae in the former and concentric lamellae in the latter; lamellar organization reflects a repeating pattern of collagen fibroarchitecture. Adult bone consisting of mineralised regularly ordered parallel collagen fibres more loosely organised than the lamellar bone of the shaft of adult long bones, such as bone found in the end of long bones, is known as “cancellous bone”. [0518]
  • In another preferred embodiment, the device can further comprise an osteoinductive component and an osteoconductive component. [0519]
  • The osteoinductive component can include at least one compound selected from the group consisting of fibroblast growth factors, such as (FGFs) FGF-1, FGF-2 and FGF-4; platelet-derived growth factors (PDGFs), such as PDGF-AB, PDGF-BB, PDGF-AA; epithelial growth factors EGFs; insulin-like growth factors (IGF), such as IGF-I, IGF-II; osteogenic protein-I (OP-1); transforming growth factors (TGFs), such as transforming growth factor-β, transforming growth factor-β1, transforming growth factor-β2, transforming growth factor-β3; osteoid-inducing factor (OIF); angiogenin(s); endothelins; hepatocyte growth factor and keratinocyte growth factor; bone morphogenetic proteins (BMPs), such as osteogenin (bone morphogenetic protein-3), bone morphogenetic protein-2; bone morphogenetic protein-2A, bone morphogenetic protein-2B, bone morphogenetic protein-7; heparin-binding growth factors (HBGFs), such as HBGF-1, HBGF-2; isoforms of platelet-derived growth factors, fibroblast growth factors, epithelial growth factors transforming growth factor-β, insulin-like growth factors, bone morphogenic proteins, the bone morphogenetic proteins and the growth differentiation factors (GDF's); Indian hedgehog, sonic hedgehog, desert hedgehog; cytokines, such as IL-1, IL-2, IL-3, IL-4, IL-5, IL-6; colony-stimulating factors (CSFs), such as CSF-1, G-CSF and GM-CSF or mixtures thereof. [0520]
  • The osteoconductive component can include at least one compound selected from the group consisting of a material having the formula: [0521]
  • M2+ (10-n)N1+ 2n(ZO4 3-)6 mYx
  • where [0522]
  • n=1-10, and m=2 when x=1, and/or m=1 when x=2; [0523]
  • M and N are alkali or alkaline earth metals; [0524]
  • ZO[0525] 4 is an acid radical, where Z is phosphorus, arsenic, vanadium, sulfur or silicon; and
  • Y is an anion, preferably halide, hydroxide, or carbonate. [0526]
  • The osteoconductive component can further include at least one of material selected from the group consisting of mono-calcium phosphate, di-calcium phosphate, octa-calcium phosphate, alpha-tri-calcium phosphate, beta-tri-calcium phosphate, or tetra-calcium phosphate, hydroxyapatite, fluorapatite, calcium sulfate, calcium fluoride, calcium oxide, silicon dioxide, sodium oxide, and phosphorus pentoxide or mixtures thereof. [0527]
  • In another preferred embodiment, the osteobiologic component can further include at least one water-soluble materials selected from the group consisting of gelatin, salts, polysaccharides and proteins. [0528]
  • A particularly preferred embodiment of the present invention is an intervertebral spinal fusion device shown in FIGS. [0529] 17(a) (collapsed) and (b) (expanded). The device 100 comprises (a) a partially rigid anterior frame 110 detachably connected to a first fluid communication means 120, said frame having an upper inflatable rim 130 and a lower inflatable rim 140; and (b) a rigid posterior expandable frame 150, detachably connected to a second fluid communication means 122, said frame having a rigid upper rim 160 and a rigid lower rim 170, connected respectively to the upper inflatable rim 130 and lower inflatable rim 140 of the anterior frame 110.
  • Preferably, the device further comprises at least one [0530] mesh element 180 connected to the upper and the lower inflatable rims 130 and 140 of the anterior frame 110. At least one of the upper and the lower inflatable rims 130 and 140 of the anterior frame 110 of the device 100 can have a plurality of outward projections 190.
  • Most preferably, the [0531] posterior frame 150 of the device further includes at least one telescopically expandable supporting element 200, each said supporting element being connected to the upper and the lower rigid rims 160 and 170 of the posterior frame 150.
  • [0532] Device 100 can be inserted into an intervertebral space in a collapsed state 210. Device 100 can next be oriented so that the anterior frame 110 of the device is oriented to face an anterior aspect of a vertebra, the posterior frame 150 of the device is oriented to face a posterior aspect of the vertebra and the upper and lower rims 130, 140, 160 and 170 of each frame face upper and lower vertebral endplates endplates, respectively.
  • In a preferred embodiment, at least one of the load-bearing component and the osteobiologic component is directed into the device by directing at least one component under pressure through at least one of the first and the second fluid communication means [0533] 120 and 122, thereby causing the device to expand and directing the upper inflatable rim 130 and the lower inflatable rim 140 of the anterior frame and a posterior frame 150 of the device against the respective vertebral endplates, thereby at least partially restoring a natural angle between two adjacent vertebrae.
  • In a particularly preferred embodiment, upon at least partially filling the upper and lower [0534] inflatable rims 130 and 140 and the posterior frame 150 between two adjacent vertebrae (not shown), natural angle between said two vertebrae is at least partially restored. Preferably, upon filling the upper and the lower inflatable rims 130 and 140 and the posterior frame 150, the distance D between the upper and the lower inflatable rims is different from the height h of the posterior frame. In one embodiment, upon at least partially filling the upper and the lower inflatable rims 130 and 140, said rims each have a footprint substantially corresponding to a rim of a vertebral endplate. Preferably, upon at least partially filling the upper and the lower inflatable rims 130 and 140 and the posterior frame 150, the device defines an open cavity 205 having an axial and a radial dimensions.
  • In another preferred embodiment, the present invention is a method of making an intervertebral spinal fusion device comprising (a) inserting an inflatable device through a cannula into an intervertebral space; (b) orienting said inflatable device so that upon expansion a natural angle between two adjacent vertebrae will be at least partially restored; and (c) directing at least one member of the group consisting of a load-bearing component and an osteobiologic component into the inflatable device through the fluid communication means. Most preferably the method of the present invention further includes the step of hardening the load-bearing component. In one embodiment, said inflatable device includes an arcuate balloon connected to at least one fluid communication means, wherein said inflatable device upon expansion between two adjacent vertebrae has a footprint that substantially corresponds to a perimeter of a vertebral endplate and at least partially restores a natural angle between two adjacent vertebrae. In another embodiment, said inflatable device includes at least one inflatable balloon, said device having an upper area, a lower area, an anterior area and a posterior area, and where upon expansion of the upper and the lower areas against the respective vertebral endplates, said anterior area is unequal to than said posterior area height, and a footprint of the device substantially corresponds to a rim of a vertebral endplate. The at least one balloon can contain a plurality of lumena. [0535]
  • Preferably, the anterior area of the inflatable device is oriented to face an anterior aspect of a vertebra and the posterior area of the device is oriented to face a posterior aspect of the vertebra. [0536]
  • Most preferably, at least one of the load-bearing component and the osteobiologic component is directed into the balloon by directing at least one component under pressure through the fluid communication means, thereby causing the balloon to expand and directing the upper area and the lower area of the device against the respective vertebral endplates, thereby at least partially restoring a natural angle between two adjacent vertebrae. [0537]
  • In another preferred embodiment, at least a portion of the device used to practice the method of the present invention, upon expansion, has a generally toroidal shape thereby forming an open cavity defined by an outer surface of the toroidal shape having an axial dimension and a radial dimension. Preferably, the at least a portion of the device is oriented so that the axial dimension of the open cavity is substantially parallel to a major axis of a spinal column of a patient in which the device has been implanted. [0538]
  • In one embodiment, at least one of a load-bearing component and an osteobiologic component can be directed into the open cavity defined by the expanded device. [0539]
  • The method of the present invention can further include the step of dissolving at least one water-soluble material, thereby forming a porous matrix. [0540]
  • Preferably, the method of the present invention further includes the step of directing into the inflatable device osteoinductive and/or osteoconductive components. [0541]
  • In one preferred embodiment, the present invention is a method of at least partially restoring a natural angle between two adjacent vertebrae comprising: (a) inserting an inflatable device through a cannula into an intervertebral space; (b) orienting said inflatable device so that upon expansion a natural angle between two adjacent vertebrae will be at least partially restored; and (c) expanding said inflatable device by directing at least one of a load-bearing component and an osteobiologic component, into said inflatable device. The inflatable devices suitable for practicing the method of the present invention are described above. [0542]
  • Preferably, the method of the present invention includes the step of inflating said inflatable device. Inflating includes introducing at least one of a load-bearing component and an osteobiologic component into said device by directing at least one component through the fluid communication means, thereby allowing the lower area and the upper area to engage the respective endplates and the anterior area height of said inflatable device to be greater than the posterior area height, thereby at least partially restoring or creating a natural angle between two adjacent vertebrae. Most preferably, the method further includes the step of hardening at least one of the load-bearing component and an osteobiologic component. [0543]
  • In a preferred embodiment, the device upon expansion has a generally toroidal shape thereby forming an open cavity defined by an outer surface of the toroidal shape and having an axial dimension and a radial dimension and the step of orienting said inflatable device includes orienting at least a portion of the device so that so that the axial dimension of the open cavity is substantially parallel to a major axis of a spinal column of a patient in which the device has been implanted. In one embodiment, the method further includes the step of introducing at least one of the load-bearing component and the osteobiologic component into the cavity and the step of hardening at least one of the load-bearing component and an osteobiologic component. The method can further includes the step of dissolving at least one water-soluble material, thereby forming a porous matrix. [0544]
  • The invention will now be further and secificaly described by the following examples that are nopt intended to be limiting in any way. [0545]
  • EXEMPLIFICATION Example 1 Employing a Method of the Present Invention
  • In performing a preferred method of the present invention, the patient is brought to the pre-surgical area and prepped. Anesthesia is then induced and the area of the spine is further prepped. A small incision through the muscles is opened under dissecting microscopic visualization. The incision is made as small as possible and is longitudinal in the plane of the spine. The paravertebral muscles are separated by blunt dissection and held apart with forceps and dividers. The intervertebral disc area is visualized, with initial exposure down to the lamina. The area below the lamina, at the point of the intervertebral foramina, can also be exposed. [0546]
  • The disc is examined for extruded material and any extruded material is removed. Magnetic resonance imaging (“MRI”) data can be used to determine the integrity of the annulus fibrosis at this point. An arthroscope is inserted into the disc and used to examine the inside of the annulus. Optionally, an intraoperative discogram can be performed, in which a dye material is inserted and visualized in order to substantiate the integrity of the annulus fibrosis. Points of weakness, or rents, in the annulus fibrosis are identified and located and suitable means, e.g., a bioabsorbable glue is employed to block these rents. If balloons are used to deliver all of the flowable materials used in the present invention, then the rents need not be patched. [0547]
  • Distraction of the intervertebral disc space can then be accomplished, as described above, by inserting a deflated balloon into the disc space and delivering a fluid (preferably, the flowable load bearing component of the present invention) into the balloon cavity. [0548]
  • Next, the endplates of the opposing vertebral body are partially decorticated, typically through the use of a curette, in order to allow blood flow into the disc space. [0549]
  • After endplate decortication, the application cannula is inserted into the joint or disc space and under visualization from the fiberoptic scope the biomaterial is delivered. The flow of the biomaterial is controlled by the operator via a foot pedal connected to the pumping mechanism on the polymer canister. The biomaterial flows from the tip of the application catheter to fill the space provided. [0550]
  • If the load bearing component has a flowable component, the flowable component is preferably solidified within 3 to 5 minutes, and preferably within 1 to 2 minutes. Once the disc space is suitably distracted, the osteobiologic component of the present invention is introduced to the distracted space, thereby filling the remainder of the disc space. The arthroscopic cannula and the application cannula are removed. The flowable materials are further allowed to harden over 15 to 20 minutes. [0551]
  • The delivered biomaterial is allowed to cure, or cured by minimally invasive means and in such a manner that the cured biomaterial is retained in apposition to the prepared site. As described herein, the biomaterial can be cured by any suitable means, either in a single step or in stages as it is delivered. Once cured, the biomaterial surface can be contoured as needed by other suitable, e.g., endoscopic or arthroscopic, instruments. The joint is irrigated and the instruments removed from the portals. [0552]
  • At that point, interoperative x-rays are obtained to substantiate the preservation of the intervertebral disc space. Direct observation of the intervertebral foramina for free cursing of the nerve rootlet is substantiated by visualization. The retracted muscles are replaced and the local fascia is closed with interrupted absorbable suture. The subcutaneous fascia and skin are then closed in the usual fashion. The wound is then dressed. [0553]
  • Example 2 A Surgical Procedure that Employs Methods and Devices of the Present Invention
  • A surgical procedure to fuse the vertebrae using methods and devices of the present invention can comprise the following steps: [0554]
  • i. Puncture or cut a flap in the annulus fibrosus and insert a small diameter tube into the slit, [0555]
  • ii. Perform a conventional discectomy to remove the nucleus pulposus, [0556]
  • iii. Insert a small diameter tube, e.g. a cannula, into the disc space through the slit, [0557]
  • iv. Insert a strut, e.g. a balloon or a ramp having a partially annular shape, into the disc space through the tube, [0558]
  • v. Flow glucose-containing polycaprolactone into the disc space including the volume defined by the outer surface of the partially annular balloon or a ramp, through the tube at about 70° C. Upon cooling to 37° C., the polycaprolactone should become solid, thereby supplementing the mechanical attributes of the strut, [0559]
  • vi. Leach out the glucose, therby forming a porous matrix. [0560]
  • vii. Flow solutions laden with osteobiologic materials through the porous matrix, so that the osteobiologic materials collect in the pores. The tube can also have a vacuum port to collect the eluted solution. [0561]
  • viii. remove the tube(s), seal the flap, and wait a month for bone growth. [0562]
  • The result of this procedure is a formation of a fusion cage. This procedure has numerous advantages. First, the resulting cage fills and supports the entire disc space, and so it is stable and is not prone to subsidence. Second, the minimally invasive treatment of the annulus fiborsus allows the resulting cage to be held in place by the retained annulus fibrosus. Third, the in situ formation of a scaffold eliminates the need in high impaction forces. Four, by the very nature of an inflatable device, it is adjusted to fit the desired disc height. [0563]
  • Example 3 Harvesting Progenitor Cells for Use in Osteobiologic Material
  • Prior to performing spinal surgery, approximately 5 cc of bone marrow is aspirated from the iliac crest of the patient into a heparinized syringe tube. The heparinized marrow is then passed through a selective cell attachment filter. The filter is designed for selective attachment of osteoprogenitor cells such as mesenchymal stem cells and osteoblasts. Following selective cell attachment, the cells are tripsinized off of the filter and collected in a flask. The flask is then centrifuged to precipitate a cell pellet on the bottom of the flask and the supernatant is poured off. The cells are then mixed with the injectable precursor form of the hydrogel. The precursor hydrogel is then poured into molds that are between 50-250 um in any dimension. The precursor hydrogel is then cured, for example with a photoinitiator, to yield cell loaded hydrogel particles. These cell-hydrogel particles are then mixed with the viscous form of the hardenable material and injected as the osteobiologic composition. [0564]
  • Example 4 Desirable Specifications for Lumbar Fusion Device
  • Specifications for lumbar interbody fusion devices are often formulated assuming the following characteristics: [0565]
  • a) each vertebral endplate of a patient has a 1500 mm cross-sectional area, [0566]
  • b) the maximum in vivo load experienced by a patient is 3.4 kN; [0567]
  • c) the ultimate strength of a vertebral body is about 8.2 kN; [0568]
  • d) the device should initially be able resist the maximum in vivo load; [0569]
  • e) after one year, the device should be able to resist half the maximum in vivo load, [0570]
  • f) the strut portion of the device will have a footprint of 20 areal % of the disc space. [0571]
  • Accordingly, the following criteria for the device can be obtained: [0572]
  • Strength of a Load-Bearing Component [0573] Ultimate Strength = 8.2 kN 300 mm 2 = 27 MPa ( 1 ) Max in Vivo Load = 3.4 kN 300 mm 2 = 11.3 MPa ( 2 )
    Figure US20040230309A1-20041118-M00001
  • Because both the strut and osteobiologic components will initially share the axial compressive load of the spine, the initial minimum strength required by the device may be decreased. If the OB composition is chosen to provide a 5 MPa strength and a 0.05 GPa modulus for at least 6-12 weeks in order to mimic cancellous bone, then the OB composition may share about 10% of the applied compressive load when the modulus of the strut is 2 GPa (assuming no annulus fibrosis). Therefore, the strength of the strut may be about 10% lower. [0574]
  • Modulus of a Load-Bearing Component [0575]
  • It is preferred that the devices of the present invention have a stiffness of at least 0.5 kN/mm. This lower preferred limit corresponds to the stiffness of conventional allograft cages. However, it is believed by some that the low stiffness of the allograft cages may sometime cause too much microfracture in the remodeling process. Therefore, in some embodiments, the stiffness of the devices of the present invention is preferably at least 5 kN/mm. Because it is believed that excessive device stiffness may undesirably cause stress shielding of the osteobiologic composition (and bone resorption), the stiffness of the device of the present invention is desirably no more than 50 kN/mm. [0576]
  • In many embodiments of the present invention, the stiffness of the device of the present invention is between 10 and 20 kN/mm. This range of values is comfortably between the range of stiffnesses found in conventional allograft cages (0.6-2.6 kN/mm) and CFRP cages (20-30 kN/mm). Accordingly, it is believed that the devices of the present invention will have stiffness appropriate for the support of bony fusion through the disc space. [0577]
  • By way of non-limiting explanation, the stiffness of a component can be calculated as follows: [0578]
  • Comp.Modulus (GPa)×Area(mm 2)/Disc Space Depth (mm)=Stiffness (kN/mm)  (7).
  • Assuming a disc space depth of 10 mm and area of 300 mm[0579] 2, the following table can be constructed:
    TABLE I
    Intrinsic Material Device
    Compressive Modulus (GPa) Stiffness (kN/mm)
    0.1 3
    0.5 15
    1.0 30
    1.5 45
  • Because both the strut and osteobiologic components will initially share the axial compressive load of the spine, the initial minimum modulus required by the device may be decreased. If the OB composition is chosen to provide a 5 MPa strength and a 0.05 GPa modulus for at least 6-12 weeks in order to mimic cancellous bone, then the OB composition may share about 10% of the applied compressive load when the modulus of the strut is 2 GPa (assuming no annulus fibrosis). Therefore, the modulus of the strut may be about 10% lower. [0580]
  • Similarly, if an initial device stiffness of 15 kN/mm is desired, then the strut stiffness should be about 1 GPa. As noted above, the material reported by Timmer meets this requirement. [0581]
  • Example 5 Combinations of Materials and Devices
  • By way of introduction, the compositions and materials suitable for use in the present invention will be described below. [0582]
  • Exemplary compositions suitable for use as load-bearing component of the present invention that include a fumarate-based polymer (such as polypropylene fumarate) cross-linked with a cross-linking agent containing a polypropylene fumarate-unit, such as polypropylene fumarate-diacrylate are disclosed in Timmer, [0583] Biomaterials (2003) 24:571-577 (hereinafter, “Timmer”), the entire teachings of which are incorporated herein by reference. These compositions are characterized by a high initial compressive strength (about 10-30 MPa) that typically increases over the first 12 weeks, high resistance to hydrolytic degradation (about 20-50 at 52 weeks), and an acceptable modulus for use as a strut (0.5-1.2 GPa).
  • Exemplary compositions suitable for use as resorbable cross-linkable component comprises those cross-linkable components disclosed by Wise in U.S. Pat. No. 6,071,982 (hereinafter, “Wise”), the entire teaching of which are herein incorporated by reference. [0584]
  • Exemplary absorbable elastomeric materials that allows resorbale devices to be delivered through the cannula are disclosed in U.S. Pat. No. 6,113,624 by Bezwada (hereinafter, “Bezwada), the entire teachings of which are incorporated herein by reference. [0585]
  • Exemplary injectable osteobiologic polymer-based compositions suitable for use in the present invention are described in the U.S. Pat. No. 5,679,723 by Cooper (herein after, “Cooper”), the entire teachings of which are incorporated herein by reference. [0586]
  • Exemplary osteobiologic compositions in which porosity is produced in situ, are described in the U.S. Pat. No. 5,522,895 by Mikos (hereinafter, “Mikos”), the entire teachings of which are incorporated herein by reference. [0587]
  • As used herein, “PCL” is polycaprolactone, “PLA” is poly(lactic acid), “PPF” is polypropylene fumarate and “PMMA” is polymethylmethacrylate. [0588]
  • As used herein, “IPN” or “interpenetrating networks” is a composition comprising two cross-linkable polymers, wherein two cross-linkable polymers, upon exposure to appropriate cross-linking agents, cross-links with itself, but not with the other cross-linked polymer. “S-IPN” or “Semi-interpenetrating networks” is a composition comprising a first cross-linkable polymer and a second non-cross-linkable polymer whrein, upon exposure to an appropriate cross-linking agent, the first cross-linkable polymer cross-links with itself, while the second polymer remains unaffected. [0589]
  • According to Hao, [0590] Biomaterials (2003), 24:1531-39, (hereinafter, “Hao”) the entire teachings of which are incorporated herein by reference, certain mechanical properties of polycaprolactone increased by about 3 fold when it was formed as a S-IPN. When at least 15 wt % HAP was added, the tensile modulus increased to 6 fold over conventional polycaprolactone.
  • Using the assumptions and criteria presented in Example 4, the combinations of materials and devices of the present invention, provided below in Table II, were selected: [0591]
    TABLE II
    LOAD-BEARING OSTEOBIOLOGIC
    Component Component
    Combination Composition Balloon Composition Balloon
    1. Timmer Short lived Wise-foam lock Bezwada
    PPF
    2. PCL Short lived Cooper None
    3. PCL S-IPN Short lived Wise Bezwada
    4. CaPO4 Long lived CaPO4 None
    5. Wise PPF Long lived Mikos porogen None
    6. PMMA-PCL Permanent TBD TBD
    7. none none PLA beads Non-compliant
    8. none none Timmer w/porogen Reinforced stiff sidewalls
  • Combination 1 [0592]
  • In this example, the Timmer IPN composition is chosen as the load bearing composition in the strut because it has sufficient initial and long term strength, acceptable modulus, and is resorbable. [0593]
  • Since the Timmer composition contains monomers, it is desirable to contain the composition in an inflatable device during curing. Since the Timmer composition is relatively resistant to degradation, the inflatable device can be made of a resorbable material having a short half life. Since the strut should also act as the distractor, the balloon should be non-compliant. [0594]
  • The Wise composition is chosen as the osteobiologic composition because is forms a scaffold having a strength and modulus essentially similar to that of cancellous bone. It can be infiltrated in-situ with a hydrogel containing osteogenic cells and osteoinductive growth factors. [0595]
  • Since the Wise composition contains monomers, it is desirable to contain the composition in an inflatable device during curing. Since bone in-growth is desirable through the region occupied by the balloon, the inflatable device should be made of a resorbable material having a very short half life (such as one day). Since the Wise composition a 25% expansion during pore formation, it would be desirable for the balloon to be compliant to allow the Wise composition conform to the disc space contour. [0596]
  • Combination 2 [0597]
  • In this example, solid neat polycaprolactone is chosen as the load bearing composition in the strut because it has sufficient initial strength (15 MPa), is very resistant to degradation, has an acceptable modulus (0.5 GPa), and is resorbable. [0598]
  • Since solid polycaprolactone is relatively resistant to regradation, the inflatable device need not be relatively resistant to degradation, and so can be made of a resorbable material having a short half life. Since the strut should also act as the distractor, the balloon should be non-compliant. [0599]
  • The Cooper composition is chosen as the osteobiologic composition because it is flowable at 40° C., and degrades sufficiently within a few months to form an hydroxyapatite based-scaffold. Because of its low delivery temperature, certain dimer bone morphogenetic proteins can also be delivered during the injection of this composition. [0600]
  • Since the Cooper composition is fully biodegrable, there is no real need to contain the composition in an inflatable device. [0601]
  • However, if it would be desirable to inject enough of the Cooper composition to conform it to the disc space contour, then it may be desirable to contain it in an inflatable device. Since bone in-growth is desirable through the osteobiologic composition, the inflatable device should be made of a resorbable material having a very short half-life (such as one day). [0602]
  • Combination 3 [0603]
  • In this example, the polycaprolactone S-IPN composition (as reported in Hao) is chosen as the load bearing composition in the strut because it may have mechanical properties about 3-6 fold greater than neat polycaprolactone, and is resorbable. [0604]
  • Since the polycaprolactone-polycaprolactone composition contains monomers, it is desirable to contain the composition in an inflatable device during curing. Since the polycaprolactone composition is relatively resistant to degradation, the inflatable device can be made of a resorbable material having a short half life. Since the strut should also act as the distractor, the balloon should be non-compliant. [0605]
  • Combination 4 [0606]
  • In this example, CaPO[0607] 4 is chosen as the load bearing composition in the strut because it has sufficient initial and long term strength, acceptable modulus, and is resorbable.
  • Since CaPO[0608] 4 is very susceptable to degradation, the inflatable device need be relatively resistant to degradation, and so should be made of a resistant material that can contain the CaPO4 for at least one year. Since the strut should also act as the distractor, the balloon should be non-compliant. One material that is resistant and non-compliant is polyetherether ketone.
  • The CaPO[0609] 4 composition is chosen as the osteobiologic composition because it is flowable at body temperature, and degrades sufficiently within a few months to form an hydroxyapatite based-scaffold. Because of its delivery at body temperature, hydrogels containing temperature sensitive additives, such as osteogenic cells and osteoinductive components (such as bone morphogenetic proteins), can also be delivered during the injection of this composition.
  • Since the CaPO[0610] 4 composition is fully biodegradable, there is no real need to contain the composition in an inflatable device.
  • Combination 5 [0611]
  • In this example, the Wise composition is chosen as the load bearing composition in the strut because it has sufficient initial strength, acceptable modulus, and is resorb able. [0612]
  • Since the Wise composition is very susceptable to degradation, the inflatable device need be relatively resistant to degradation, and so should be made of a resistant material that can contain the Wise Composition for at least one year. Since the strut should also act as the distractor, the balloon should be non-compliant. One material that is resistant and non-compliant is polyetherether ketone. [0613]
  • The Mikos composition is chosen as the osteobiologic composition because it is injectable at body temperature, forms an in-situ scaffold in which hydrogels containing temperature sensitive additives, such as osteogenic cells and osteoinductive components (such as bone morphogenetic proteins), can be delivered. [0614]
  • Since a hydrogel should be injected into the Mikos composition during surgery, it is desirable to inect the Mikos composition without the aid of a balloon. [0615]
  • Combination 6 [0616]
  • In this example, which is disclosed in Mendez, [0617] JBMR (2002), 61:66-74, the entire teachings of which are incorporated herein by reference, CaPO4 is chosen as the load bearing composition in the strut because it has sufficient initial and long term strength, acceptable modulus, and is resorbable.
  • Since CaPO[0618] 4 is very susceptable to degradation, the inflatable device need be relatively resistant to degradation, and so should be made of a resistant material that can contain the CaPO4 for at least one year. Since the strut should also act as the distractor, the balloon should be non-compliant. One material that is resistant and non-compliant is polyetherether ketone.
  • Combination 7 [0619]
  • The polylactic acid beads are chosen as the matrix of the osteobiologic composition because they can be packed into the disc space at body temperature and heat bonded with hot water to form an in-situ formed scaffold. If the beads are selected to have a 2 mm diameter, the porosity of the resulting scaffold will be about 40 vol % with a pore size of about 500 um. Hydrogels containing temperature sensitive additives, such as osteogenic cells and osteoinductive components (such as bone morphogenetic proteins), can then be delivered the in-situ scaffold. [0620]
  • Since the packed beads must be packed into the disc space and then heat bonded with a high temperature fluid, it may be desirable to contain both the beads and the hot fluid in a balloon. [0621]
  • The Nitonol reinforced balloon is desirable because the reinforcements can help the balloon withstand the high pressures needed during packing. [0622]
  • Since the polylactic acid beads have sufficient initial and long term strength, acceptable modulus, there is no need for a strut. [0623]
  • [0624] Combination 8
  • Timmer polypropylene fumarate-polypropylene fumarate-diacrylate with tricalcium phosphate (Embodiment B) with 50 vol % porosity (or seeded hydrogel phase) will still have a 25 MPa compressive strength after one year. If it takes the whole disc space, only 11.3 MPa is required. 2×safety factor. [0625]
  • Equivalents [0626]
  • While this invention has been particularly shown and described with references to preferred embodiments thereof, it will be understood by those skilled in the art that various changes in form and details may be made therein without departing from the scope of the invention encompassed by the appended claims. [0627]

Claims (104)

What is claimed is:
1. An orthopedic device for implanting between adjacent vertebrae comprising:
an arcuate balloon; and
a hardenable material within said balloon.
2. The device of claim 1 wherein said device has a footprint that substantially corresponds to at least a portion of the perimeter of a vertebral endplate.
3. The device of claim 1 wherein the balloon has an upper area, a lower area, an anterior area and a posterior area, and whereupon filling the balloon, said anterior area is unequal to said posterior area.
4. The device of claim 3 wherein said upper and lower areas each have a footprint substantially corresponding to a rim of a vertebral endplate.
5. The device of claim 1 wherein the balloon is cylindrical and further wherein said device has a footprint that substantially corresponds to a central portion of a vertebral endplate.
6. The device of claim 1 wherein the balloon further includes metalic wires thereby providing imageable means.
7. The device of claim 1 wherein at least one said balloon defines a plurality of lumena.
8. The device of claim 1 wherein at least one said balloon comprises a resorbable, semi-permeable material selected from the group consisting of porous and non-porous films, fabrics (woven and non-woven) and foams.
9. The device of claim 1 wherein at least one said balloon includes a material selected from the group consisting of a polyolefin copolymers, polyethylene, polycarbonate, polyethylene terephthalate, an ether-ketone polymer, a woven fiber, a nonwoven fibers, a fabric and a metal mesh.
10. The device of claim 1 wherein the balloon defines at least one opening.
11. The device of claim 1 wherein at least one of said upper and lower areas include at least one outward projection.
12. The device of claim 11 wherein the outward projection includes polyetherether ketone (PEEK).
13. The device of claim 11 wherein the upper area includes at least one material selected from the group consisting of polyether block copolymer (PEBAX), acrylonitrile butadiene styrene (ABS), acrylonitrile styrene (ANS), delrin acetal; polyvinyl chloride (PVC), polyethylene napthalate (PEN), polybutylene terephthalate (PBT), polycarbonate, polyetherimide (PEI), polyether sulfone (PES), polyethylene terephthalate (PET), polyethylene terephthalate glycol (PETG), polyamide, aromatic polyamide, polyether, polyester, polymethylmethacrylate, polyurethane copolymer, ethylene vinyl acetate (EVA), ethylene vinyl alcohol, polyethylene, latex rubber, FEP, TFE, PFA, polypropylene, polyolefin, polysiloxane, liquid crystal polymer, ionomer, poly(ethylene-co-methacrylic) acid, silicone rubber, styrene acrylonitrile (SAN), nylon, polyether block amide and thermoplastic elastomer.
14. The device of claim 1 wherein the balloon contains a load-bearing component.
15. The device of claim 14 wherein the load-bearing material is a strut.
16. The device of claim 14 wherein the load-bearing component further includes at least one compound selected from the group consisting of antibacterial agents and antifungal agents.
17. The device of claim 14 wherein the load-bearing component further includes at least one antibody that has affinity for connective tissue progenitor stem cells.
18. The device of claim 14 wherein the load-bearing component further includes at least one member of the group consisting of vitamins, hormones, glycoproteins, fibronectin, peptides, proteins, carbohydrates, proteoglycans, antiangiogenic agents, oligonucleotides, bone morphogenetic proteins, demineralized bone matrix, antibodies and genetically altered cells.
19. The device of claim 14 wherein the load-bearing component further includes an osteobiologic component.
20. The device of claim 19 wherein the load-bearing component includes:
a) a polymer flowable at between about 40° C. and 80° C.;
b) mesenchymal stem cells; and
c) a bone morphogenetic protein.
21. The device of claim 20 wherein said polymer is selected from the group consisting of a linear anhydride and a fumarate.
22. The device of claim 14 wherein the load-bearing component is resorbable.
23. The device of claim 22 wherein the load-bearing component includes
a) a polymer that flows at a temperature of between about 40° C. and about 80° C. and is present in an amount of between 50% and 70% by volume; and
b) calcium phosphate compound present in an amount of between about 10% and about 30% by volume.
24. The device of claim 23 wherein said polymer is polycaprolactone and said calcium phosphate compound is hydroxyapatite.
25. The device of claim 14 wherein the sum total of load-bearing capacity of the resorbable load-bering material and a new bone growth is at least sufficient to support a spinal load between the vertebrae.
26. The device of claim 19 wherein the osteobiologic component is resorbable.
27. The device of claim 19 wherein the load-bearing component comprises at least one compound selected from the group consisting of poly(lactic acid), poly(glycolic acid), p-dioxanone fibers, polyarylethyl, polymethylmethacrylate, polyurethane, amino-acid-derived polycarbonate, polycaprolactone, aliphatic polyesters, calcium phosphate, unsaturated linear polyesters, vinyl pyrrolidone and polypropylene fumarate diacrylate.
28. The device of claim 27 wherein the load-bearing component comprises two cross-linkable polymer, and wherein, upon exposure to at least one cross-linking agent, each of the cross-linkable polymer cross-links with itself, thereby resulting in an interpenetrating network.
29. The device of claim 27 wherein the load-bearing component comprises a first cross-linkable polymer and a second cross-linkable polymer, and wherein, upon exposure to at least one cross-linking agent, the first cross-linkable polymer cross-links with itself, while the second cross-linkeable polymer remains unaffected, thereby resulting in a semi-interpenetrating network.
30. The device of claim 19 wherein the osteobiologic component includes at least one member selected from the group consisting of mesenchymal stem cells, growth factors, cancellous bone chips, hydroxyapatite, tri-calcium phosphate, polylactic acid, polyglycolic acid, polygalactic acid, polycaprolactone, polyethylene oxide, polypropylene oxide, polysulfone, polyethylene, polypropylene, hyaluronic acid, bioglass, gelatin, collagen and polymeric fibers.
31. The device of claim 30 wherein the mesencymal cells are mammalian mesenchymal stems cells encapsulated in polylysine and polyethyleneimine cross-linked alginate membranes.
32. The device of claim 19 wherein the osteobiologic material includes at least one member selected from the group consisting of an osteoinductive component and an osteoconductive component.
33. The device of claim 32 wherein the osteoinductive component includes at least one compound selected from the group consisting of fibroblast growth factor-1, fibroblast growth factor-2, fibroblast growth factor-4, platellet derived growth factor-AB, platellet derived growth factor-BB, platellet derived growth factor-AA, epithelial growth factors, insulin-like growth factor-I, insulin-like growth factor-II, osteogenic protein-1, transforming growth factors-β, transforming growth factors-β1, transforming growth factors-β2, transforming growth factors-β3; osteoid-inducing factor (OIF), angiogenin, endothelin, hepatocyte growth factor, keratinocyte growth factor, osteogenin, bone morphogenetic proteins-2; bone morphogenetic proteins-2A, bone morphogenetic proteins-2B, bone morphogenetic proteins-7; heparin-binding growth factors-1, heparin-binding growth factors-2, an isoform of platelet-derived growth factors, an isoform of fibroblast growth factors, an isoform of epithelial growth factors, an isoform of insulin-like growth factors, an isoform of bone morphogenic proteins, an isoform of growth differentiation factors, Indian hedgehog, sonic hedgehog, desert hedgehog, interleukin-1, interleukin-2, interleukin-3, interleukin-4, interleukin-5, interleukin-6, colony-stimulating factor-1, granulocyte-colony-stimulating factor and granulocyte-macrophage colony-stimulating factor.
34. The device of claim 32 wherein osteoconductive component includes a compound having the formula:
M2+ (10-n)N1+ 2n(ZO4 3-)6 mYx
where
n=1-10, and m=2 when x=1, and/or m=1 when x=2;
M and N are alkali or alkaline earth metals;
ZO4 is an acid radical, where Z is phosphorus, arsenic, vanadium, sulfur or silicon; and
Y is a halide, hydroxide, or carbonate.
35. The device of claim 32 wherein the osteoconductive component includes at least one material selected from the group consisting of mono-calcium phosphate, di-calcium phosphate, octa-calcium phosphate, alpha-tri-calcium phosphate, beta-tri-calcium phosphate, or tetra-calcium phosphate, hydroxyapatite, fluorapatite, calcium sulfate, calcium fluoride, calcium oxide, silicon dioxide, sodium oxide, and phosphorus pentoxide.
36. The device of claim 19 wherein at least one of the load-bearing or the osteobiologic components further includes at least one water-soluble material selected from the group consisting of gelatin, a salt, a polysaccharides and a protein.
37. The device of claim 36 wherein, upon dissolution of the water-soluble material, at least one of the load-bearing or osteobiologic components forms a porous matrix.
38. The device of claim 37 wherein, upon delivering additional osteobiologic component into the porous matrix, said additional osteobiologic material including osteoprogenitor cells, said cells adhere to inner surfaces of the pores of the porous matrix.
39. The device of claim 1 wherein, upon at least partially filling the balloon, at least a portion of the device has a generally toroidal shape thereby defining an open cavity having an axial dimension and a radial dimension.
40. The device of claim 39 wherein said balloon has a footprint that describes an arc of at least about 200 degrees.
41. The device of claim 39 wherein said open cavity is filled with a load-bearing material.
42. The device of claim 41 wherein the load-bearing material that fills said open cavity further includes an osteobiologic component.
43. An intervertebral spinal fusion device comprising at least one arcuate inflatable balloon whereby at least partially filling the balloon between two adjacent vertebrae at least partially restores a natural angle between the adjacent vertebrae, and wherein said asymetric balloon contains a load-bearing component within a lumen defined by the balloon.
44. The device of claim 43 wherein said device has a footprint that substantially corresponds to a perimeter of a vertebral endplate.
45. The device of claim 43 wherein the load-bering component includes an osteobiologic component.
46. The device of claim 45 wherein the load-bearing component includes at least one compound selected from the group consisting of poly(lactic acid), poly(glycolic acid), p-dioxanone fibers, polyarylethyl, polymethylmethacrylate, polyurethane, amino-acid-derived polycarbonate, polycaprolactone, aliphatic polyesters, calcium phosphate, unsaturated linear polyesters, vinyl pyrrolidone and polypropylene fumarate diacrylate or mixtures thereof.
47. The device of claim 46 wherein, the balloon has an inner surface that is chemically active, whereby the load-bearing component chemically bonds to the balloon while it polymerizes.
48. An intervertebral spinal fusion device comprising:
a) an anterior frame having an upper inflatable rim and a lower inflatable rim, said anterior frame being detachably connected to a first fluid communication means; and
b) a rigid inflatable posterior frame attached to the upper and lower inflatable rims of the anterior frame, said posterior frame being detachably connected to a second fluid communication means,
wherein, upon at least partially filling the upper and lower inflatable rims and the posterior frame between two adjacent vertebrae, a natural angle between said vertebrae is at least partially restored.
49. The device of claim 48 wherein the anterior frame is partially rigid.
50. The device of claim 48 wherein, upon filling the upper and the lower inflatable rims and the posterior frame, the distance between the upper and the lower inflatable rims is different from the height the posterior frame.
51. The device of claim 49 wherein, upon at least partially filling the upper and the lower inflatable rims, said rims each have a footprint substantially corresponding to a rim of a vertebral endplate.
52. The device of claim 51 wherein, upon at least partially filling the upper and the lower inflatable rims and the posterior frame, the device defines an open cavity having an axial and a radial dimension.
53. The device of claim 48 further comprising at least one mesh element connected to the upper and the lower rims of the anterior portion.
54. The device of claim 48 wherein at least one of the upper and the lower rims of the anterior portion includes at least one outward projection.
55. The device of claim 48 wherein the posterior portion further includes at least one telescopically inflatable supporting element, each said supporting element being connected to the upper and the lower rims of the posterior portion.
56. A method of implanting an intervertebral spinal fusion device, comprising the steps of:
a) performing a discectomy while preserving an outer annular shell;
b) inserting an inflatable device that includes a deflated arcuate balloon into an intervertebral space;
c) directing a hardenable material into the deflated arcuate balloon in an amount sufficient to inflate the balloon and distract the disc space.
57. A method of implanting an intervertebral spinal fusion device, comprising the steps of:
a) inserting an inflatable device through a cannula into an intervertebral space, said inflatable device including an arcuate balloon connected to at least one fluid communication means, wherein said inflatable device upon expansion between two adjacent vertebrae at least partially restores a natural angle between the adjacent vertebrae;
b) orienting said inflatable device so that upon expansion a natural angle between vertebrae will be at least partially restored;
c) directing a load-bearing component into the inflatable device through the fluid communication means.
58. The method of claim 57 wherein the load-bearing material is resorbable and wherein the sum total of load-bearing capacity of the resorbable load-bering material and a new bone growth is at least sufficient to support a spinal load between the vertebrae.
59. The method of claim 57 wherein the load-bearing material includes an osteobiologic component.
60. The method of claim 57 wherein the balloon upon inflation has a footprint that substantially corresponds to a perimeter of a vertebral endplate.
61. The method of claim 59 wherein the load-bearing component includes a hardenable material.
62. The method of claim 59 wherein said inflatable device includes at least one inflatable balloon, said device defining an upper area, a lower area, an anterior area and a posterior area, and whereupon filling of the balloon said anterior area is unequal to said posterior area and said upper and lower areas each has a footprint substantially corresponding to a rim of a vertebral endplate.
63. The method of claim 62 wherein the anterior area of the device is oriented to face an anterior aspect of a vertebra and the posterior area of the device is oriented to face a posterior aspect of the vertebra.
64. The method of claim 62 wherein the load-bearing component is directed into the balloon by directing said component through the fluid communication means, thereby causing the balloon to expand and directing the upper area and the lower area of the balloon against the respective vertebral endplates, thereby at least partially restoring a natural angle between the adjacent vertebrae.
65. The method of claim 62 wherein the balloon defines a plurality of lumena.
66. The method of claim 62 wherein the balloon includes a resorbable material selected from the group consisting of the group consisting of poly(lactic acid), poly(glycolic acid), p-dioxanone fiber, polyarylethyl, polymethylmethacrylate, polyurethane, amino-acid-derived polycarbonate, polycaprolactone, aliphatic polyester, calcium phosphate, unsaturated linear polyester, vinyl pyrrolidone and polypropylene fumarate diacrylate.
67. The method of claim 62 wherein at least one balloon includes at least one material selected from the group consisting a of polyolefin copolymer, polyethylene, polycarbonate, polyethylene terephthalate, an ether-ketone polymer, woven fiber, non-woven fiber, fabric and metal mesh.
68. The method of claim 62 wherein at least one of said upper and lower areas has a plurality of outward projections and further wherein said outward projections include polyetherether ketone (PEEK).
69. The method of claim 62 wherein the upper area is made from at least one material selected from the group consisting of polyether block copolymer (PEBAX), ABS (acrylonitrile butadiene styrene), ANS (acrylonitrile styrene), delrin acetal; PVC (polyvinyl chloride), PEN (polyethylene napthalate), PBT (polybutylene terephthalate), polycarbonate, PEI (polyetherimide), PES (polyether sulfone), PET (polyethylene terephthalate), PETG (polyethylene terephthalate glycol), polyamide, aromatic polyamide, polyether, polyester, polymethylmethacrylate, polyurethane copolymer, ethylene vinyl acetate (EVA), ethylene vinyl alcohol, polyethylene, latex rubber, fluorinated ethylene polymer (FEP), polytetrafluoroethylene (PTFE), perfluoro-alkoxyalkane (PFA), polypropylene, polyolefin, polysiloxane, liquid crystal polymer, ionomer, poly(ethylene-co-methacrylic) acid, silicone rubber, SAN (styrene acrylonitrile), nylon, polyether block amide and thermoplastic elastomers.
70. The method of claim 62 wherein the load-bearing component includes at least one compound selected from the group consisting of poly(lactic acid), poly(glycolic acid), p-dioxanone fibers, polyarylethyl, polymethylmethacrylate, polyurethane, amino-acid-derived polycarbonate, polycaprolactone, aliphatic polyester, calcium phosphate, unsaturated linear polyesters, vinyl pyrrolidone and polypropylene fumarate diacrylate.
71. The method of claim 62 wherein the osteobiologic component includes at least one member selected from the group consisting of mesenchymal stem cells, a growth factor, cancellous bone chips, hydroxyapatite, tri-calcium phosphate, polylactic acid, polyglycolic acid, polygalactic acid, polycaprolactone, polyethylene oxide, polypropylene oxide, polysulfone, polyethylene, polypropylene, hyaluronic acid, bioglass, gelatin, collagen and a polymeric fiber.
72. The method of claim 62 wherein the osteobiologic component further includes a at least one water-soluble material selected from the group consisting of gelatin, a salt, a polysaccharides and a protein.
73. The method of claim 45 further including the step of directing an aqueous fluid into into the load-bearing material thereby dissolving at least one said water-soluble material, thereby forming a porous matrix.
74. The method of claim 62 wherein the osteoinductive component includes at least one compound selected from the group consisting of fibroblast growth factor-1, fibroblast growth factor-2, fibroblast growth factor-4, platellet derived growth factor-AB, platellet derived growth factor-BB, platellet derived growth factor-AA, epithelial growth factors, insulin-like growth factor-I, insulin-like growth factor-II, osteogenic protein-1, transforming growth factors-β, transforming growth factors-β1, transforming growth factors-β2, transforming growth factors-β3; osteoid-inducing factor (OIF), angiogenin, endothelin, hepatocyte growth factor, keratinocyte growth factor, osteogenin, bone morphogenetic proteins-2; bone morphogenetic proteins-2A, bone morphogenetic proteins-2B, bone morphogenetic proteins-7; heparin-binding growth factors-1, heparin-binding growth factors-2, an isoform of platelet-derived growth factors, an isoform of fibroblast growth factors, an isoform of epithelial growth factors, an isoform of insulin-like growth factors, an isoform of bone morphogenic proteins, an isoform of growth differentiation factors, Indian hedgehog, sonic hedgehog, desert hedgehog, interleukin-1, interleukin-2, interleukin-3, interleukin-4, interleukin-5, interleukin-6, colony-stimulating factor-1, granulocyte-colony-stimulating factor and granulocyte-macrophage colony-stimulating factor.
75. The method of claim 62 wherein the osteobiologic component has the formula:
M2+ (10-n)N1+ 2n(ZO4 3-)6 mYx
where
n=1-10, and m=2 when x=1, and/or m=1 when x=2;
M and N are alkali or alkaline earth metals;
ZO4 is an acid radical, where Z is phosphorus, arsenic, vanadium, sulfur or silicon; and
Y is a halide, hydroxide, or carbonate.
76. The method of claim 62 wherein the osteobiologic component includes at least one material selected from the group consisting of mono-calcium phosphate, di-calcium phosphate, octa-calcium phosphate, alpha-tri-calcium phosphate, beta-tri-calcium phosphate, or tetra-calcium phosphate, hydroxyapatite, fluorapatite, calcium sulfate, calcium fluoride, calcium oxide, silicon dioxide, sodium oxide, and phosphorus pentoxide, or mixtures thereof.
77. The method of claim 57 wherein at least a portion of the device upon expansion has a substantially toroidal shape thereby forming an open cavity defined by an outer surface of the toroidal shape having an axial dimension and a radial dimension.
78. The method of claim 62 wherein at least a portion of the device is oriented so that the axial dimension of the open cavity is substantially parallel to a major axis of a spinal column of a patient in which the device has been implanted.
79. The method of claim 78 wherein the load-bearing material is directed into the open cavity defined by the expanded device.
80. The method of claim 78 wherein the load-bearing material includes an osteobiologic material.
81. A method of at least partially restoring a natural angle between two adjacent vertebrae, comprising the steps of:
a) inserting an inflatable device through a cannula into an intervertebral space;
b) orienting said inflatable device so that upon expansion of the device a natural angle between vertebrae will be at least partially restored; and
c) expanding said inflatable device by directing a load-bearing component into said inflatable device.
82. The method of claim 80 wherein said inflatable device includes at least one arcuate inflatable balloon and a fluid communication means attached to at least one balloon and wherein at least one ballon upon expansion between two adjacent vertebrae at least partially restores a natural angle between two adjacent vertebrae.
83. The method of claim 81 wherein wherein said inflatable balloon, said device defining an upper area, a lower area, an anterior area and a posterior area, and whereupon filling the balloon said anterior area is unequal to said posterior area and said upper and lower areas each have a footprint substantially corresponding to a rim of a vertebral endplate.
84. The method of claim 83 wherein the step of orienting said inflatable device includes orienting the anterior area of the device to face the anterior aspect of a vertebra and the posterior area of the device to face the posterior aspect of a vertebrae.
85. The method of claim 83 wherein the step of inflating said inflatable device includes introducing at least one of a load-bearing component and an osteobiologic component into said device by directing at least one component through the fluid communication means, thereby causing the lower area and the upper area of the device to engage the respective endplates and the anterior area of the device to be greater than the posterior area of the device, thereby at least partially restoring a natural angle between the adjacent vertebrae.
86. The method of claim 81 wherein the load-bearing material includes a hardenable material.
87. The method of claim 82 wherein at least a portion of the device upon expansion has a substantially toroidal shape thereby forming an open cavity defined by an outer surface of the toroidal shape and having an axial dimension and a radial dimension.
88. The method of claim 87 wherein the step of orienting said inflatable device includes orienting at least a portion of the device so that the axial dimension of the open cavity is substantially parallel to a major axis of a spinal column of a patient in which the device has been implanted.
89. The method of claim 81 further including the step of directing a load-bearing material into the open cavity.
90. The method of claim 89 wherein load-bearing material includes an osteobiologic component.
91. The method of claim 89 wherein the load-bearing material includes a hardenable material.
92. The method of claim 91 wherein the osteobiologic material further includes at least one water-soluble material selected from the group consisting of gelatin, a salt, a polysaccharide and a protein.
93. The method of claim 92 further including the step of directing an aqueous fluid into the open cavity defined by the inflated device thereby dissolving at least one said water-soluble material and forming a porous matrix.
94. A method of delivering an osteobiologic material comprising:
a) inserting an inflatable device into an intervertebral space wherein at least a portion of the device upon expansion has a substantially toroidal shape thereby forming an open cavity defined by an outer surface of the toroidal shape and having an axial dimension and a radial dimension;
b) orienting at least a portion of the device so that so that the axial dimension of the open cavity is substantially parallel to a major axis of a spinal column of a patient in which the device has been implanted;
c) inflating said inflatable device by directing a load-bearing component into said inflatable device;
d) directing an osteobiologic material into the open cavity, said material including at least one water-soluble material;
95. The method of claim 94 further including the steps of:
e) directing an aqueous fluid into into the open cavity defined by the inflated device thereby dissolving at least one said water-soluble material, and forming a porous matrix; and
f) delivering additional osteobiologic component into the porous matrix in the amount sufficient to fill at least 90% of the porous matrix by volume.
96. An intervertebral fusion device comprising an in-situ formed osteobiologic component comprising:
a) a matrix having an internal surface defining an open porosity suitable for bone growth therethrough, and
b) an osteogenic component located within the open porosity.
97. An intervertebral fusion device for providing bony fusion across a disc space, comprising:
a) an in-situ formed strut having a upper surface for bearing against the upper endplate and a lower surface for bearing against the lower endplate, and
b) an in-situ formed osteobiologic porous matrix.
98. An intervertebral fusion device for providing bony fusion across a disc space, comprising an in-situ formed strut comprising:
a) an upper surface for bearing against the upper endplate,
b) a lower surface for bearing against the lower endplate, and
c) an injectable load bearing composition disposed between the upper and lower surfaces.
99. An intervertebral fusion device comprising a matrix having an internal surface defining an open porosity suitable for bone growth therethrough, wherein the matrix is formed by a plurality of in-situ bonded beads.
100. An intervertebral fusion device comprising a strut comprising:
a) a first component comprising:
i) a lower bearing surface adapted for bearing against a lower vertebral endplate, and,
ii) an upper surface comprising a leading end, an angled middle portion and a trailing end; and
b) a second component comprising:
i) an upper bearing surface adapted for bearing against an upper vertebral endplate, and,
ii) an upper surface comprising a leading end, an angled middle portion and a trailing end,
wherein the angled portion of the first component mates with the angled portion of the second component.
101. A kit for providing interbody fusion across an intervertebral disc space, comprising:
a) a cannula defining an inner diameter;
b) a hardenable material capable of supporting intervertebral load;
c) a flowable osteobiologic composition; and
d) an arcuate balloon.
102. An intervertebral fusion device for providing bony fusion across a disc space, comprising:
a) an in-situ formed strut having an upper surface for bearing against an upper endplate and a lower surface for bearing against a lower endplate, the upper surface and lower surface defining a height there between, and
b) an in-situ formed osteobiologic component,
wherein the height of the strut is no greater than the height of the disc space.
103. A method of providing interbody fusion across an intervertebral disc space, comprising the steps of:
a) providing a cannula defining an inner diameter;
b) moving a load bearing composition through the cannula and into the disc space to form a in-situ formed load bearing arcuate strut; and
c) moving an osteobiologic composition through the cannula and into the disc space to form an in-situ formed osteobiologic composition.
104. An intervertebral fusion device for providing bony fusion across a disc space, comprising an arcuate strut comprising:
a) an upper surface for bearing against the upper endplate,
b) a lower surface for bearing against the lower endplate, and
wherein the strut comprises an in-situ formed load bearing composition.
US10/778,684 2003-02-14 2004-02-13 In-situ formed intervertebral fusion device and method Abandoned US20040230309A1 (en)

Priority Applications (27)

Application Number Priority Date Filing Date Title
US10/778,684 US20040230309A1 (en) 2003-02-14 2004-02-13 In-situ formed intervertebral fusion device and method
US13/490,743 US11432938B2 (en) 2003-02-14 2012-06-07 In-situ intervertebral fusion device and method
US14/632,875 US9730803B2 (en) 2003-02-14 2015-02-26 Method of in-situ formation of an intervertebral fusion device
US14/640,741 US9439776B2 (en) 2003-02-14 2015-03-06 In-situ formed intervertebral fusion device and method
US14/668,576 US9801729B2 (en) 2003-02-14 2015-03-25 In-situ formed intervertebral fusion device and method
US14/674,070 US9439777B2 (en) 2003-02-14 2015-03-31 In-situ formed intervertebral fusion device and method
US14/684,959 US9333091B2 (en) 2003-02-14 2015-04-13 In-situ formed intervertebral fusion device and method
US14/856,716 US9814589B2 (en) 2003-02-14 2015-09-17 In-situ formed intervertebral fusion device and method
US14/875,983 US9808351B2 (en) 2003-02-14 2015-10-06 In-situ formed intervertebral fusion device and method
US14/886,302 US9788963B2 (en) 2003-02-14 2015-10-19 In-situ formed intervertebral fusion device and method
US14/886,362 US9814590B2 (en) 2003-02-14 2015-10-19 In-situ formed intervertebral fusion device and method
US14/934,289 US9724207B2 (en) 2003-02-14 2015-11-06 In-situ formed intervertebral fusion device and method
US15/074,725 US20160199196A1 (en) 2003-02-14 2016-03-18 In-situ formed intervertebral fusion device and method
US15/188,179 US10085843B2 (en) 2003-02-14 2016-06-21 In-situ formed intervertebral fusion device and method
US15/201,472 US10575959B2 (en) 2003-02-14 2016-07-03 In-situ formed intervertebral fusion device and method
US15/206,734 US10786361B2 (en) 2003-02-14 2016-07-11 In-situ formed intervertebral fusion device and method
US15/209,080 US10492918B2 (en) 2003-02-14 2016-07-13 In-situ formed intervertebral fusion device and method
US15/218,362 US10583013B2 (en) 2003-02-14 2016-07-25 In-situ formed intervertebral fusion device and method
US15/219,360 US10433971B2 (en) 2003-02-14 2016-07-26 In-situ formed intervertebral fusion device and method
US15/226,367 US10420651B2 (en) 2003-02-14 2016-08-02 In-situ formed intervertebral fusion device and method
US15/260,465 US9925060B2 (en) 2003-02-14 2016-09-09 In-situ formed intervertebral fusion device and method
US15/331,978 US10639164B2 (en) 2003-02-14 2016-10-24 In-situ formed intervertebral fusion device and method
US15/648,053 US10555817B2 (en) 2003-02-14 2017-07-12 In-situ formed intervertebral fusion device and method
US15/806,363 US10405986B2 (en) 2003-02-14 2017-11-08 In-situ formed intervertebral fusion device and method
US15/825,240 US10376372B2 (en) 2003-02-14 2017-11-29 In-situ formed intervertebral fusion device and method
US16/133,361 US11096794B2 (en) 2003-02-14 2018-09-17 In-situ formed intervertebral fusion device and method
US16/548,239 US11207187B2 (en) 2003-02-14 2019-08-22 In-situ formed intervertebral fusion device and method

Applications Claiming Priority (2)

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US44822103P 2003-02-14 2003-02-14
US10/778,684 US20040230309A1 (en) 2003-02-14 2004-02-13 In-situ formed intervertebral fusion device and method

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US13/490,743 Continuation US11432938B2 (en) 2003-02-14 2012-06-07 In-situ intervertebral fusion device and method

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US10/778,684 Abandoned US20040230309A1 (en) 2003-02-14 2004-02-13 In-situ formed intervertebral fusion device and method
US13/490,743 Active 2026-04-07 US11432938B2 (en) 2003-02-14 2012-06-07 In-situ intervertebral fusion device and method
US14/632,875 Expired - Lifetime US9730803B2 (en) 2003-02-14 2015-02-26 Method of in-situ formation of an intervertebral fusion device
US14/640,741 Expired - Lifetime US9439776B2 (en) 2003-02-14 2015-03-06 In-situ formed intervertebral fusion device and method
US14/668,576 Expired - Lifetime US9801729B2 (en) 2003-02-14 2015-03-25 In-situ formed intervertebral fusion device and method
US14/674,070 Expired - Lifetime US9439777B2 (en) 2003-02-14 2015-03-31 In-situ formed intervertebral fusion device and method
US14/684,959 Expired - Lifetime US9333091B2 (en) 2003-02-14 2015-04-13 In-situ formed intervertebral fusion device and method
US14/856,716 Expired - Lifetime US9814589B2 (en) 2003-02-14 2015-09-17 In-situ formed intervertebral fusion device and method
US14/875,983 Expired - Lifetime US9808351B2 (en) 2003-02-14 2015-10-06 In-situ formed intervertebral fusion device and method
US14/886,362 Expired - Lifetime US9814590B2 (en) 2003-02-14 2015-10-19 In-situ formed intervertebral fusion device and method
US14/886,302 Expired - Lifetime US9788963B2 (en) 2003-02-14 2015-10-19 In-situ formed intervertebral fusion device and method
US14/934,289 Expired - Lifetime US9724207B2 (en) 2003-02-14 2015-11-06 In-situ formed intervertebral fusion device and method
US15/074,725 Abandoned US20160199196A1 (en) 2003-02-14 2016-03-18 In-situ formed intervertebral fusion device and method
US15/188,179 Expired - Lifetime US10085843B2 (en) 2003-02-14 2016-06-21 In-situ formed intervertebral fusion device and method
US15/201,472 Expired - Lifetime US10575959B2 (en) 2003-02-14 2016-07-03 In-situ formed intervertebral fusion device and method
US15/206,734 Expired - Lifetime US10786361B2 (en) 2003-02-14 2016-07-11 In-situ formed intervertebral fusion device and method
US15/209,080 Active 2025-01-05 US10492918B2 (en) 2003-02-14 2016-07-13 In-situ formed intervertebral fusion device and method
US15/218,362 Active 2025-10-13 US10583013B2 (en) 2003-02-14 2016-07-25 In-situ formed intervertebral fusion device and method
US15/219,360 Expired - Lifetime US10433971B2 (en) 2003-02-14 2016-07-26 In-situ formed intervertebral fusion device and method
US15/226,367 Expired - Lifetime US10420651B2 (en) 2003-02-14 2016-08-02 In-situ formed intervertebral fusion device and method
US15/260,465 Expired - Lifetime US9925060B2 (en) 2003-02-14 2016-09-09 In-situ formed intervertebral fusion device and method
US15/331,978 Active 2024-08-31 US10639164B2 (en) 2003-02-14 2016-10-24 In-situ formed intervertebral fusion device and method
US15/648,053 Expired - Lifetime US10555817B2 (en) 2003-02-14 2017-07-12 In-situ formed intervertebral fusion device and method
US15/806,363 Expired - Lifetime US10405986B2 (en) 2003-02-14 2017-11-08 In-situ formed intervertebral fusion device and method
US15/825,240 Expired - Lifetime US10376372B2 (en) 2003-02-14 2017-11-29 In-situ formed intervertebral fusion device and method
US16/133,361 Active 2024-06-13 US11096794B2 (en) 2003-02-14 2018-09-17 In-situ formed intervertebral fusion device and method
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US13/490,743 Active 2026-04-07 US11432938B2 (en) 2003-02-14 2012-06-07 In-situ intervertebral fusion device and method
US14/632,875 Expired - Lifetime US9730803B2 (en) 2003-02-14 2015-02-26 Method of in-situ formation of an intervertebral fusion device
US14/640,741 Expired - Lifetime US9439776B2 (en) 2003-02-14 2015-03-06 In-situ formed intervertebral fusion device and method
US14/668,576 Expired - Lifetime US9801729B2 (en) 2003-02-14 2015-03-25 In-situ formed intervertebral fusion device and method
US14/674,070 Expired - Lifetime US9439777B2 (en) 2003-02-14 2015-03-31 In-situ formed intervertebral fusion device and method
US14/684,959 Expired - Lifetime US9333091B2 (en) 2003-02-14 2015-04-13 In-situ formed intervertebral fusion device and method
US14/856,716 Expired - Lifetime US9814589B2 (en) 2003-02-14 2015-09-17 In-situ formed intervertebral fusion device and method
US14/875,983 Expired - Lifetime US9808351B2 (en) 2003-02-14 2015-10-06 In-situ formed intervertebral fusion device and method
US14/886,362 Expired - Lifetime US9814590B2 (en) 2003-02-14 2015-10-19 In-situ formed intervertebral fusion device and method
US14/886,302 Expired - Lifetime US9788963B2 (en) 2003-02-14 2015-10-19 In-situ formed intervertebral fusion device and method
US14/934,289 Expired - Lifetime US9724207B2 (en) 2003-02-14 2015-11-06 In-situ formed intervertebral fusion device and method
US15/074,725 Abandoned US20160199196A1 (en) 2003-02-14 2016-03-18 In-situ formed intervertebral fusion device and method
US15/188,179 Expired - Lifetime US10085843B2 (en) 2003-02-14 2016-06-21 In-situ formed intervertebral fusion device and method
US15/201,472 Expired - Lifetime US10575959B2 (en) 2003-02-14 2016-07-03 In-situ formed intervertebral fusion device and method
US15/206,734 Expired - Lifetime US10786361B2 (en) 2003-02-14 2016-07-11 In-situ formed intervertebral fusion device and method
US15/209,080 Active 2025-01-05 US10492918B2 (en) 2003-02-14 2016-07-13 In-situ formed intervertebral fusion device and method
US15/218,362 Active 2025-10-13 US10583013B2 (en) 2003-02-14 2016-07-25 In-situ formed intervertebral fusion device and method
US15/219,360 Expired - Lifetime US10433971B2 (en) 2003-02-14 2016-07-26 In-situ formed intervertebral fusion device and method
US15/226,367 Expired - Lifetime US10420651B2 (en) 2003-02-14 2016-08-02 In-situ formed intervertebral fusion device and method
US15/260,465 Expired - Lifetime US9925060B2 (en) 2003-02-14 2016-09-09 In-situ formed intervertebral fusion device and method
US15/331,978 Active 2024-08-31 US10639164B2 (en) 2003-02-14 2016-10-24 In-situ formed intervertebral fusion device and method
US15/648,053 Expired - Lifetime US10555817B2 (en) 2003-02-14 2017-07-12 In-situ formed intervertebral fusion device and method
US15/806,363 Expired - Lifetime US10405986B2 (en) 2003-02-14 2017-11-08 In-situ formed intervertebral fusion device and method
US15/825,240 Expired - Lifetime US10376372B2 (en) 2003-02-14 2017-11-29 In-situ formed intervertebral fusion device and method
US16/133,361 Active 2024-06-13 US11096794B2 (en) 2003-02-14 2018-09-17 In-situ formed intervertebral fusion device and method
US16/548,239 Active 2024-08-21 US11207187B2 (en) 2003-02-14 2019-08-22 In-situ formed intervertebral fusion device and method

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Cited By (316)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20040220534A1 (en) * 2003-04-29 2004-11-04 Martens Paul W. Medical device with antimicrobial layer
US20050113919A1 (en) * 2000-02-16 2005-05-26 Cragg Andrew H. Prosthetic nucleus apparatus
US20050113923A1 (en) * 2003-10-03 2005-05-26 David Acker Prosthetic spinal disc nucleus
US20050187140A1 (en) * 2003-11-20 2005-08-25 Angiotech International Ag Polymer compositions and methods for their use
US20060004358A1 (en) * 2004-06-30 2006-01-05 Depuy Spine, Inc. In-situ formed posterolateral fusion system
US20060052874A1 (en) * 2004-09-09 2006-03-09 Johnson Wesley M Prostheses for spine discs having fusion capability
US20060079898A1 (en) * 2003-10-23 2006-04-13 Trans1 Inc. Spinal motion preservation assemblies
US20060089652A1 (en) * 2004-10-26 2006-04-27 Concept Matrix, Llc Working channel for minimally invasive spine surgery
US20060106461A1 (en) * 2004-11-12 2006-05-18 Embry Jill M Implantable vertebral lift
US20060149380A1 (en) * 2004-12-01 2006-07-06 Lotz Jeffrey C Systems, devices and methods for treatment of intervertebral disorders
US20060155297A1 (en) * 2003-10-23 2006-07-13 Ainsworth Stephen D Driver assembly for simultaneous axial delivery of spinal implants
US20060200245A1 (en) * 2005-03-07 2006-09-07 Sdgi Holdings, Inc. Materials, devices, and methods for in-situ formation of composite intervertebral implants
US20060206209A1 (en) * 2003-10-23 2006-09-14 Cragg Andrew H Prosthetic nucleus apparatus and methods
US20060217810A1 (en) * 2005-03-24 2006-09-28 Toussaint Leclercq Artifical lumbar disc
WO2006111174A1 (en) * 2005-04-16 2006-10-26 Aesculap Ag & Co. Kg Implant for alleviating pressure on intervertebral disks and method for the adjustment and pressure alleviation of an intervertebral space
US20060247625A1 (en) * 2005-04-29 2006-11-02 Sdgi Holdings, Inc. System, devices and method for augmenting existing fusion constructs
US20060247783A1 (en) * 2005-04-30 2006-11-02 Mckay William F Spinal fusion with osteogenic material and migration barrier
US20060265077A1 (en) * 2005-02-23 2006-11-23 Zwirkoski Paul A Spinal repair
US20060287727A1 (en) * 2005-06-15 2006-12-21 Jerome Segal Mechanical apparatus and method for artificial disc replacement
US20060287730A1 (en) * 2005-06-15 2006-12-21 Jerome Segal Mechanical apparatus and method for artificial disc replacement
US20070021835A1 (en) * 2005-07-11 2007-01-25 Edidin Avram A Systems and methods for providing prostheses
US20070027544A1 (en) * 2005-07-28 2007-02-01 Altiva Corporation Spinal cage implant
US20070067036A1 (en) * 2005-09-20 2007-03-22 Zimmer Spine, Inc. Hydrogel total disc prosthesis
US20070073398A1 (en) * 2005-09-27 2007-03-29 Fabian Henry F Spine surgery method and implant
US20070078477A1 (en) * 2005-02-04 2007-04-05 Heneveld Scott H Sr Anatomical spacer and method to deploy
US20070093899A1 (en) * 2005-09-28 2007-04-26 Christof Dutoit Apparatus and methods for treating bone
US20070118218A1 (en) * 2005-11-22 2007-05-24 Hooper David M Facet joint implant and procedure
US20070123986A1 (en) * 2005-08-16 2007-05-31 Laurent Schaller Methods of Distracting Tissue Layers of the Human Spine
US20070149690A1 (en) * 2005-12-23 2007-06-28 Boston Scientific Scimed, Inc. Functionalized block copolymers
US20070168036A1 (en) * 2003-10-23 2007-07-19 Trans1 Inc. Spinal motion preservation assemblies
WO2006118803A3 (en) * 2005-04-29 2007-07-26 Warsaw Orthopedic Inc Synthetic loadbearing collagen-mineral composites for spinal implants
US20070173935A1 (en) * 2005-10-28 2007-07-26 O'neil Michael J Nucleus pulposus augmentation pretreatment technique
US20070185231A1 (en) * 2006-01-23 2007-08-09 Liu Y K Bone cement composite containing particles in a non-uniform spatial distribution and devices for implementation
US20070190083A1 (en) * 2006-02-01 2007-08-16 Scifert Jeffrey L Medical implants with reservoir (s), and materials preparable from same
WO2007092559A2 (en) * 2006-02-08 2007-08-16 Northwestern University A poly (diol-co-citrate) hydroxyapatite composite for tissue engineering and orthopaedic fixation devices
US20070233246A1 (en) * 2006-03-31 2007-10-04 Sdgi Holdings, Inc. Spinal implants with improved mechanical response
US20070260315A1 (en) * 2006-05-03 2007-11-08 Foley Kevin T Devices and methods for disc height restoration
US20070270953A1 (en) * 2006-03-29 2007-11-22 Sdgi Holdings, Inc. Transformable spinal implants and methods of use
US20070270971A1 (en) * 2006-03-14 2007-11-22 Sdgi Holdings, Inc. Intervertebral prosthetic disc with improved wear resistance
US20070270970A1 (en) * 2006-03-14 2007-11-22 Sdgi Holdings, Inc. Spinal implants with improved wear resistance
US20070299523A1 (en) * 2006-06-08 2007-12-27 Francis Pflum Sac for use in spinal surgery
US20080009944A1 (en) * 2001-10-02 2008-01-10 Rex Medical Spinal implant and method of use
US20080021557A1 (en) * 2006-07-24 2008-01-24 Warsaw Orthopedic, Inc. Spinal motion-preserving implants
US20080021556A1 (en) * 2006-07-21 2008-01-24 Edie Jason A Expandable vertebral implant and methods of use
US20080021462A1 (en) * 2006-07-24 2008-01-24 Warsaw Orthopedic Inc. Spinal stabilization implants
WO2008018096A1 (en) * 2006-08-08 2008-02-14 Radames Binotto Intervertebral spacer with applicator device
US20080039854A1 (en) * 2006-04-26 2008-02-14 Illuminoss Medical, Inc. Apparatus and methods for delivery of reinforcing materials to bone
US20080058932A1 (en) * 2006-07-26 2008-03-06 Warsaw Orthopedic Inc. Rigidization-on-command orthopedic devices and methods
WO2008051254A1 (en) * 2006-10-27 2008-05-02 The Regents Of The University Of Colorado A polymer formulation a method of determining a polymer formulation and a method of determining a polymer fabrication
US20080109003A1 (en) * 2006-11-08 2008-05-08 Peckham Steven M Methods of employing calcium phosphate cement compositions and osteoinductive proteins to effect vertebrae interbody fusion absent an interbody device
US20080119851A1 (en) * 2006-11-20 2008-05-22 Depuy Spine, Inc. Anterior spinal vessel protector
US20080133012A1 (en) * 2006-11-16 2008-06-05 Mcguckin James F Spinal implant and method of use
US20080140201A1 (en) * 2006-12-08 2008-06-12 Shawn Stad Nucleus Replacement Device and Method
US20080154368A1 (en) * 2006-12-21 2008-06-26 Warsaw Orthopedic, Inc. Curable orthopedic implant devices configured to harden after placement in vivo by application of a cure-initiating energy before insertion
US20080154234A1 (en) * 2006-12-20 2008-06-26 Zimmer Orthobiologics, Inc. Apparatus and method for delivering a biocompatible material to a surgical site
US20080154373A1 (en) * 2006-12-21 2008-06-26 Warsaw Orthopedic, Inc. Curable orthopedic implant devices configured to be hardened after placement in vivo
US20080167685A1 (en) * 2007-01-05 2008-07-10 Warsaw Orthopedic, Inc. System and Method For Percutanously Curing An Implantable Device
WO2008094217A1 (en) * 2007-01-31 2008-08-07 Ouroboros, Inc. Mechanical apparatus and method for artificial disc replacement
US20080249633A1 (en) * 2006-08-22 2008-10-09 Tim Wu Biodegradable Materials and Methods of Use
US20080262502A1 (en) * 2006-10-24 2008-10-23 Trans1, Inc. Multi-membrane prosthetic nucleus
US20080262633A1 (en) * 2006-05-08 2008-10-23 Williams Michelle Leroux Cancellous bone treated with collagenase and essentially free of blood cells
US20090005870A1 (en) * 2007-06-26 2009-01-01 John Riley Hawkins Highly Lordosed Fusion Cage
US20090012623A1 (en) * 2007-07-07 2009-01-08 Jmea Corporation Disk Fusion Implant
US20090060972A1 (en) * 2005-11-21 2009-03-05 Nicast Ltd. Device and method for cell grafting
US20090069900A1 (en) * 2007-09-11 2009-03-12 Bezaleel, Llc. Method for forming a bioresorbable composite implant in a bone
US20090088789A1 (en) * 2007-09-28 2009-04-02 O'neil Michael J Balloon With Shape Control For Spinal Procedures
US20090104586A1 (en) * 2005-06-01 2009-04-23 Osseous Technologies Of America Collagen Antral Membrane Expander
US20090112323A1 (en) * 2007-10-29 2009-04-30 Zimmer Spine, Inc. Minimally invasive interbody device and method
US20090136576A1 (en) * 2005-06-20 2009-05-28 Giuseppe Calvosa Biocompatible composition for replacing/regenerating tissues
US20090163958A1 (en) * 2007-12-20 2009-06-25 Peter Tarcha Compositions, devices, systems, and methods for inhibiting an inflammatory response
US20090169597A1 (en) * 2007-12-27 2009-07-02 Ethicon, Incorporated Treatment of intervertebral disc degeneration using human umbilical cord tissue-derived cells
US20090234457A1 (en) * 2001-06-29 2009-09-17 The Regents Of The University Of California Systems, devices and methods for treatment of intervertebral disorders
US20090246244A1 (en) * 2008-03-27 2009-10-01 Warsaw Orthopedic, Inc. Malleable multi-component implants and materials therefor
US20090259177A1 (en) * 2005-02-16 2009-10-15 Susan Lynn Riley Resorbable hollow devices for implantation and delivery of therapeutic agents
US20090270987A1 (en) * 2008-04-24 2009-10-29 Warsaw Orthopedic, Inc. Expandable vertebral implants and methods of use
US7655028B2 (en) 2003-09-30 2010-02-02 X-Spine Systems, Inc. Spinal fusion system and method for fusing spinal bones
US20100036503A1 (en) * 2008-08-07 2010-02-11 Chen Silvia S Composition for a Tissue Repair Implant and Methods of Making the Same
US20100041770A1 (en) * 2006-10-31 2010-02-18 Synthes Usa, Llc Polymer-ceramic composite and method
US20100114107A1 (en) * 2000-08-30 2010-05-06 Warsaw Orthopedic, Inc. Intervertebral Disc Nucleus Implants and Methods
US7727262B2 (en) 2000-06-23 2010-06-01 Warsaw Orthopedic, Inc. Formed in place fixation system with thermal acceleration
US20100145462A1 (en) * 2006-10-24 2010-06-10 Trans1 Inc. Preformed membranes for use in intervertebral disc spaces
US20100145454A1 (en) * 2008-12-09 2010-06-10 Zimmer Spine, Inc. Intervertebral disc nucleus replacement prosthesis
US20100173009A1 (en) * 2009-01-08 2010-07-08 Iain Ronald Gibson Silicate-substituted hydroxyapatite
US7754246B2 (en) 2005-09-09 2010-07-13 Wright Medical Technology, Inc. Composite bone graft substitute cement and articles produced therefrom
US7776042B2 (en) 2002-12-03 2010-08-17 Trans1 Inc. Methods and apparatus for provision of therapy to adjacent motion segments
US20100241229A1 (en) * 2007-07-03 2010-09-23 Synergy Biosurgical Ag Medical implant
WO2010109460A1 (en) * 2009-03-23 2010-09-30 Chi 2 Gel Ltd. Restorative device for intervertebral discs
US20100256766A1 (en) * 2009-04-07 2010-10-07 Hibri Nadi S Percutaneous Implantable Nuclear Prosthesis
US7811284B2 (en) * 2006-11-10 2010-10-12 Illuminoss Medical, Inc. Systems and methods for internal bone fixation
US7811291B2 (en) 2007-11-16 2010-10-12 Osseon Therapeutics, Inc. Closed vertebroplasty bone cement injection system
US20100260723A1 (en) * 2007-05-02 2010-10-14 Aldemar Hegewald Implantable system for an intervertebral disc and intervertebral disc implant
US20100268155A1 (en) * 2009-04-20 2010-10-21 Warsaw Orthopedic, Inc. Method For Stabilizing An Intervertebral Disc Device
US7833249B2 (en) 2000-06-23 2010-11-16 Warsaw Orthopedic, Inc. Formable orthopedic fixation system
US20100324689A1 (en) * 2007-10-30 2010-12-23 Darren Donald Obrigkeit Implant comprising thermoplastic elastomer
US7879041B2 (en) 2006-11-10 2011-02-01 Illuminoss Medical, Inc. Systems and methods for internal bone fixation
US20110066192A1 (en) * 2009-09-15 2011-03-17 William Frasier Expandable Ring Intervertebral Fusion Device
US20110066244A1 (en) * 2009-09-11 2011-03-17 William Frasier Minimally Invasive Intervertebral Staple Distraction Devices
US20110087231A1 (en) * 2009-04-03 2011-04-14 Light Cure, Llc Devices and Injectable or Implantable Compositions for Intervertebral Fusion
US20110087329A1 (en) * 2009-10-13 2011-04-14 Nicholas Poulos Lumbar implant
US20110137317A1 (en) * 2009-12-07 2011-06-09 O'halloran Damien Methods and Apparatus For Treating Vertebral Fractures
US20110144753A1 (en) * 2009-12-10 2011-06-16 Connie Marchek Bellows-Like Expandable Interbody Fusion Cage
US7963982B2 (en) 2007-07-16 2011-06-21 X-Spine Systems, Inc. Implant plate screw locking system and screw having a locking member
US20110160870A1 (en) * 2009-11-30 2011-06-30 Adrian Baumgartner Expandable implant
US7988735B2 (en) * 2005-06-15 2011-08-02 Matthew Yurek Mechanical apparatus and method for delivering materials into the inter-vertebral body space for nucleus replacement
US20110202062A1 (en) * 2010-02-18 2011-08-18 O'halloran Damien Methods and Apparatus For Treating Vertebral Fractures
US20110213402A1 (en) * 2005-05-24 2011-09-01 Kyphon Sarl Low-compliance expandable medical device
US8025903B2 (en) 2005-09-09 2011-09-27 Wright Medical Technology, Inc. Composite bone graft substitute cement and articles produced therefrom
US20110238072A1 (en) * 2010-03-26 2011-09-29 Tyndall Dwight S Minimally Invasive Surgical (MIS) Technique and System for Performing an Interbody Lumbar Fusion with a Navigatable Intervertebral Disc Removal Device and Collapsible Intervertebral Device
US20110280838A1 (en) * 2007-12-27 2011-11-17 Advanced Technologies And Regenerative Medicine, Llc Treatment of intervertebral disc degeneration using human umbilical cord tissue-derived cells
US8062367B2 (en) 2003-09-30 2011-11-22 X-Spine Systems, Inc. Screw locking mechanism and method
US8066713B2 (en) 2003-03-31 2011-11-29 Depuy Spine, Inc. Remotely-activated vertebroplasty injection device
US8083774B2 (en) 2000-06-23 2011-12-27 Warsaw Orthopedic, Inc. Percutaneous vertebral fusion system
US20120010624A1 (en) * 2009-12-07 2012-01-12 O'halloran Damien Methods and Apparatus For Treating Vertebral Fractures
US20120046750A1 (en) * 2009-03-05 2012-02-23 Dsm Ip Assets B.V. Spinal fusion cage
US20120109329A1 (en) * 2009-07-10 2012-05-03 Milux Holding Sa Hip joint device, system and method
US20120130489A1 (en) * 2010-05-19 2012-05-24 Chernomorsky Ary S Methods and apparatus for in situ formation of surgical implants
US8197545B2 (en) 2005-10-27 2012-06-12 Depuy Spine, Inc. Nucleus augmentation delivery device and technique
WO2012088432A1 (en) * 2010-12-22 2012-06-28 Illuminoss Medical, Inc. Systems and methods for treating conditions and diseases of the spine
US8210729B2 (en) 2009-04-06 2012-07-03 Illuminoss Medical, Inc. Attachment system for light-conducting fibers
US8282682B2 (en) 2003-09-30 2012-10-09 X-Spine Systems, Inc. Fusion system and method for fusing spinal bones
US8337556B2 (en) 2000-06-23 2012-12-25 Sdgi Holdings, Inc. Curable media for implantable medical device
US20120330417A1 (en) * 2005-09-30 2012-12-27 Arthrodisc, L.L.C. Tapered arcuate intervertebral implant
US8348956B2 (en) 2006-04-26 2013-01-08 Illuminoss Medical, Inc. Apparatus and methods for reinforcing bone
US8361078B2 (en) 2003-06-17 2013-01-29 Depuy Spine, Inc. Methods, materials and apparatus for treating bone and other tissue
US8360629B2 (en) 2005-11-22 2013-01-29 Depuy Spine, Inc. Mixing apparatus having central and planetary mixing elements
US8366773B2 (en) 2005-08-16 2013-02-05 Benvenue Medical, Inc. Apparatus and method for treating bone
US8372152B2 (en) 2003-09-30 2013-02-12 X-Spine Systems, Inc. Spinal fusion system utilizing an implant plate having at least one integral lock and ratchet lock
US8403968B2 (en) 2007-12-26 2013-03-26 Illuminoss Medical, Inc. Apparatus and methods for repairing craniomaxillofacial bones using customized bone plates
US8415407B2 (en) 2004-03-21 2013-04-09 Depuy Spine, Inc. Methods, materials, and apparatus for treating bone and other tissue
US8435301B2 (en) 2002-08-15 2013-05-07 DePuy Synthes Products, LLC Artificial intervertebral disc implant
US8454617B2 (en) 2005-08-16 2013-06-04 Benvenue Medical, Inc. Devices for treating the spine
US8480757B2 (en) 2005-08-26 2013-07-09 Zimmer, Inc. Implants and methods for repair, replacement and treatment of disease
US20130178939A1 (en) * 2009-10-13 2013-07-11 Nicholas Poulos Expandable interbody implant and method
US8497121B2 (en) 2006-12-20 2013-07-30 Zimmer Orthobiologics, Inc. Method of obtaining viable small tissue particles and use for tissue repair
US8512338B2 (en) 2009-04-07 2013-08-20 Illuminoss Medical, Inc. Photodynamic bone stabilization systems and methods for reinforcing bone
US20130218278A1 (en) * 2012-02-21 2013-08-22 Steve Wolfe Device and method for performing spinal interbody fusion
US8518433B2 (en) 2003-12-11 2013-08-27 Zimmer, Inc. Method of treating an osteochondral defect
US8535327B2 (en) 2009-03-17 2013-09-17 Benvenue Medical, Inc. Delivery apparatus for use with implantable medical devices
US20130282121A1 (en) * 2012-03-22 2013-10-24 Ann Prewett Spinal facet augmentation implant and method
US20130297023A1 (en) * 2012-05-07 2013-11-07 Hee-Jeong Im Sampen Methods and Devices For Treating Intervertebral Disc Disease
US8579977B2 (en) 2008-04-24 2013-11-12 Henry F. Fabian Spine surgery method and inserter
US8579908B2 (en) 2003-09-26 2013-11-12 DePuy Synthes Products, LLC. Device for delivering viscous material
US8591583B2 (en) * 2005-08-16 2013-11-26 Benvenue Medical, Inc. Devices for treating the spine
US8663328B2 (en) 2006-12-21 2014-03-04 Warsaw Orthopedic, Inc. Methods for positioning a load-bearing component of an orthopedic implant device by inserting a malleable device that hardens in vivo
US20140088683A1 (en) * 2006-08-07 2014-03-27 W. L. Gore & Associates, Inc. Non-shortening wrapped balloon
US8684965B2 (en) 2010-06-21 2014-04-01 Illuminoss Medical, Inc. Photodynamic bone stabilization and drug delivery systems
US8702716B1 (en) 2009-09-21 2014-04-22 Reva Medical Inc. Devices, compositions and methods for bone and tissue augmentation
WO2014066808A1 (en) * 2012-10-25 2014-05-01 Rutgers, The State University Of New Jersey Insulin-mimetic local therapeutic adjuncts for enhancing spinal fusion
US8777618B2 (en) 2007-09-17 2014-07-15 Synergy Biosurgical Ag Medical implant II
US8814873B2 (en) 2011-06-24 2014-08-26 Benvenue Medical, Inc. Devices and methods for treating bone tissue
US8821553B2 (en) 2003-09-30 2014-09-02 X-Spine Systems, Inc. Spinal fusion system utilizing an implant plate having at least one integral lock
US8828082B2 (en) 2009-07-09 2014-09-09 R Tree Innovations, Llc Inter-body implant
US8827981B2 (en) 2007-11-16 2014-09-09 Osseon Llc Steerable vertebroplasty system with cavity creation element
US20140277464A1 (en) * 2013-03-14 2014-09-18 Synthes Usa, Llc Expandable coil spinal implant
US20140303730A1 (en) * 2011-11-30 2014-10-09 Beth Israel Deaconess Medical Center Systems and methods for endoscopic vertebral fusion
US8870965B2 (en) 2009-08-19 2014-10-28 Illuminoss Medical, Inc. Devices and methods for bone alignment, stabilization and distraction
US20140343689A1 (en) * 2006-03-14 2014-11-20 Kci Licensing, Inc. System and method for percutaneously administering reduced pressure treatment using a flowable manifold
US20140378980A1 (en) * 2013-06-24 2014-12-25 Roman Lomeli Cortical Rim-Supporting Interbody Device
WO2014140916A3 (en) * 2013-03-14 2015-01-08 Ranier Limited Intervertebral fusion implant cage
US8936644B2 (en) 2011-07-19 2015-01-20 Illuminoss Medical, Inc. Systems and methods for joint stabilization
US8936804B2 (en) 2010-01-15 2015-01-20 Rutgers, The State University Of New Jersey Use of vanadium compounds to accelerate bone healing
US8939977B2 (en) 2012-07-10 2015-01-27 Illuminoss Medical, Inc. Systems and methods for separating bone fixation devices from introducer
US8950929B2 (en) 2006-10-19 2015-02-10 DePuy Synthes Products, LLC Fluid delivery system
WO2014190289A3 (en) * 2013-05-23 2015-02-26 206 Ortho, Inc. Method and apparatus for treating bone fractures, and/or for fortifying and/or augmenting bone, including the provision and use of composite implants
US8992541B2 (en) 2003-03-14 2015-03-31 DePuy Synthes Products, LLC Hydraulic device for the injection of bone cement in percutaneous vertebroplasty
US9044333B2 (en) 2007-07-27 2015-06-02 R Tree Innovations, Llc Inter-body implantation system and method
US9060870B2 (en) 2012-02-05 2015-06-23 Michael J. Milella, Jr. In-situ formed spinal implant
US9078706B2 (en) 2003-09-30 2015-07-14 X-Spine Systems, Inc. Intervertebral fusion device utilizing multiple mobile uniaxial and bidirectional screw interface plates
US9125906B2 (en) 2005-12-28 2015-09-08 DePuy Synthes Products, Inc. Treatment of peripheral vascular disease using umbilical cord tissue-derived cells
US9138318B2 (en) 2007-04-12 2015-09-22 Zimmer, Inc. Apparatus for forming an implant
US9144633B2 (en) 2010-12-10 2015-09-29 Rutgers, The State University Of New Jersey Implantable devices coated with insulin-mimetic vanadium compounds and methods thereof
US9144442B2 (en) 2011-07-19 2015-09-29 Illuminoss Medical, Inc. Photodynamic articular joint implants and methods of use
US9211195B2 (en) 2009-10-13 2015-12-15 Nicholas Poulos Expandable interbody implant and method
US9265616B2 (en) 2010-08-10 2016-02-23 DePuy Synthes Products, Inc. Expandable implant
US9265794B2 (en) 2010-12-10 2016-02-23 Rutgers, The State University Of New Jersey Insulin-mimetics as therapeutic adjuncts for bone regeneration
US9271843B2 (en) 2005-09-27 2016-03-01 Henry F. Fabian Spine surgery method and implant
US9289240B2 (en) 2005-12-23 2016-03-22 DePuy Synthes Products, Inc. Flexible elongated chain implant and method of supporting body tissue with same
US9295479B2 (en) 2013-03-14 2016-03-29 Spinal Stabilization Technologies, Llc Surgical device
US9295562B2 (en) 2008-01-17 2016-03-29 DePuy Synthes Products, Inc. Expandable intervertebral implant and associated method of manufacturing the same
US9320614B2 (en) 2006-07-31 2016-04-26 DePuy Synthes Products, Inc. Spinal fusion implant
US9320615B2 (en) 2010-06-29 2016-04-26 DePuy Synthes Products, Inc. Distractible intervertebral implant
US9326799B2 (en) 2009-12-07 2016-05-03 Globus Medical, Inc. Methods and apparatus for treating vertebral fractures
US9333091B2 (en) 2003-02-14 2016-05-10 DePuy Synthes Products, Inc. In-situ formed intervertebral fusion device and method
US20160128834A1 (en) * 2013-06-19 2016-05-12 Meir Yakir Scaffold implant system
US9358123B2 (en) 2011-08-09 2016-06-07 Neuropro Spinal Jaxx, Inc. Bone fusion device, apparatus and method
US9358058B2 (en) 2012-11-05 2016-06-07 Globus Medical, Inc. Methods and apparatus for treating vertebral fractures
US9381024B2 (en) 2005-07-31 2016-07-05 DePuy Synthes Products, Inc. Marked tools
US9408875B2 (en) 2005-10-12 2016-08-09 Lifenet Health Compositions for repair of defects in tissues, and methods of making the same
US9414934B2 (en) 2008-04-05 2016-08-16 DePuy Synthes Products, Inc. Expandable intervertebral implant
US9427289B2 (en) 2007-10-31 2016-08-30 Illuminoss Medical, Inc. Light source
US9480574B2 (en) 2013-03-14 2016-11-01 Benvenue Medical, Inc. Spinal fusion implants and devices and methods for deploying such implants
US9510885B2 (en) 2007-11-16 2016-12-06 Osseon Llc Steerable and curvable cavity creation system
US9526525B2 (en) 2006-08-22 2016-12-27 Neuropro Technologies, Inc. Percutaneous system for dynamic spinal stabilization
US9526620B2 (en) 2009-03-30 2016-12-27 DePuy Synthes Products, Inc. Zero profile spinal fusion cage
US9532881B2 (en) 2012-08-12 2017-01-03 Brian Albert Hauck Memory material implant system and methods of use
US9532883B2 (en) 2012-04-13 2017-01-03 Neuropro Technologies, Inc. Bone fusion device
WO2017003461A1 (en) * 2015-06-30 2017-01-05 University Of South Florida Osteoconductive and osteoinductive implant for augmentation, stabilization, or defect reconstruction
US9545321B2 (en) 2013-03-14 2017-01-17 Spinal Stabilization Technologies Llc Prosthetic spinal disk nucleus
US9561117B2 (en) 2012-07-26 2017-02-07 DePuy Synthes Products, Inc. Expandable implant
US20170035542A1 (en) * 2010-10-06 2017-02-09 Astora Women's Health, Llc Implants with absorbalble and non-absorbable features for the treatment of female pelvic conditions
US9572676B2 (en) 2013-03-14 2017-02-21 DePuy Synthes Products, Inc. Adjustable multi-volume balloon for spinal interventions
US9585764B2 (en) * 2012-07-26 2017-03-07 Warsaw Orthopedic, Inc. Bone implant device
US9585761B2 (en) 2013-03-14 2017-03-07 DePuy Synthes Products, Inc. Angulated rings and bonded foils for use with balloons for fusion and dynamic stabilization
US9592258B2 (en) 2003-06-27 2017-03-14 DePuy Synthes Products, Inc. Treatment of neurological injury by administration of human umbilical cord tissue-derived cells
US9592132B2 (en) 2015-01-09 2017-03-14 Shape Memory Orthopedics Shape-memory spinal fusion system
US20170112959A1 (en) * 2015-10-12 2017-04-27 Erik Erbe Novel osteogenic and angiogenic implant material
US9636235B2 (en) 2012-09-13 2017-05-02 H & M Innovations, Llc Bone infusion apparatus and methods for interbody grafts
US9642932B2 (en) 2006-09-14 2017-05-09 DePuy Synthes Products, Inc. Bone cement and methods of use thereof
US9668875B2 (en) 1999-03-07 2017-06-06 Nuvasive, Inc. Method and apparatus for computerized surgery
US9687281B2 (en) 2012-12-20 2017-06-27 Illuminoss Medical, Inc. Distal tip for bone fixation devices
US9717601B2 (en) 2013-02-28 2017-08-01 DePuy Synthes Products, Inc. Expandable intervertebral implant, system, kit and method
US9750552B2 (en) 2009-07-06 2017-09-05 DePuy Synthes Products, Inc. Expandable fixation assemblies
US9775712B2 (en) 2015-06-30 2017-10-03 University Of South Florida Osteoconductive and osteoinductive implant for augmentation, stabilization, or defect reconstruction
US9801725B2 (en) 2009-12-09 2017-10-31 DePuy Synthes Products, Inc. Aspirating implants and method of bony regeneration
CN107335127A (en) * 2016-04-28 2017-11-10 美敦力心血管股份有限公司 The method of medical treatment device and the balloon-expandable for covering medical treatment device
US9833334B2 (en) 2010-06-24 2017-12-05 DePuy Synthes Products, Inc. Enhanced cage insertion assembly
US9878133B2 (en) 2006-08-07 2018-01-30 W. L. Gore & Associates, Inc. Inflatable imbibed polymer devices
US9901457B2 (en) 2014-10-16 2018-02-27 Jmea Corporation Coiling implantable prostheses
US9913727B2 (en) 2015-07-02 2018-03-13 Medos International Sarl Expandable implant
US9918767B2 (en) 2005-08-01 2018-03-20 DePuy Synthes Products, Inc. Temperature control system
US9931348B2 (en) 2011-07-06 2018-04-03 Rutgers, The State University Of New Jersey Vanadium compounds as therapeutic adjuncts for cartilage injury and repair
US9974665B2 (en) 2004-11-03 2018-05-22 Neuropro Technologies, Inc. Bone fusion device
US9987052B2 (en) 2015-02-24 2018-06-05 X-Spine Systems, Inc. Modular interspinous fixation system with threaded component
US9993349B2 (en) 2002-06-27 2018-06-12 DePuy Synthes Products, Inc. Intervertebral disc
US10028776B2 (en) 2010-10-20 2018-07-24 206 Ortho, Inc. Method and apparatus for treating bone fractures, and/or for fortifying and/or augmenting bone, including the provision and use of composite implants
US10034768B2 (en) * 2015-09-02 2018-07-31 Globus Medical, Inc. Implantable systems, devices and related methods
US20180235776A1 (en) * 2009-12-07 2018-08-23 Samy Abdou Devices and methods for minimally invasive spinal stablization and instrumentation
US10085783B2 (en) 2013-03-14 2018-10-02 Izi Medical Products, Llc Devices and methods for treating bone tissue
US10098757B2 (en) 2013-03-15 2018-10-16 Neuropro Technologies Inc. Bodiless bone fusion device, apparatus and method
US10111760B2 (en) 2017-01-18 2018-10-30 Neuropro Technologies, Inc. Bone fusion system, device and method including a measuring mechanism
US10130736B1 (en) 2010-05-14 2018-11-20 Musculoskeletal Transplant Foundation Tissue-derived tissuegenic implants, and methods of fabricating and using same
US10143560B2 (en) 2006-06-08 2018-12-04 Francis Pflum Sac for use in spinal surgery
US10159583B2 (en) 2012-04-13 2018-12-25 Neuropro Technologies, Inc. Bone fusion device
US10159582B2 (en) 2011-09-16 2018-12-25 DePuy Synthes Products, Inc. Removable, bone-securing cover plate for intervertebral fusion cage
WO2018237368A1 (en) * 2017-06-23 2018-12-27 New York Society For The Ruptured And Crippled Maintaining The Hospital For Special Surgery Composition, uses, and methods of treating spinal disc degeneration through sonic hedgehog signaling pathway
US10167447B2 (en) 2012-12-21 2019-01-01 Zimmer, Inc. Supports and methods for promoting integration of cartilage tissue explants
US10179834B2 (en) 2013-04-10 2019-01-15 The University Of Melbourne Biodegradable network polymers for regenerative medicine and tissue engineering
US10213321B2 (en) 2017-01-18 2019-02-26 Neuropro Technologies, Inc. Bone fusion system, device and method including delivery apparatus
US10292830B2 (en) 2011-08-09 2019-05-21 Neuropro Technologies, Inc. Bone fusion device, system and method
US10369015B2 (en) 2010-09-23 2019-08-06 DePuy Synthes Products, Inc. Implant inserter having a laterally-extending dovetail engagement feature
US10390963B2 (en) 2006-12-07 2019-08-27 DePuy Synthes Products, Inc. Intervertebral implant
US10398563B2 (en) 2017-05-08 2019-09-03 Medos International Sarl Expandable cage
US10420654B2 (en) 2011-08-09 2019-09-24 Neuropro Technologies, Inc. Bone fusion device, system and method
US10433974B2 (en) 2003-06-30 2019-10-08 DePuy Synthes Products, Inc. Intervertebral implant with conformable endplate
US10463380B2 (en) 2016-12-09 2019-11-05 Dfine, Inc. Medical devices for treating hard tissues and related methods
US10478241B2 (en) 2016-10-27 2019-11-19 Merit Medical Systems, Inc. Articulating osteotome with cement delivery channel
US10507265B2 (en) 2006-05-08 2019-12-17 Nuvasive, Inc. Cancellous bone product including viable osteogenic cells
US10525169B2 (en) 2010-10-20 2020-01-07 206 Ortho, Inc. Method and apparatus for treating bone fractures, and/or for fortifying and/or augmenting bone, including the provision and use of composite implants, and novel composite structures which may be used for medical and non-medical applications
US10525168B2 (en) 2010-10-20 2020-01-07 206 Ortho, Inc. Method and apparatus for treating bone fractures, and/or for fortifying and/or augmenting bone, including the provision and use of composite implants, and novel composite structures which may be used for medical and non-medical applications
US10531957B2 (en) 2015-05-21 2020-01-14 Musculoskeletal Transplant Foundation Modified demineralized cortical bone fibers
US10537436B2 (en) 2016-11-01 2020-01-21 DePuy Synthes Products, Inc. Curved expandable cage
US10548740B1 (en) 2016-10-25 2020-02-04 Samy Abdou Devices and methods for vertebral bone realignment
US10575961B1 (en) 2011-09-23 2020-03-03 Samy Abdou Spinal fixation devices and methods of use
US10575967B2 (en) 2015-09-01 2020-03-03 Spinal Stabilization Technologies Llc Implantable nuclear prosthesis
US10624652B2 (en) 2010-04-29 2020-04-21 Dfine, Inc. System for use in treatment of vertebral fractures
US10660656B2 (en) 2017-01-06 2020-05-26 Dfine, Inc. Osteotome with a distal portion for simultaneous advancement and articulation
US10695105B2 (en) 2012-08-28 2020-06-30 Samy Abdou Spinal fixation devices and methods of use
US20200237356A1 (en) * 2019-01-30 2020-07-30 Ethicon, Inc. Surgical Delivery Devices for Meltable Bone Wax or Bone Putty
US10729560B2 (en) 2017-01-18 2020-08-04 Neuropro Technologies, Inc. Bone fusion system, device and method including an insertion instrument
US10780197B1 (en) * 2012-10-29 2020-09-22 Nuvasive, Inc. Malleable, cryopreserved osteogenic compositions with viable cells
US20200306052A1 (en) * 2019-03-29 2020-10-01 Medos International Sarl Inflatable non-distracting intervertebral implants and related methods
CN111759532A (en) * 2020-07-07 2020-10-13 复旦大学附属华山医院 Do not rely on sacculus under shoulder peak of cyst wall leakproofness for long-term use
US10806593B2 (en) * 2013-06-24 2020-10-20 DePuy Synthes Products, Inc. Cortical rim-supporting interbody device
US10857261B2 (en) 2010-10-20 2020-12-08 206 Ortho, Inc. Implantable polymer for bone and vascular lesions
US10857003B1 (en) 2015-10-14 2020-12-08 Samy Abdou Devices and methods for vertebral stabilization
US10888433B2 (en) 2016-12-14 2021-01-12 DePuy Synthes Products, Inc. Intervertebral implant inserter and related methods
US10918498B2 (en) 2004-11-24 2021-02-16 Samy Abdou Devices and methods for inter-vertebral orthopedic device placement
US10940016B2 (en) 2017-07-05 2021-03-09 Medos International Sarl Expandable intervertebral fusion cage
US10973657B2 (en) 2017-01-18 2021-04-13 Neuropro Technologies, Inc. Bone fusion surgical system and method
US10973648B1 (en) 2016-10-25 2021-04-13 Samy Abdou Devices and methods for vertebral bone realignment
US11006982B2 (en) 2012-02-22 2021-05-18 Samy Abdou Spinous process fixation devices and methods of use
US11020237B2 (en) 2006-12-22 2021-06-01 Medos International Sarl Composite vertebral spacers and instrument
US11026744B2 (en) 2016-11-28 2021-06-08 Dfine, Inc. Tumor ablation devices and related methods
US11058796B2 (en) 2010-10-20 2021-07-13 206 Ortho, Inc. Method and apparatus for treating bone fractures, and/or for fortifying and/or augmenting bone, including the provision and use of composite implants, and novel composite structures which may be used for medical and non-medical applications
US11071572B2 (en) 2018-06-27 2021-07-27 Illuminoss Medical, Inc. Systems and methods for bone stabilization and fixation
US11090092B2 (en) 2009-12-07 2021-08-17 Globus Medical Inc. Methods and apparatus for treating vertebral fractures
US11141206B2 (en) * 2016-06-30 2021-10-12 Teknimed Bone substitute and independent injection system
WO2021205357A1 (en) 2020-04-07 2021-10-14 Ethicon, Inc. Cortical rim-supporting interbody device
US11173040B2 (en) 2012-10-22 2021-11-16 Cogent Spine, LLC Devices and methods for spinal stabilization and instrumentation
US11179248B2 (en) 2018-10-02 2021-11-23 Samy Abdou Devices and methods for spinal implantation
US11197681B2 (en) 2009-05-20 2021-12-14 Merit Medical Systems, Inc. Steerable curvable vertebroplasty drill
US11207109B2 (en) 2010-10-20 2021-12-28 206 Ortho, Inc. Method and apparatus for treating bone fractures, and/or for fortifying and/or augmenting bone, including the provision and use of composite implants, and novel composite structures which may be used for medical and non-medical applications
US11224453B2 (en) 2014-07-08 2022-01-18 Spinal Elements, Inc. Apparatus and methods for disrupting intervertebral disc tissue
US11291483B2 (en) 2010-10-20 2022-04-05 206 Ortho, Inc. Method and apparatus for treating bone fractures, and/or for fortifying and/or augmenting bone, including the provision and use of composite implants
US11305035B2 (en) 2010-05-14 2022-04-19 Musculoskeletal Transplant Foundatiaon Tissue-derived tissuegenic implants, and methods of fabricating and using same
US20220142692A1 (en) * 2006-05-03 2022-05-12 P Tech, Llc Methods and Devices for Utilizing Bondable Materials
US11344424B2 (en) 2017-06-14 2022-05-31 Medos International Sarl Expandable intervertebral implant and related methods
US11426286B2 (en) 2020-03-06 2022-08-30 Eit Emerging Implant Technologies Gmbh Expandable intervertebral implant
US11426290B2 (en) 2015-03-06 2022-08-30 DePuy Synthes Products, Inc. Expandable intervertebral implant, system, kit and method
US11446156B2 (en) 2018-10-25 2022-09-20 Medos International Sarl Expandable intervertebral implant, inserter instrument, and related methods
US11452607B2 (en) 2010-10-11 2022-09-27 DePuy Synthes Products, Inc. Expandable interspinous process spacer implant
US11471145B2 (en) 2018-03-16 2022-10-18 Spinal Elements, Inc. Articulated instrumentation and methods of using the same
US11484627B2 (en) 2010-10-20 2022-11-01 206 Ortho, Inc. Method and apparatus for treating bone fractures, and/or for fortifying and/or augmenting bone, including the provision and use of composite implants, and novel composite structures which may be used for medical and non-medical applications
US11497616B2 (en) 2012-11-09 2022-11-15 DePuy Synthes Products, Inc. Interbody device with opening to allow packing graft and other biologics
US11497619B2 (en) 2013-03-07 2022-11-15 DePuy Synthes Products, Inc. Intervertebral implant
US11510788B2 (en) 2016-06-28 2022-11-29 Eit Emerging Implant Technologies Gmbh Expandable, angularly adjustable intervertebral cages
US11510723B2 (en) 2018-11-08 2022-11-29 Dfine, Inc. Tumor ablation device and related systems and methods
US11529241B2 (en) 2010-09-23 2022-12-20 DePuy Synthes Products, Inc. Fusion cage with in-line single piece fixation
US11554020B2 (en) 2020-09-08 2023-01-17 Life Spine, Inc. Expandable implant with pivoting control assembly
US11564811B2 (en) 2015-02-06 2023-01-31 Spinal Elements, Inc. Graft material injector system and method
US11583327B2 (en) 2018-01-29 2023-02-21 Spinal Elements, Inc. Minimally invasive interbody fusion
US11596522B2 (en) 2016-06-28 2023-03-07 Eit Emerging Implant Technologies Gmbh Expandable and angularly adjustable intervertebral cages with articulating joint
US11602439B2 (en) 2020-04-16 2023-03-14 Life Spine, Inc. Expandable implant assembly
US11633287B2 (en) 2014-11-04 2023-04-25 Spinal Stabilization Technologies Llc Percutaneous implantable nuclear prosthesis
US11638649B2 (en) 2014-11-04 2023-05-02 Spinal Stabilization Technologies Llc Percutaneous implantable nuclear prosthesis
US11678996B2 (en) 2010-09-23 2023-06-20 DePuy Synthes Products, Inc. Stand alone intervertebral fusion device
US11744710B2 (en) 2018-09-04 2023-09-05 Spinal Stabilization Technologies Llc Implantable nuclear prosthesis, kits, and related methods
US11752009B2 (en) 2021-04-06 2023-09-12 Medos International Sarl Expandable intervertebral fusion cage
US11771483B2 (en) 2017-03-22 2023-10-03 Spinal Elements, Inc. Minimal impact access system to disc space
US11844702B2 (en) 2012-03-06 2023-12-19 DePuy Synthes Products, Inc. Nubbed plate
US11850160B2 (en) 2021-03-26 2023-12-26 Medos International Sarl Expandable lordotic intervertebral fusion cage
US11857432B2 (en) 2020-04-13 2024-01-02 Life Spine, Inc. Expandable implant assembly
US11883303B2 (en) 2019-12-30 2024-01-30 Vertebration, Inc. Spine surgery method and instrumentation
US11896494B2 (en) 2017-07-10 2024-02-13 Life Spine, Inc. Expandable implant assembly
US11911287B2 (en) 2010-06-24 2024-02-27 DePuy Synthes Products, Inc. Lateral spondylolisthesis reduction cage
US11918483B2 (en) 2021-11-15 2024-03-05 Cogent Spine Llc Devices and methods for spinal stabilization and instrumentation

Families Citing this family (95)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
TW200400062A (en) 2002-04-03 2004-01-01 Mathys Medizinaltechnik Ag Kneadable, pliable bone replacement material
US7744651B2 (en) 2002-09-18 2010-06-29 Warsaw Orthopedic, Inc Compositions and methods for treating intervertebral discs with collagen-based materials
US20040054414A1 (en) 2002-09-18 2004-03-18 Trieu Hai H. Collagen-based materials and methods for augmenting intervertebral discs
CN100394989C (en) 2002-11-15 2008-06-18 华沙整形外科股份有限公司 Collagen-based materials and methods for augmenting intervertebral discs
DE502004010737D1 (en) 2003-12-09 2010-03-25 Biedermann Motech Gmbh Height-adjustable intervertebral implant
DE602005023583D1 (en) 2004-02-09 2010-10-28 Depuy Spine Inc SYSTEMS FOR SPINE SURGERY SURGERY
US8636802B2 (en) 2004-03-06 2014-01-28 DePuy Synthes Products, LLC Dynamized interspinal implant
EP1604693A1 (en) * 2004-06-09 2005-12-14 Scil Technology GmbH In situ forming scaffold, its manufacturing and use
FR2874814B1 (en) * 2004-09-08 2007-11-16 Hassan Razian INTERVERTEBRAL CAGE
US7473678B2 (en) 2004-10-14 2009-01-06 Biomimetic Therapeutics, Inc. Platelet-derived growth factor compositions and methods of use thereof
US7427295B2 (en) * 2005-02-03 2008-09-23 Elli Quence, Llc Spinal fill for disk surgery
JP2008531123A (en) * 2005-02-25 2008-08-14 ジンテス ゲゼルシャフト ミット ベシュレンクテル ハフツング Resorbable containment device and its manufacturing and use processes
US8092528B2 (en) 2005-05-27 2012-01-10 Depuy Spine, Inc. Intervertebral ligament having a helical bone fastener
US7628800B2 (en) * 2005-06-03 2009-12-08 Warsaw Orthopedic, Inc. Formed in place corpectomy device
US7601172B2 (en) * 2005-06-15 2009-10-13 Ouroboros Medical, Inc. Mechanical apparatus and method for artificial disc replacement
WO2007053850A2 (en) 2005-11-01 2007-05-10 Osteotech, Inc. Bone matrix compositions and methods
EP1951327A2 (en) 2005-11-17 2008-08-06 Biomimetic Therapeutics, Inc. Maxillofacial bone augmentation using rhpdgf-bb and a biocompatible matrix
EP1960008A2 (en) * 2005-12-14 2008-08-27 Scil Technology GmbH A moldable biomaterial for bone regeneration
CA2641860C (en) 2006-02-09 2015-07-14 Biomimetic Therapeutics, Inc. Compositions and methods for treating bone
US8133279B2 (en) 2006-04-27 2012-03-13 Warsaw Orthopedic, Inc. Methods for treating an annulus defect of an intervertebral disc
US20070255406A1 (en) 2006-04-27 2007-11-01 Sdgi Holdings, Inc. Devices, apparatus, and methods for bilateral approach to disc augmentation
EP2015710A1 (en) 2006-05-11 2009-01-21 Columna Pty Ltd Implanting a tissue prosthesis
CN100428964C (en) * 2006-06-29 2008-10-29 武汉理工大学 Composite material of RGD polypeptide grafted poly (hydroxyacetic acid-L- lysine-L- lactic acid) / beta tricalcium phosphate, and preparation method
US8118779B2 (en) 2006-06-30 2012-02-21 Warsaw Orthopedic, Inc. Collagen delivery device
US8399619B2 (en) 2006-06-30 2013-03-19 Warsaw Orthopedic, Inc. Injectable collagen material
US9161967B2 (en) 2006-06-30 2015-10-20 Biomimetic Therapeutics, Llc Compositions and methods for treating the vertebral column
US9642891B2 (en) 2006-06-30 2017-05-09 Biomimetic Therapeutics, Llc Compositions and methods for treating rotator cuff injuries
JP5268113B2 (en) * 2006-09-20 2013-08-21 ウッドウェルディング・アクチェンゲゼルシャフト Device to be implanted in human or animal tissue and method for embedding and assembling the device
EP2462895B1 (en) 2006-11-03 2016-11-02 BioMimetic Therapeutics, LLC Compositions and methods for arthrodetic procedures
EP3628275B1 (en) * 2007-04-17 2023-03-01 The Board of Trustees of the Leland Stanford Junior University Hydrogel arthroplasty device
US8273124B2 (en) 2007-05-17 2012-09-25 Depuy Spine, Inc. Self-distracting cage
WO2008157495A2 (en) 2007-06-15 2008-12-24 Osteotech, Inc. Bone matrix compositions and methods
US9554920B2 (en) 2007-06-15 2017-01-31 Warsaw Orthopedic, Inc. Bone matrix compositions having nanoscale textured surfaces
US9358113B2 (en) 2007-07-10 2016-06-07 Warsaw Orthopedic, Inc. Delivery system
US20090054934A1 (en) * 2007-07-25 2009-02-26 Depuy Spine, Inc. Expandable fillers for bone cement
KR100906545B1 (en) * 2007-08-08 2009-07-07 퍼저 파마수티컬 컴퍼니 리미티드 Bio-degenerable bone cement and manufacturing method thereof
WO2009100454A1 (en) * 2008-02-07 2009-08-13 Biomimetic Therapeutics, Inc. Compositions and methods for distraction osteogenesis
EP2254649B1 (en) * 2008-03-28 2018-03-28 Warsaw Orthopedic, Inc. Delivery system attachment
KR101464983B1 (en) * 2008-05-01 2014-11-25 스파인셀 프러프라이어테리 리미티드 System methods and apparatuses for formation and insertion of tissue prothesis
US20120209396A1 (en) 2008-07-07 2012-08-16 David Myung Orthopedic implants having gradient polymer alloys
US8497023B2 (en) 2008-08-05 2013-07-30 Biomimedica, Inc. Polyurethane-grafted hydrogels
MX2011002555A (en) 2008-09-09 2011-08-03 Biomimetic Therapeutics Inc Platelet-derived growth factor compositions and methods for the treatment of tendon and ligament injuries.
EP2339985A4 (en) * 2008-09-12 2013-07-03 Articulinx Inc Tether-based orthopedic joint device delivery methods
US9011537B2 (en) 2009-02-12 2015-04-21 Warsaw Orthopedic, Inc. Delivery system cartridge
WO2010115138A2 (en) * 2009-04-03 2010-10-07 Light Cure, Llc Devices and injectable or implantable compositions for intervertebral fusion
US9028553B2 (en) 2009-11-05 2015-05-12 DePuy Synthes Products, Inc. Self-pivoting spinal implant and associated instrumentation
US8492335B2 (en) 2010-02-22 2013-07-23 Biomimetic Therapeutics, Llc Platelet-derived growth factor compositions and methods for the treatment of tendinopathies
EP2368955A1 (en) 2010-03-26 2011-09-28 Sika Technology AG Shape memory material on the basis of a structural adhesive
EP2368956A1 (en) 2010-03-26 2011-09-28 Sika Technology AG Shape memory material on the basis of a structural adhesive
CN101954146B (en) * 2010-10-20 2012-05-23 陈柏龄 Double-balloon dilator for bone surgery
KR20180121674A (en) * 2010-12-13 2018-11-07 바이오미메틱 세라퓨틱스, 엘엘씨 Compositions and methods for spine fusion procedures
WO2012129197A1 (en) 2011-03-22 2012-09-27 Depuy Spine, Inc. Universal trial for lateral cages
US9198765B1 (en) 2011-10-31 2015-12-01 Nuvasive, Inc. Expandable spinal fusion implants and related methods
KR20150023455A (en) 2012-05-29 2015-03-05 엔엘티 스파인 리미티드. Laterally deflectable implant
WO2014018802A1 (en) * 2012-07-25 2014-01-30 Spineology, Inc. Mesh spacer hybrid
CN103830775B (en) * 2012-11-27 2017-05-17 北京奥精医药科技有限公司 High-strength collagen base artificial bone repair material
US8663332B1 (en) 2012-12-13 2014-03-04 Ouroboros Medical, Inc. Bone graft distribution system
US10022245B2 (en) 2012-12-17 2018-07-17 DePuy Synthes Products, Inc. Polyaxial articulating instrument
CN103126788B (en) * 2013-02-28 2016-04-20 李开南 Absorbable lumbar facet joint fusion cage
US9186259B2 (en) 2013-09-09 2015-11-17 Ouroboros Medical, Inc. Expandable trials
CN103655010B (en) * 2013-11-20 2016-04-27 苏州博习医疗科技有限公司 Intervertebral fills fusing device
EP3076902A4 (en) * 2013-12-03 2017-08-16 Cornell University Method of repairing an annulus and collagen gel composition
CN104707172B (en) * 2013-12-12 2017-03-29 中国科学院深圳先进技术研究院 A kind of artificial intervertebral disk and preparation method thereof
US9757245B2 (en) * 2014-04-24 2017-09-12 DePuy Synthes Products, Inc. Patient-specific spinal fusion cage and methods of making same
US9060876B1 (en) 2015-01-20 2015-06-23 Ouroboros Medical, Inc. Stabilized intervertebral scaffolding systems
US11077228B2 (en) 2015-08-10 2021-08-03 Hyalex Orthopaedics, Inc. Interpenetrating polymer networks
US9486323B1 (en) * 2015-11-06 2016-11-08 Spinal Stabilization Technologies Llc Nuclear implant apparatus and method following partial nuclectomy
US10493247B2 (en) * 2016-03-15 2019-12-03 Medtronic Holding Company Sàrl Devices for delivering a chemical denervation agent and methods of use
US9883953B1 (en) 2016-09-21 2018-02-06 Integrity Implants Inc. Stabilized laterovertically-expanding fusion cage systems with tensioner
ES2672265B1 (en) 2016-11-07 2019-04-10 Inst Biomecanico De Barcelona S L DEVICE FOR INTERVERTEBRAL FUSION COMPRISING AN INTERVERTEBRAL STABILIZATION SCREW AND A COMPOSITION FOR BONE REMODELING
WO2018132502A1 (en) 2017-01-10 2018-07-19 Anza Innovations Inc. Expandable intervertebral fusion device
US11213402B2 (en) 2017-01-11 2022-01-04 Loubert S. Suddaby Endoscopically implantable inflatable interbody fusion device
CN107212919A (en) * 2017-06-22 2017-09-29 苏州博习医疗科技有限公司 Intervertebral shapes fusing device and application method
USD816844S1 (en) 2017-06-29 2018-05-01 American Medical Ortho Systems LLC Lumbar interbody implant
US10966843B2 (en) 2017-07-18 2021-04-06 DePuy Synthes Products, Inc. Implant inserters and related methods
WO2019023251A1 (en) 2017-07-24 2019-01-31 Integrity Implants, Inc. Surgical implant and related methods
US11045331B2 (en) 2017-08-14 2021-06-29 DePuy Synthes Products, Inc. Intervertebral implant inserters and related methods
USD841167S1 (en) 2017-08-16 2019-02-19 American Medical Ortho Systems LLC Lumbar interbody implant
US10709578B2 (en) 2017-08-25 2020-07-14 Integrity Implants Inc. Surgical biologics delivery system and related methods
CN107698860B (en) * 2017-10-30 2020-09-08 美瑞新材料股份有限公司 High-resilience composition foaming material for soles and preparation method thereof
CN108309517B (en) * 2018-01-25 2019-08-30 中国人民解放军新疆军区总医院 A kind of absorbable cervical fusion cage and preparation method thereof
US11285018B2 (en) 2018-03-01 2022-03-29 Integrity Implants Inc. Expandable fusion device with independent expansion systems
US10869950B2 (en) 2018-07-17 2020-12-22 Hyalex Orthopaedics, Inc. Ionic polymer compositions
DE102018128822A1 (en) 2018-11-16 2020-05-20 Albert-Ludwigs-Universität Freiburg RIBOFLAVIN FOR THE TREATMENT OF COLLAGEN-TISSUE TISSUES FOR DISEASES OF JOINTS, IN PARTICULAR THE DISC
CN109998518B (en) * 2019-03-05 2020-08-07 深圳先进技术研究院 Diaphragm movement auxiliary device and diaphragm movement auxiliary system
CN110354298B (en) * 2019-07-26 2021-08-17 南京聚屹新材料有限公司 Preparation method of in-situ crosslinked silver nanowire/polycaprolactone surgical suture
EP3791831A1 (en) * 2019-09-10 2021-03-17 AIT Austrian Institute of Technology GmbH Implant for treatment of a hernia
US20230158210A1 (en) * 2019-11-01 2023-05-25 Icahn School Of Medicine At Mount Sinai Iimproved approach to repair tissue defects by bonding injectable gels to native soft tissues
CN111096829A (en) * 2020-01-09 2020-05-05 哈尔滨工业大学 Shape memory polymer interbody fusion cage
CN111110406A (en) * 2020-01-09 2020-05-08 哈尔滨工业大学 Shape memory negative poisson ratio intervertebral fusion cage
CN112716664B (en) * 2021-04-06 2021-06-22 珠海维尔康生物科技有限公司 Fence type bone cement spine fusion device adopting balloon forming
US11801143B2 (en) 2021-07-01 2023-10-31 Hyalex Orthopaedics, Inc. Multi-layered biomimetic osteochondral implants and methods of using thereof
CN113351023B (en) * 2021-07-07 2023-04-21 内蒙古立威生物科技有限公司 MBR (Membrane biological reactor) membrane offline cleaning and repairing method for sewage treatment workshop
CN114470324B (en) * 2022-02-08 2023-04-04 福建医科大学附属协和医院 Novel strategy for the modification of universal bone implants for the intervention of bone defects associated with diabetes
WO2023177179A1 (en) * 2022-03-15 2023-09-21 가톨릭관동대학교산학협력단 Loop-transformable expandable cage

Citations (84)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2115250A (en) * 1936-05-28 1938-04-26 Rohm & Haas Organic nitrogen bases and their salts
US2170111A (en) * 1936-05-28 1939-08-22 Rohm & Haas Manufacture of amines
US2229024A (en) * 1939-05-23 1941-01-21 Rohm & Haas Aromatic ether of polyalkoxyalkylalkylene polyamines and process for obtaining them
US2706701A (en) * 1952-04-15 1955-04-19 Gen Aniline & Film Corp Process for the preparation of iodinepolyvinylpyrrolidone by dry mixing
US2710277A (en) * 1952-04-23 1955-06-07 West Laboratories Inc Iodine phosphate ester compositions
US2826532A (en) * 1952-04-15 1958-03-11 Gen Aniline & Film Corp Process of stabilizing polyvinyl pyrrolidone-iodine compositions
US2900305A (en) * 1952-04-15 1959-08-18 Gen Aniline & Film Corp Preparation of iodine polyvinylpyrrolidone adducts
US2977315A (en) * 1956-09-12 1961-03-28 Lazarus Lab Inc Water soluble iodine-phosphoric-acidsynthetic detergent composition
US3228828A (en) * 1963-02-15 1966-01-11 Standard Naphthalene Products Insecticide composition comprising naphthalene and paraffinic hydrocarbon
US3717655A (en) * 1968-08-19 1973-02-20 Janssen Pharmaceutica Nv 1-(beta-aryl)ethyl-imidazole derivatives
US3936466A (en) * 1974-04-01 1976-02-03 Interx Research Corporation 3-Chloro-tetrahydro-1,3-oxazines or oxazolidines spiro substituted
US4352883A (en) * 1979-03-28 1982-10-05 Damon Corporation Encapsulation of biological material
US4440921A (en) * 1982-06-21 1984-04-03 Research Corporation Coupling of polyorganophosphazenes to carboxylic acid
US4495174A (en) * 1982-06-21 1985-01-22 Research Corporation Anesthetic polyorganophosphazenes
US4645503A (en) * 1985-08-27 1987-02-24 Orthomatrix Inc. Moldable bone-implant material
US4686607A (en) * 1986-01-08 1987-08-11 Teradyne, Inc. Daughter board/backplane assembly
US4743256A (en) * 1985-10-04 1988-05-10 Brantigan John W Surgical prosthetic implant facilitating vertebral interbody fusion and method
US4772287A (en) * 1987-08-20 1988-09-20 Cedar Surgical, Inc. Prosthetic disc and method of implanting
US4880622A (en) * 1986-05-20 1989-11-14 Research Corporation Technologies, Inc. Water-soluble phosphazene polymers having pharmacological applications
US4943245A (en) * 1989-07-31 1990-07-24 Microdot Inc. Coaxial electrical connector
US4964814A (en) * 1986-10-03 1990-10-23 Minnesota Mining And Manufacturing Co. Shielded and grounded connector system for coaxial cables
US5133755A (en) * 1986-01-28 1992-07-28 Thm Biomedical, Inc. Method and apparatus for diodegradable, osteogenic, bone graft substitute device
US5176538A (en) * 1991-12-13 1993-01-05 W. L. Gore & Associates, Inc. Signal interconnector module and assembly thereof
US5192327A (en) * 1991-03-22 1993-03-09 Brantigan John W Surgical prosthetic implant for vertebrae
US5397364A (en) * 1993-10-12 1995-03-14 Danek Medical, Inc. Anterior interbody fusion device
US5410016A (en) * 1990-10-15 1995-04-25 Board Of Regents, The University Of Texas System Photopolymerizable biodegradable hydrogels as tissue contacting materials and controlled-release carriers
US5441424A (en) * 1993-04-15 1995-08-15 Framatome Connectors International Connector for coaxial and/or twinaxial cables
US5443514A (en) * 1993-10-01 1995-08-22 Acromed Corporation Method for using spinal implants
US5522895A (en) * 1993-07-23 1996-06-04 Rice University Biodegradable bone templates
US5549679A (en) * 1994-05-20 1996-08-27 Kuslich; Stephen D. Expandable fabric implant for stabilizing the spinal motion segment
US5562736A (en) * 1994-10-17 1996-10-08 Raymedica, Inc. Method for surgical implantation of a prosthetic spinal disc nucleus
US5679723A (en) * 1994-11-30 1997-10-21 Ethicon, Inc. Hard tissue bone cements and substitutes
US5702449A (en) * 1995-06-07 1997-12-30 Danek Medical, Inc. Reinforced porous spinal implants
US5766036A (en) * 1996-10-11 1998-06-16 Molex Incorporated Impedance matched cable assembly having latching subassembly
US5775924A (en) * 1996-10-11 1998-07-07 Molex Incorporated Modular terminating connector with frame ground
US5775947A (en) * 1993-07-27 1998-07-07 Japan Aviation Electronics Industry, Limited Multi-contact connector with cross-talk blocking elements between signal contacts
US5800549A (en) * 1997-04-30 1998-09-01 Howmedica Inc. Method and apparatus for injecting an elastic spinal implant
US5807327A (en) * 1995-12-08 1998-09-15 Ethicon, Inc. Catheter assembly
US5824084A (en) * 1996-07-03 1998-10-20 The Cleveland Clinic Foundation Method of preparing a composite bone graft
US5833657A (en) * 1995-05-30 1998-11-10 Ethicon, Inc. Single-walled balloon catheter with non-linear compliance characteristic
US5837752A (en) * 1997-07-17 1998-11-17 Massachusetts Institute Of Technology Semi-interpenetrating polymer networks
US5888220A (en) * 1994-05-06 1999-03-30 Advanced Bio Surfaces, Inc. Articulating joint repair
US5888227A (en) * 1995-10-20 1999-03-30 Synthes (U.S.A.) Inter-vertebral implant
US5972385A (en) * 1997-01-15 1999-10-26 Orquest, Inc. Collagen-polysaccharide matrix for bone and cartilage repair
US5971770A (en) * 1997-11-05 1999-10-26 Labinal Components And Systems, Inc. Coaxial connector with bellows spring portion or raised bump
US6071982A (en) * 1997-04-18 2000-06-06 Cambridge Scientific, Inc. Bioerodible polymeric semi-interpenetrating network alloys for surgical plates and bone cements, and method for making same
US6113638A (en) * 1999-02-26 2000-09-05 Williams; Lytton A. Method and apparatus for intervertebral implant anchorage
US6113624A (en) * 1995-10-02 2000-09-05 Ethicon, Inc. Absorbable elastomeric polymer
US6123550A (en) * 1996-12-13 2000-09-26 Fuba Automotive Gmbh & Co Kg Line plug connection
US6146202A (en) * 1998-08-12 2000-11-14 Robinson Nugent, Inc. Connector apparatus
US6147135A (en) * 1998-12-31 2000-11-14 Ethicon, Inc. Fabrication of biocompatible polymeric composites
US6165486A (en) * 1998-11-19 2000-12-26 Carnegie Mellon University Biocompatible compositions and methods of using same
US6171610B1 (en) * 1998-04-24 2001-01-09 University Of Massachusetts Guided development and support of hydrogel-cell compositions
US6187048B1 (en) * 1994-05-24 2001-02-13 Surgical Dynamics, Inc. Intervertebral disc implant
US6197325B1 (en) * 1990-11-27 2001-03-06 The American National Red Cross Supplemented and unsupplemented tissue sealants, methods of their production and use
US6203565B1 (en) * 1990-06-28 2001-03-20 Peter M. Bonutti Surgical devices assembled using heat bondable materials
US6203369B1 (en) * 1999-10-25 2001-03-20 3M Innovative Properties Company High frequency cable connector having low self-inductance ground return paths
US6214368B1 (en) * 1995-05-19 2001-04-10 Etex Corporation Bone substitution material and a method of its manufacture
US6224894B1 (en) * 1995-03-06 2001-05-01 Ethicon, Inc. Copolymers of absorbable polyoxaesters
US6248131B1 (en) * 1994-05-06 2001-06-19 Advanced Bio Surfaces, Inc. Articulating joint repair
US6264695B1 (en) * 1999-09-30 2001-07-24 Replication Medical, Inc. Spinal nucleus implant
US6280474B1 (en) * 1997-01-09 2001-08-28 Neucoll, Inc. Devices for tissue repair and methods for preparation and use thereof
US6306177B1 (en) * 1994-05-06 2001-10-23 Advanced Bio Surfaces, Inc. Biomaterial system for in situ tissue repair
US20010039452A1 (en) * 1997-01-02 2001-11-08 St. Francis Medical Technologies, Inc. Spine distraction implant and method
US20010039453A1 (en) * 1997-08-13 2001-11-08 Gresser Joseph D. Resorbable interbody spinal fusion devices
US6331312B1 (en) * 1995-05-19 2001-12-18 Etex Corporation Bioresorbable ceramic composites
US6332894B1 (en) * 2000-03-07 2001-12-25 Zimmer, Inc. Polymer filled spinal fusion cage
US6368351B1 (en) * 2001-03-27 2002-04-09 Bradley J. Glenn Intervertebral space implant for use in spinal fusion procedures
US20020055781A1 (en) * 1999-12-23 2002-05-09 John A. Sazy Intervertebral cage and method of use
US20020058947A1 (en) * 2000-02-28 2002-05-16 Stephen Hochschuler Method and apparatus for treating a vertebral body
US6478624B2 (en) * 2000-06-29 2002-11-12 Robinson Nugent, Inc. High speed connector
US6494883B1 (en) * 2000-05-26 2002-12-17 Bret A. Ferree Bone reinforcers
US20020193883A1 (en) * 2001-01-25 2002-12-19 Wironen John F. Injectable porous bone graft materials
US20020198526A1 (en) * 2000-06-23 2002-12-26 Shaolian Samuel M. Formed in place fixation system with thermal acceleration
US20030028251A1 (en) * 2001-07-30 2003-02-06 Mathews Hallett H. Methods and devices for interbody spinal stabilization
US6562072B1 (en) * 1998-01-23 2003-05-13 Aesculap Ag & Co. Kg Implant for insertion between spinal column vertebrae
US6592625B2 (en) * 1999-10-20 2003-07-15 Anulex Technologies, Inc. Spinal disc annulus reconstruction method and spinal disc annulus stent
US6632235B2 (en) * 2001-04-19 2003-10-14 Synthes (U.S.A.) Inflatable device and method for reducing fractures in bone and in treating the spine
US20040049270A1 (en) * 2002-09-10 2004-03-11 Gewirtz Robert J. Bone graft device
US20040127990A1 (en) * 2002-12-31 2004-07-01 Bartish, Charles M. Novel banana cage
US6805697B1 (en) * 1999-05-07 2004-10-19 University Of Virginia Patent Foundation Method and system for fusing a spinal region
US6979352B2 (en) * 2002-11-21 2005-12-27 Depuy Acromed Methods of performing embolism-free vertebroplasty and devices therefor
US20110098818A1 (en) * 2001-05-01 2011-04-28 Brodke Darrel S Radiolucent spinal fusion cage
US20120310352A1 (en) * 2003-02-14 2012-12-06 Depuy Spine, Inc. In-situ intervertebral fusion device and method

Family Cites Families (1108)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US1965653A (en) 1932-11-01 1934-07-10 James W Kennedy Dilator
US2730159A (en) 1951-01-17 1956-01-10 Goodrich Co B F Method of making golf balls
US3091237A (en) 1960-05-16 1963-05-28 Clawson N Skinner Facial muscle and tissue conditioning device
US3112743A (en) 1960-09-01 1963-12-03 Orthopaedic Specialties Corp Method for treatment of bone fractures
DE1906284A1 (en) 1969-02-08 1970-09-03 Dr Esfandiar Shahrestani Endoprosthesis, especially for hip joints
CA962806A (en) 1970-06-04 1975-02-18 Ontario Research Foundation Surgical prosthetic device
SE391122B (en) 1971-01-25 1977-02-07 Cutter Lab PROTESTS IN THE FORM OF A SPINE BONIC DISC AND PROCEDURES FOR MANUFACTURE THEREOF
GB1430083A (en) 1972-03-08 1976-03-31 Nat Res Dev Cement fixation in the human body
US3800788A (en) 1972-07-12 1974-04-02 N White Antral catheter for reduction of fractures
US3875595A (en) 1974-04-15 1975-04-08 Edward C Froning Intervertebral disc prosthesis and instruments for locating same
US3964480A (en) 1974-10-03 1976-06-22 Froning Edward C Apparatus for sterotaxic lateral extradural disc puncture
CH624573A5 (en) 1978-02-01 1981-08-14 Sulzer Ag Intervertebral prosthesis
US4351069A (en) 1979-06-29 1982-09-28 Union Carbide Corporation Prosthetic devices having sintered thermoplastic coatings with a porosity gradient
US4274163A (en) 1979-07-16 1981-06-23 The Regents Of The University Of California Prosthetic fixation technique
US4262676A (en) 1979-08-24 1981-04-21 Khosrow Jamshidi Biopsy needle having integral stylet locking device
CA1146301A (en) 1980-06-13 1983-05-17 J. David Kuntz Intervertebral disc prosthesis
US4312337A (en) 1980-09-08 1982-01-26 Donohue Brian T Cannula and drill guide apparatus
US4313434A (en) 1980-10-17 1982-02-02 David Segal Fracture fixation
DE3142730A1 (en) 1981-04-01 1982-10-21 Curt Dipl.-Ing. 1000 Berlin Kranz "JOINT PROSTHESIS"
US4399814A (en) 1981-04-27 1983-08-23 Massachusetts Institute Of Technology Method and apparatus for pressure-coated bones
US4488549A (en) 1981-08-25 1984-12-18 University Of Exeter Pressurization of cement in bones
US4466435A (en) 1981-09-04 1984-08-21 Murray William M Bone cement nozzle and method
US4467479A (en) 1982-02-05 1984-08-28 Brody Garry S Method of surgically repairing an injured human joint and a prosthetic device therefor
US4542539A (en) 1982-03-12 1985-09-24 Artech Corp. Surgical implant having a graded porous coating
US4462394A (en) 1982-05-03 1984-07-31 Howmedica, Inc. Intramedullary canal seal for cement pressurization
US4595006A (en) 1982-08-16 1986-06-17 Burke Dennis W Apparatus for cemented implantation of prostheses
US4665906A (en) 1983-10-14 1987-05-19 Raychem Corporation Medical devices incorporating sim alloy elements
US4630616A (en) 1984-06-15 1986-12-23 Berkley And Company, Inc. Bone marrow needle
EP0176728B1 (en) 1984-09-04 1989-07-26 Humboldt-Universität zu Berlin Intervertebral-disc prosthesis
US4686973A (en) 1984-10-12 1987-08-18 Dow Corning Corporation Method of making an intramedullary bone plug and bone plug made thereby
US4697584A (en) 1984-10-12 1987-10-06 Darrel W. Haynes Device and method for plugging an intramedullary bone canal
US5030233A (en) 1984-10-17 1991-07-09 Paul Ducheyne Porous flexible metal fiber material for surgical implantation
US4628945A (en) 1985-01-25 1986-12-16 Johnson Jr Glenn W Inflatable ankle brace with porous compressible filler
US4651717A (en) 1985-04-04 1987-03-24 Dow Corning Corporation Multiple envelope tissue expander device
US4627434A (en) 1985-05-03 1986-12-09 Murray William M Bone cement system and method
US4706670A (en) 1985-11-26 1987-11-17 Meadox Surgimed A/S Dilatation catheter
US4888024A (en) 1985-11-08 1989-12-19 Powlan Roy Y Prosthetic device and method of fixation within the medullary cavity of bones
US4892550A (en) 1985-12-30 1990-01-09 Huebsch Donald L Endoprosthesis device and method
US4888022A (en) 1985-12-30 1989-12-19 Huebsch Donald L Endoprosthesis
US4714478A (en) 1986-01-17 1987-12-22 Fischer William B Prosthesis, method, and tool for installing same
US4871366A (en) 1986-05-27 1989-10-03 Clemson University Soft tissue implants for promoting tissue adhesion to same
US5051189A (en) 1989-01-31 1991-09-24 University Of Florida Method of removing an unwanted impurity from an aqueous material
GB8620937D0 (en) 1986-08-29 1986-10-08 Shepperd J A N Spinal implant
CH671691A5 (en) 1987-01-08 1989-09-29 Sulzer Ag
US4834757A (en) 1987-01-22 1989-05-30 Brantigan John W Prosthetic implant
CA1283501C (en) 1987-02-12 1991-04-30 Thomas P. Hedman Artificial spinal disc
US4838282A (en) 1987-02-26 1989-06-13 Manan Manufacturing Co., Inc. Bone biopsy needle assembly
US4714469A (en) 1987-02-26 1987-12-22 Pfizer Hospital Products Group, Inc. Spinal implant
US4941466A (en) 1987-04-13 1990-07-17 Romano Jack W Curved bore drilling method and apparatus
GB8718627D0 (en) 1987-08-06 1987-09-09 Showell A W Sugicraft Ltd Spinal implants
JPH045126Y2 (en) 1987-09-03 1992-02-14
US4870153A (en) 1987-10-22 1989-09-26 Amoco Corporation Novel poly(aryl ether) polymers
JPH01136655A (en) 1987-11-24 1989-05-29 Asahi Optical Co Ltd Movable type pyramid spacer
US4896662A (en) 1987-11-30 1990-01-30 Pfizer Hospital Products Group, Inc. Sealing device for introducing cement into a bone canal
US5282856A (en) 1987-12-22 1994-02-01 Ledergerber Walter J Implantable prosthetic device
DE3809793A1 (en) 1988-03-23 1989-10-05 Link Waldemar Gmbh Co SURGICAL INSTRUMENT SET
US4911718A (en) 1988-06-10 1990-03-27 University Of Medicine & Dentistry Of N.J. Functional and biocompatible intervertebral disc spacer
US5484437A (en) 1988-06-13 1996-01-16 Michelson; Gary K. Apparatus and method of inserting spinal implants
US6123705A (en) 1988-06-13 2000-09-26 Sdgi Holdings, Inc. Interbody spinal fusion implants
US7452359B1 (en) 1988-06-13 2008-11-18 Warsaw Orthopedic, Inc. Apparatus for inserting spinal implants
US5772661A (en) 1988-06-13 1998-06-30 Michelson; Gary Karlin Methods and instrumentation for the surgical correction of human thoracic and lumbar spinal disease from the antero-lateral aspect of the spine
US6770074B2 (en) 1988-06-13 2004-08-03 Gary Karlin Michelson Apparatus for use in inserting spinal implants
US5015247A (en) 1988-06-13 1991-05-14 Michelson Gary K Threaded spinal implant
US6923810B1 (en) 1988-06-13 2005-08-02 Gary Karlin Michelson Frusto-conical interbody spinal fusion implants
CA1333209C (en) 1988-06-28 1994-11-29 Gary Karlin Michelson Artificial spinal fusion implants
US5609635A (en) 1988-06-28 1997-03-11 Michelson; Gary K. Lordotic interbody spinal fusion implants
US5374261A (en) 1990-07-24 1994-12-20 Yoon; Inbae Multifunctional devices for use in endoscopic surgical procedures and methods-therefor
US4898577A (en) 1988-09-28 1990-02-06 Advanced Cardiovascular Systems, Inc. Guiding cathether with controllable distal tip
US4961740B1 (en) 1988-10-17 1997-01-14 Surgical Dynamics Inc V-thread fusion cage and method of fusing a bone joint
US5019083A (en) 1989-01-31 1991-05-28 Advanced Osseous Technologies, Inc. Implanting and removal of orthopedic prostheses
US4969888A (en) 1989-02-09 1990-11-13 Arie Scholten Surgical protocol for fixation of osteoporotic bone using inflatable device
CA1318469C (en) 1989-02-15 1993-06-01 Acromed Corporation Artificial disc
DE3911610A1 (en) 1989-04-08 1990-10-18 Bosch Gmbh Robert ARTIFICIAL DISC
JP2545981B2 (en) 1989-05-09 1996-10-23 東レ株式会社 Balloon catheter
US5015255A (en) 1989-05-10 1991-05-14 Spine-Tech, Inc. Spinal stabilization method
US5904690A (en) 1989-08-16 1999-05-18 Medtronic, Inc. Device or apparatus for manipulating matter
US5632746A (en) 1989-08-16 1997-05-27 Medtronic, Inc. Device or apparatus for manipulating matter
US5749879A (en) 1989-08-16 1998-05-12 Medtronic, Inc. Device or apparatus for manipulating matter
US5509923A (en) 1989-08-16 1996-04-23 Raychem Corporation Device for dissecting, grasping, or cutting an object
DE8912648U1 (en) 1989-10-23 1990-11-22 Mecron Medizinische Produkte Gmbh, 1000 Berlin, De
US5055104A (en) 1989-11-06 1991-10-08 Surgical Dynamics, Inc. Surgically implanting threaded fusion cages between adjacent low-back vertebrae by an anterior approach
US5059193A (en) 1989-11-20 1991-10-22 Spine-Tech, Inc. Expandable spinal implant and surgical method
US5152744A (en) 1990-02-07 1992-10-06 Smith & Nephew Dyonics Surgical instrument
US5147366A (en) 1990-03-01 1992-09-15 Pfizer Hospital Products Group, Inc. Pressurization of bone cement surrounding an endoprosthesis
US5331975A (en) 1990-03-02 1994-07-26 Bonutti Peter M Fluid operated retractors
US5454365A (en) 1990-11-05 1995-10-03 Bonutti; Peter M. Mechanically expandable arthroscopic retractors
US5514153A (en) 1990-03-02 1996-05-07 General Surgical Innovations, Inc. Method of dissecting tissue layers
FR2659226B1 (en) 1990-03-07 1992-05-29 Jbs Sa PROSTHESIS FOR INTERVERTEBRAL DISCS AND ITS IMPLEMENTATION INSTRUMENTS.
DE4012622C1 (en) 1990-04-20 1991-07-18 Eska Medical Luebeck Medizintechnik Gmbh & Co, 2400 Luebeck, De Two-part metal vertebra implant - has parts locked by two toothed racks, pre-stressed by elastic cushion between both implant parts
EP0453393B1 (en) 1990-04-20 1993-10-06 SULZER Medizinaltechnik AG Implant, particularly intervertebral prosthesis
US5053035A (en) 1990-05-24 1991-10-01 Mclaren Alexander C Flexible intramedullary fixation rod
US5163989A (en) 1990-08-27 1992-11-17 Advanced Cardiovascular Systems, Inc. Method for forming a balloon mold and the use of such mold
US5183052A (en) 1990-11-07 1993-02-02 Terwilliger Richard A Automatic biopsy instrument with cutting cannula
US5102413A (en) 1990-11-14 1992-04-07 Poddar Satish B Inflatable bone fixation device
US5098435A (en) 1990-11-21 1992-03-24 Alphatec Manufacturing Inc. Cannula
US5134477A (en) 1990-12-11 1992-07-28 At&T Bell Laboratories Hdtv receiver
CA2057184C (en) 1990-12-13 1996-11-19 Hisaki Abe Active carbon materials, process for the preparation thereof and the use thereof
US5071435A (en) 1990-12-20 1991-12-10 Albert Fuchs Extendible bone prosthesis
CS277533B6 (en) 1990-12-29 1993-03-17 Krajicek Milan Fixed osteaosynthesis appliance
GB2251795B (en) 1991-01-17 1995-02-08 Minnesota Mining & Mfg Orthopaedic implant
US5228441A (en) 1991-02-15 1993-07-20 Lundquist Ingemar H Torquable catheter and method
US5409453A (en) 1992-08-12 1995-04-25 Vidamed, Inc. Steerable medical probe with stylets
JPH0732841B2 (en) 1991-02-21 1995-04-12 豊田化学工業株式会社 Waste liquid treatment system for organic solvents
JP3390431B2 (en) 1991-02-22 2003-03-24 マドハヴァン、ピシャロディ Centrally expandable disc implant and method
US5123926A (en) 1991-02-22 1992-06-23 Madhavan Pisharodi Artificial spinal prosthesis
US5390683A (en) 1991-02-22 1995-02-21 Pisharodi; Madhavan Spinal implantation methods utilizing a middle expandable implant
JP3007903B2 (en) 1991-03-29 2000-02-14 京セラ株式会社 Artificial disc
US5176683A (en) 1991-04-22 1993-01-05 Kimsey Timothy P Prosthesis press and method of using the same
DK0637223T3 (en) 1991-05-29 1999-04-26 Origin Medsystems Inc Endoscopic Surgery Retention Device
US5361752A (en) 1991-05-29 1994-11-08 Origin Medsystems, Inc. Retraction apparatus and methods for endoscopic surgery
US5306307A (en) 1991-07-22 1994-04-26 Calcitek, Inc. Spinal disk implant
US5242448A (en) 1991-08-01 1993-09-07 Pettine Kenneth A Bone probe
US5329846A (en) 1991-08-12 1994-07-19 Bonutti Peter M Tissue press and system
DE4128332A1 (en) 1991-08-27 1993-03-04 Man Ceramics Gmbh SPINE BONE REPLACEMENT
US5290312A (en) 1991-09-03 1994-03-01 Alphatec Artificial vertebral body
US5285795A (en) 1991-09-12 1994-02-15 Surgical Dynamics, Inc. Percutaneous discectomy system having a bendable discectomy probe and a steerable cannula
NO924368L (en) 1991-11-22 1993-05-24 Lubrizol Corp PROCEDURE FOR THE MANUFACTURING OF SINTERED BODIES AND COMPOSITIONS USED IN THESE
US5514143A (en) 1991-11-27 1996-05-07 Apogee Medical Products, Inc. Apparatus and method for use during surgery
GB9125798D0 (en) 1991-12-04 1992-02-05 Customflex Limited Improvements in or relating to spinal vertebrae implants
US5176692A (en) 1991-12-09 1993-01-05 Wilk Peter J Method and surgical instrument for repairing hernia
US5263953A (en) 1991-12-31 1993-11-23 Spine-Tech, Inc. Apparatus and system for fusing bone joints
US5425773A (en) 1992-01-06 1995-06-20 Danek Medical, Inc. Intervertebral disk arthroplasty device
US5344252A (en) 1992-02-12 1994-09-06 Hiroshi Kakimoto Key for coupling driving and driven members together
NL9200288A (en) 1992-02-17 1993-09-16 Acromed Bv DEVICE FOR FIXING AT LEAST A PART OF THE CERVICAL AND / OR THORACAL SPIRIT COLUMN.
KR100266912B1 (en) 1992-02-28 2000-12-01 파라비 레이 Photopolymerizable biodegradable hydrogels as tissue contacting materials and controlled-release carriers
DE4208115A1 (en) 1992-03-13 1993-09-16 Link Waldemar Gmbh Co DISC ENDOPROTHESIS
DE4208116C2 (en) 1992-03-13 1995-08-03 Link Waldemar Gmbh Co Intervertebral disc prosthesis
US5171279A (en) 1992-03-17 1992-12-15 Danek Medical Method for subcutaneous suprafascial pedicular internal fixation
ATE141149T1 (en) 1992-04-21 1996-08-15 Sulzer Medizinaltechnik Ag ARTIFICIAL DISC BODY
US5306309A (en) 1992-05-04 1994-04-26 Calcitek, Inc. Spinal disk implant and implantation kit
US5540711A (en) 1992-06-02 1996-07-30 General Surgical Innovations, Inc. Apparatus and method for developing an anatomic space for laparoscopic procedures with laparoscopic visualization
FR2694882B1 (en) 1992-08-24 1994-10-21 Sofamor Intervertebral disc prosthesis.
US5257632A (en) 1992-09-09 1993-11-02 Symbiosis Corporation Coaxial bone marrow biopsy coring and aspirating needle assembly and method of use thereof
JPH06178787A (en) 1992-12-14 1994-06-28 Shima Yumiko Centrum spacer with joint, intervertebral cavity measuring device and centrum spacer pattern
US5534023A (en) 1992-12-29 1996-07-09 Henley; Julian L. Fluid filled prosthesis excluding gas-filled beads
US5676701A (en) 1993-01-14 1997-10-14 Smith & Nephew, Inc. Low wear artificial spinal disc
US5669926A (en) 1993-01-25 1997-09-23 Aust & Taylor Medical Corporation Surgical instrument
ES2161725T3 (en) 1993-02-09 2001-12-16 Depuy Acromed Inc INTERVERTEBRAL DISC.
US5441538A (en) 1993-04-12 1995-08-15 Bonutti; Peter M. Bone implant and method of securing
US5985307A (en) 1993-04-14 1999-11-16 Emory University Device and method for non-occlusive localized drug delivery
EP0621020A1 (en) 1993-04-21 1994-10-26 SULZER Medizinaltechnik AG Intervertebral prosthesis and method of implanting such a prosthesis
US5383932A (en) 1993-04-27 1995-01-24 Johnson & Johnson Professional, Inc. Absorbable medullary plug
US5403348A (en) 1993-05-14 1995-04-04 Bonutti; Peter M. Suture anchor
FR2707480B1 (en) 1993-06-28 1995-10-20 Bisserie Michel Intervertebral disc prosthesis.
US5645596A (en) 1993-07-07 1997-07-08 Asahi Kogaku Kogyo Kabushiki Kaisha Ceramic vertebrae prosthesis
US5423817A (en) 1993-07-29 1995-06-13 Lin; Chih-I Intervertebral fusing device
US5423816A (en) 1993-07-29 1995-06-13 Lin; Chih I. Intervertebral locking device
DE4328062A1 (en) 1993-08-20 1995-02-23 Heinrich Ulrich Implant to replace vertebral bodies and / or to stabilize and fix the spine
DE4328690B4 (en) 1993-08-26 2006-08-17 SDGI Holdings, Inc., Wilmington Intervertebral implant for vertebral body blocking and implantation instrument for positioning the intervertebral implant
US5372660A (en) 1993-08-26 1994-12-13 Smith & Nephew Richards, Inc. Surface and near surface hardened medical implants
US5458641A (en) 1993-09-08 1995-10-17 Ramirez Jimenez; Juan J. Vertebral body prosthesis
FR2709949B1 (en) 1993-09-14 1995-10-13 Commissariat Energie Atomique Intervertebral disc prosthesis.
BE1007549A3 (en) 1993-09-21 1995-08-01 Beckers Louis Francois Charles Implant.
US5423850A (en) 1993-10-01 1995-06-13 Berger; J. Lee Balloon compressor for internal fixation of bone fractures
US5480400A (en) 1993-10-01 1996-01-02 Berger; J. Lee Method and device for internal fixation of bone fractures
CN1156255C (en) 1993-10-01 2004-07-07 美商-艾克罗米德公司 Spinal implant
US6197065B1 (en) 1993-11-01 2001-03-06 Biomet, Inc. Method and apparatus for segmental bone replacement
FR2712486A1 (en) 1993-11-19 1995-05-24 Breslave Patrice Intervertebral prosthesis
US5522398A (en) 1994-01-07 1996-06-04 Medsol Corp. Bone marrow biopsy needle
US5514180A (en) 1994-01-14 1996-05-07 Heggeness; Michael H. Prosthetic intervertebral devices
US20030032963A1 (en) 2001-10-24 2003-02-13 Kyphon Inc. Devices and methods using an expandable body with internal restraint for compressing cancellous bone
FR2715293B1 (en) 1994-01-26 1996-03-22 Biomat Vertebral interbody fusion cage.
US20030229372A1 (en) 1994-01-26 2003-12-11 Kyphon Inc. Inflatable device for use in surgical protocols relating to treatment of fractured or diseased bone
US6248110B1 (en) 1994-01-26 2001-06-19 Kyphon, Inc. Systems and methods for treating fractured or diseased bone using expandable bodies
US7044954B2 (en) 1994-01-26 2006-05-16 Kyphon Inc. Method for treating a vertebral body
US20060100635A1 (en) 1994-01-26 2006-05-11 Kyphon, Inc. Inflatable device for use in surgical protocol relating to fixation of bone
US6241734B1 (en) 1998-08-14 2001-06-05 Kyphon, Inc. Systems and methods for placing materials into bone
US6716216B1 (en) 1998-08-14 2004-04-06 Kyphon Inc. Systems and methods for treating vertebral bodies
US7166121B2 (en) 1994-01-26 2007-01-23 Kyphon Inc. Systems and methods using expandable bodies to push apart cortical bone surfaces
ATE293395T1 (en) 1994-01-26 2005-05-15 Kyphon Inc IMPROVED INFLATABLE DEVICE FOR USE IN SURGICAL PROTOCOLS RELATING TO BONE FIXATION
EP0741547B1 (en) 1994-01-26 2005-04-20 Kyphon Inc. Improved inflatable device for use in surgical protocol relating to fixation of bone
US5468245A (en) 1994-02-03 1995-11-21 Vargas, Iii; Joseph H. Biomedical cement bonding enhancer
US5431658A (en) 1994-02-14 1995-07-11 Moskovich; Ronald Facilitator for vertebrae grafts and prostheses
FR2716612B1 (en) 1994-02-25 1996-04-26 Vermon Ultrasound ultrasound endoscope.
US5697977A (en) 1994-03-18 1997-12-16 Pisharodi; Madhavan Method and apparatus for spondylolisthesis reduction
US5893890A (en) 1994-03-18 1999-04-13 Perumala Corporation Rotating, locking intervertebral disk stabilizer and applicator
US6093207A (en) 1994-03-18 2000-07-25 Pisharodi; Madhavan Middle expanded, removable intervertebral disk stabilizer disk
FR2718635B1 (en) 1994-04-15 1996-07-05 Axcyl Medical Cervical prosthesis.
EP0678489A1 (en) 1994-04-19 1995-10-25 Fraunhofer-Gesellschaft Zur Förderung Der Angewandten Forschung E.V. Sintered alumina and procces for its production
FR2719763B1 (en) 1994-05-11 1996-09-27 Jean Taylor Vertebral implant.
US5454827A (en) 1994-05-24 1995-10-03 Aust; Gilbert M. Surgical instrument
US5538009A (en) 1994-07-21 1996-07-23 Baxter International, Inc. Biopsy needle assembly
US5980522A (en) 1994-07-22 1999-11-09 Koros; Tibor Expandable spinal implants
DE69522060T2 (en) 1994-09-08 2002-05-29 Stryker Technologies Corp Intervertebral disc core made of hydrogel
EP0786963B1 (en) 1994-10-17 2004-04-07 RayMedica, Inc. Prosthetic spinal disc nucleus
US5824093A (en) 1994-10-17 1998-10-20 Raymedica, Inc. Prosthetic spinal disc nucleus
US5674296A (en) 1994-11-14 1997-10-07 Spinal Dynamics Corporation Human spinal disc prosthesis
EP1512385B1 (en) 1994-12-09 2006-05-03 SDGI Holdings, Inc. Adjustable vertebral body replacement
HU215016B (en) 1995-01-24 1998-08-28 Róbert Mező Fixating device for diarthrosis of limbs
US5766252A (en) 1995-01-24 1998-06-16 Osteonics Corp. Interbody spinal prosthetic implant and method
US5665122A (en) 1995-01-31 1997-09-09 Kambin; Parviz Expandable intervertebral cage and surgical method
FR2730159B1 (en) 1995-02-06 1997-04-25 Teule Jean Germain PROSTHESIS FOR INTERVERTEBRAL DISC
SE509703C2 (en) 1995-02-07 1999-03-01 Sven Olerud Two devices for locking two implant elements to each other
ES2161845T3 (en) 1995-02-17 2001-12-16 Sulzer Orthopadie Ag APPARATUS FOR PLACING AN INTRAMEDULAR SHUTTER IN THE MEDULAR CHANNEL OF A TUBULAR BONE.
CN1134810A (en) 1995-02-17 1996-11-06 索发默达纳集团股份有限公司 Improved interbody spinal fusion implants
US5860973A (en) 1995-02-27 1999-01-19 Michelson; Gary Karlin Translateral spinal implant
US5658335A (en) 1995-03-09 1997-08-19 Cohort Medical Products Group, Inc. Spinal fixator
DE19509116C2 (en) 1995-03-16 2000-01-05 Deutsch Zentr Luft & Raumfahrt Flexible structure
US5575790A (en) 1995-03-28 1996-11-19 Rensselaer Polytechnic Institute Shape memory alloy internal linear actuator for use in orthopedic correction
EP0743045A2 (en) 1995-04-28 1996-11-20 Gazzani, Romolo Igino Devices for osteosynthesis
US20050131268A1 (en) 1995-06-07 2005-06-16 Talmadge Karen D. System and method for delivering a therapeutic agent for bone disease
US20050131267A1 (en) 1995-06-07 2005-06-16 Talmadge Karen D. System and method for delivering a therapeutic agent for bone disease
US20050131269A1 (en) 1995-06-07 2005-06-16 Talmadge Karen D. System and method for delivering a therapeutic agent for bone disease
AU6144496A (en) 1995-06-19 1997-01-15 Sven Olerud An adjustable spacing device and a method of adjusting the distance between two vertebrae with the aid of said spacing device in spinal surgical operations
US5807275A (en) 1995-07-19 1998-09-15 Medical Biopsy, Inc. Biopsy needle
DE19549426C2 (en) 1995-08-11 1997-10-09 Bernhard Zientek Intervertebral implant and instrument therefor
US6095149A (en) 1996-08-13 2000-08-01 Oratec Interventions, Inc. Method for treating intervertebral disc degeneration
DE19541114A1 (en) 1995-10-26 1997-04-30 Artos Med Produkte Intervertebral implant
ES2278091T3 (en) 1995-11-08 2007-08-01 Zimmer Gmbh DEVICE FOR INTRODUCING AN IMPLANT, IN PARTICULAR AN INTERVERTEBRAL PROTESIS.
US5645597A (en) 1995-12-29 1997-07-08 Krapiva; Pavel I. Disc replacement method and apparatus
US5695513A (en) 1996-03-01 1997-12-09 Metagen, Llc Flexible cutting tool and methods for its use
CA2199462C (en) 1996-03-14 2006-01-03 Charles J. Winslow Method and instrumentation for implant insertion
US5683465A (en) 1996-03-18 1997-11-04 Shinn; Gary Lee Artificial intervertebral disk prosthesis
US5653763A (en) 1996-03-29 1997-08-05 Fastenetix, L.L.C. Intervertebral space shape conforming cage device
FR2748387B1 (en) 1996-05-13 1998-10-30 Stryker France Sa BONE FIXATION DEVICE, IN PARTICULAR TO THE SACRUM, IN OSTEOSYNTHESIS OF THE SPINE
DE19622827B4 (en) 1996-06-07 2009-04-23 Ulrich, Heinrich Implant for insertion between vertebrae as a placeholder
US7069087B2 (en) 2000-02-25 2006-06-27 Oratec Interventions, Inc. Apparatus and method for accessing and performing a function within an intervertebral disc
US5716416A (en) 1996-09-10 1998-02-10 Lin; Chih-I Artificial intervertebral disk and method for implanting the same
FR2753368B1 (en) 1996-09-13 1999-01-08 Chauvin Jean Luc EXPANSIONAL OSTEOSYNTHESIS CAGE
US5782832A (en) 1996-10-01 1998-07-21 Surgical Dynamics, Inc. Spinal fusion implant and method of insertion thereof
WO1998017207A1 (en) 1996-10-21 1998-04-30 Synthes Ag Chur Surgical prosthetic device
US5756127A (en) 1996-10-29 1998-05-26 Wright Medical Technology, Inc. Implantable bioresorbable string of calcium sulfate beads
US6190414B1 (en) 1996-10-31 2001-02-20 Surgical Dynamics Inc. Apparatus for fusion of adjacent bone structures
US6602293B1 (en) 1996-11-01 2003-08-05 The Johns Hopkins University Polymeric composite orthopedic implant
US5895428A (en) 1996-11-01 1999-04-20 Berry; Don Load bearing spinal joint implant
US5925074A (en) 1996-12-03 1999-07-20 Atrium Medical Corporation Vascular endoprosthesis and method
US5961554A (en) 1996-12-31 1999-10-05 Janson; Frank S Intervertebral spacer
US7959652B2 (en) 2005-04-18 2011-06-14 Kyphon Sarl Interspinous process implant having deployable wings and method of implantation
US6451019B1 (en) 1998-10-20 2002-09-17 St. Francis Medical Technologies, Inc. Supplemental spine fixation device and method
US7201751B2 (en) 1997-01-02 2007-04-10 St. Francis Medical Technologies, Inc. Supplemental spine fixation device
US6796983B1 (en) 1997-01-02 2004-09-28 St. Francis Medical Technologies, Inc. Spine distraction implant and method
US6068630A (en) 1997-01-02 2000-05-30 St. Francis Medical Technologies, Inc. Spine distraction implant
US5860977A (en) 1997-01-02 1999-01-19 Saint Francis Medical Technologies, Llc Spine distraction implant and method
US6174337B1 (en) 1997-01-06 2001-01-16 Pinnacle Research Institute, Inc. Method of construction of electrochemical cell device using capillary tubing and optional permselective polymers
CA2279911C (en) 1997-02-06 2006-12-05 Charles Dean Ray Expandable non-threaded spinal fusion device
US6039761A (en) 1997-02-12 2000-03-21 Li Medical Technologies, Inc. Intervertebral spacer and tool and method for emplacement thereof
JP2001527437A (en) 1997-03-07 2001-12-25 ベイヤー、モルデキイ System for percutaneous bone and spine stabilization, fixation and repair
IL128261A0 (en) 1999-01-27 1999-11-30 Disc O Tech Medical Tech Ltd Expandable element
US20070282443A1 (en) 1997-03-07 2007-12-06 Disc-O-Tech Medical Technologies Ltd. Expandable element
DE19710392C1 (en) 1997-03-13 1999-07-01 Haehnel Michael Slipped disc implant comprises an extensible, hinged or wound body
US6048360A (en) 1997-03-18 2000-04-11 Endotex Interventional Systems, Inc. Methods of making and using coiled sheet graft for single and bifurcated lumens
US6033412A (en) 1997-04-03 2000-03-07 Losken; H. Wolfgang Automated implantable bone distractor for incremental bone adjustment
US6641614B1 (en) 1997-05-01 2003-11-04 Spinal Concepts, Inc. Multi-variable-height fusion device
US6045579A (en) 1997-05-01 2000-04-04 Spinal Concepts, Inc. Adjustable height fusion device
US6119044A (en) 1997-06-02 2000-09-12 Advanced Bionics Corporation Cochlear electrode array with positioning stylet
US5972015A (en) 1997-08-15 1999-10-26 Kyphon Inc. Expandable, asymetric structures for deployment in interior body regions
US5851212A (en) 1997-06-11 1998-12-22 Endius Incorporated Surgical instrument
US6113640A (en) 1997-06-11 2000-09-05 Bionx Implants Oy Reconstructive bioabsorbable joint prosthesis
US5893889A (en) 1997-06-20 1999-04-13 Harrington; Michael Artificial disc
WO1999002214A1 (en) * 1997-07-09 1999-01-21 Tegementa, L.L.C. Interbody device and method for treatment of osteoporotic vertebral collapse
US6709418B1 (en) 1997-07-11 2004-03-23 A-Med Systems, Inc. Apparatus and methods for entering cavities of the body
US6146421A (en) 1997-08-04 2000-11-14 Gordon, Maya, Roberts And Thomas, Number 1, Llc Multiple axis intervertebral prosthesis
US6048346A (en) 1997-08-13 2000-04-11 Kyphon Inc. Systems and methods for injecting flowable materials into bones
US5865848A (en) 1997-09-12 1999-02-02 Artifex, Ltd. Dynamic intervertebral spacer and method of use
US5824094A (en) 1997-10-17 1998-10-20 Acromed Corporation Spinal disc
EP1027004B1 (en) 1997-10-27 2007-12-12 St. Francis Medical Technologies, Inc. Spine distraction implant
US6652592B1 (en) 1997-10-27 2003-11-25 Regeneration Technologies, Inc. Segmentally demineralized bone implant
US6139579A (en) 1997-10-31 2000-10-31 Depuy Motech Acromed, Inc. Spinal disc
US5888226A (en) 1997-11-12 1999-03-30 Rogozinski; Chaim Intervertebral prosthetic disc
DE19750382A1 (en) 1997-11-13 1999-05-20 Augustin Prof Dr Med Betz Operative correction equipment for displaced vertebrae used in minimally invasive surgery
US6146420A (en) 1997-12-10 2000-11-14 Sdgi Holdings, Inc. Osteogenic fusion device
US6648916B1 (en) 1997-12-10 2003-11-18 Sdgi Holdings, Inc. Osteogenic fusion device
US6162252A (en) 1997-12-12 2000-12-19 Depuy Acromed, Inc. Artificial spinal disc
FR2772594B1 (en) 1997-12-19 2000-05-05 Henry Graf REAR PARTIAL DISCAL PROSTHESIS
US6468279B1 (en) 1998-01-27 2002-10-22 Kyphon Inc. Slip-fit handle for hand-held instruments that access interior body regions
US7087082B2 (en) 1998-08-03 2006-08-08 Synthes (Usa) Bone implants with central chambers
DE19807236C2 (en) 1998-02-20 2000-06-21 Biedermann Motech Gmbh Intervertebral implant
US5989291A (en) 1998-02-26 1999-11-23 Third Millennium Engineering, Llc Intervertebral spacer device
US6045552A (en) 1998-03-18 2000-04-04 St. Francis Medical Technologies, Inc. Spine fixation plate system
US6224631B1 (en) 1998-03-20 2001-05-01 Sulzer Spine-Tech Inc. Intervertebral implant with reduced contact area and method
US6835208B2 (en) 1998-03-30 2004-12-28 J. Alexander Marchosky Prosthetic system
WO1999049818A1 (en) 1998-03-30 1999-10-07 Marchosky J Alexander Prosthetic system
US6440138B1 (en) 1998-04-06 2002-08-27 Kyphon Inc. Structures and methods for creating cavities in interior body regions
US6428541B1 (en) 1998-04-09 2002-08-06 Sdgi Holdings, Inc. Method and instrumentation for vertebral interbody fusion
ATE274844T1 (en) 1998-04-09 2004-09-15 Sdgi Holdings Inc VERTEBRATE BODY DISTRACTOR
US6197033B1 (en) 1998-04-09 2001-03-06 Sdgi Holdings, Inc. Guide sleeve for offset vertebrae
US6019792A (en) 1998-04-23 2000-02-01 Cauthen Research Group, Inc. Articulating spinal implant
US6179874B1 (en) 1998-04-23 2001-01-30 Cauthen Research Group, Inc. Articulating spinal implant
US6241769B1 (en) 1998-05-06 2001-06-05 Cortek, Inc. Implant for spinal fusion
WO1999060956A1 (en) 1998-05-27 1999-12-02 Nuvasive, Inc. Interlocking spinal inserts
US6290724B1 (en) 1998-05-27 2001-09-18 Nuvasive, Inc. Methods for separating and stabilizing adjacent vertebrae
US6368325B1 (en) * 1998-05-27 2002-04-09 Nuvasive, Inc. Bone blocks and methods for inserting bone blocks into intervertebral spaces
US6719773B1 (en) 1998-06-01 2004-04-13 Kyphon Inc. Expandable structures for deployment in interior body regions
DE69942858D1 (en) 1998-06-01 2010-11-25 Kyphon S A R L DEFINABLE, PREFORMED STRUCTURES FOR ESTABLISHMENT IN REGIONS INSIDE THE BODY
AU4422899A (en) 1998-06-09 2000-02-14 Nuvasive, Inc. Spinal surgery guidance platform
US6224603B1 (en) 1998-06-09 2001-05-01 Nuvasive, Inc. Transiliac approach to entering a patient's intervertebral space
US6126689A (en) 1998-06-15 2000-10-03 Expanding Concepts, L.L.C. Collapsible and expandable interbody fusion device
US6136031A (en) 1998-06-17 2000-10-24 Surgical Dynamics, Inc. Artificial intervertebral disc
US6682561B2 (en) 1998-06-18 2004-01-27 Pioneer Laboratories, Inc. Spinal fixation system
GB2338652A (en) 1998-06-23 1999-12-29 Biomet Merck Ltd Vertebral body replacement
DE29813139U1 (en) 1998-07-23 1998-12-03 Howmedica Gmbh Vertebral body reconstruction system
US6126660A (en) 1998-07-29 2000-10-03 Sofamor Danek Holdings, Inc. Spinal compression and distraction devices and surgical methods
US6063121A (en) 1998-07-29 2000-05-16 Xavier; Ravi Vertebral body prosthesis
DE29814174U1 (en) 1998-08-07 1999-12-16 Howmedica Gmbh Instruments for inserting an implant into the human spine
US20050228397A1 (en) 1998-08-14 2005-10-13 Malandain Hugues F Cavity filling device
US6099531A (en) 1998-08-20 2000-08-08 Bonutti; Peter M. Changing relationship between bones
US6146387A (en) 1998-08-26 2000-11-14 Linvatec Corporation Cannulated tissue anchor system
FR2782632B1 (en) 1998-08-28 2000-12-29 Materiel Orthopedique En Abreg EXPANSIBLE INTERSOMATIC FUSION CAGE
EP1109517B1 (en) 1998-09-04 2006-07-12 SDGI Holdings, Inc. Cylindrical hemi-lunar parallel array threaded disc prosthesis
US6117174A (en) 1998-09-16 2000-09-12 Nolan; Wesley A. Spinal implant device
US6090143A (en) 1998-09-21 2000-07-18 Meriwether; Michael W. Box cage for intervertebral body fusion
US6030401A (en) 1998-10-07 2000-02-29 Nuvasive, Inc. Vertebral enplate decorticator and osteophyte resector
ATE385411T1 (en) 1998-10-20 2008-02-15 Synthes Gmbh TENSION REGULATING FUSION CAGE FOR SPINAL FUSION SURGERY
US6113637A (en) 1998-10-22 2000-09-05 Sofamor Danek Holdings, Inc. Artificial intervertebral joint permitting translational and rotational motion
US6159211A (en) 1998-10-22 2000-12-12 Depuy Acromed, Inc. Stackable cage system for corpectomy/vertebrectomy
US6554833B2 (en) 1998-10-26 2003-04-29 Expanding Orthopedics, Inc. Expandable orthopedic device
US6261289B1 (en) 1998-10-26 2001-07-17 Mark Levy Expandable orthopedic device
US6039763A (en) 1998-10-27 2000-03-21 Disc Replacement Technologies, Inc. Articulating spinal disc prosthesis
US6193757B1 (en) 1998-10-29 2001-02-27 Sdgi Holdings, Inc. Expandable intervertebral spacers
US6179794B1 (en) 1998-11-19 2001-01-30 Jon Burras Adjustable vibrating head massaging device
KR20010040761A (en) 1998-12-09 2001-05-15 쿡 인코포레이티드 Hollow, Curved, Superelastic Medical Needle
FR2787014B1 (en) 1998-12-11 2001-03-02 Dimso Sa INTERVERTEBRAL DISC PROSTHESIS WITH REDUCED FRICTION
FR2787017B1 (en) 1998-12-11 2001-04-27 Dimso Sa INTERVERTEBRAL DISC PROSTHESIS WITH IMPROVED MECHANICAL BEHAVIOR
FR2787016B1 (en) 1998-12-11 2001-03-02 Dimso Sa INTERVERTEBRAL DISK PROSTHESIS
FR2787015B1 (en) 1998-12-11 2001-04-27 Dimso Sa INTERVERTEBRAL DISC PROSTHESIS WITH COMPRESSIBLE BODY
FR2787019B1 (en) 1998-12-11 2001-03-02 Dimso Sa INTERVERTEBRAL DISC PROSTHESIS WITH IMPROVED MECHANICAL BEHAVIOR
BR9805340B1 (en) 1998-12-14 2009-01-13 variable expansion insert for spinal stabilization.
US6159244A (en) 1999-07-30 2000-12-12 Suddaby; Loubert Expandable variable angle intervertebral fusion implant
US6183517B1 (en) 1998-12-16 2001-02-06 Loubert Suddaby Expandable intervertebral fusion implant and applicator
US6280447B1 (en) 1998-12-23 2001-08-28 Nuvasive, Inc. Bony tissue resector
US6102950A (en) 1999-01-19 2000-08-15 Vaccaro; Alex Intervertebral body fusion device
US6547823B2 (en) 1999-01-22 2003-04-15 Osteotech, Inc. Intervertebral implant
US7621950B1 (en) 1999-01-27 2009-11-24 Kyphon Sarl Expandable intervertebral spacer
DE19903762C1 (en) 1999-01-30 2000-11-16 Aesculap Ag & Co Kg Surgical instrument for inserting intervertebral implants
US6648895B2 (en) 2000-02-04 2003-11-18 Sdgi Holdings, Inc. Methods and instrumentation for vertebral interbody fusion
US6743234B2 (en) 1999-02-04 2004-06-01 Sdgi Holdings, Inc. Methods and instrumentation for vertebral interbody fusion
US8133421B2 (en) 1999-02-23 2012-03-13 Warsaw Orthopedic, Inc. Methods of making shaped load-bearing osteoimplant
US6206883B1 (en) 1999-03-05 2001-03-27 Stryker Technologies Corporation Bioabsorbable materials and medical devices made therefrom
CA2591678C (en) 1999-03-07 2008-05-20 Active Implants Corporation Method and apparatus for computerized surgery
US6368350B1 (en) 1999-03-11 2002-04-09 Sulzer Spine-Tech Inc. Intervertebral disc prosthesis and method
US6267763B1 (en) 1999-03-31 2001-07-31 Surgical Dynamics, Inc. Method and apparatus for spinal implant insertion
US6110210A (en) 1999-04-08 2000-08-29 Raymedica, Inc. Prosthetic spinal disc nucleus having selectively coupled bodies
AU4246000A (en) 1999-04-16 2000-11-02 Nuvasive, Inc. Articulation systems for positioning minimally invasive surgical tools
US6478805B1 (en) 1999-04-16 2002-11-12 Nuvasive, Inc. System for removing cut tissue from the inner bore of a surgical instrument
US6491626B1 (en) 1999-04-16 2002-12-10 Nuvasive Articulation systems for positioning minimally invasive surgical tools
AU4810800A (en) 1999-04-26 2000-11-10 Li Medical Technologies, Inc. Prosthetic apparatus and method
US6238491B1 (en) 1999-05-05 2001-05-29 Davitech, Inc. Niobium-titanium-zirconium-molybdenum (nbtizrmo) alloys for dental and other medical device applications
AU778448B2 (en) 1999-05-07 2004-12-02 University Of Virginia Patent Foundation Method and system for fusing a spinal region
US6607530B1 (en) 1999-05-10 2003-08-19 Highgate Orthopedics, Inc. Systems and methods for spinal fixation
US6520991B2 (en) 1999-05-11 2003-02-18 Donald R. Huene Expandable implant for inter-vertebral stabilization, and a method of stabilizing vertebrae
US6964686B2 (en) 1999-05-17 2005-11-15 Vanderbilt University Intervertebral disc replacement prosthesis
DE59904848D1 (en) 1999-05-21 2003-05-08 Link Waldemar Gmbh Co Intervertebral endoprosthesis with a toothed connecting plate
US6245107B1 (en) 1999-05-28 2001-06-12 Bret A. Ferree Methods and apparatus for treating disc herniation
US6969404B2 (en) 1999-10-08 2005-11-29 Ferree Bret A Annulus fibrosis augmentation methods and apparatus
US6491724B1 (en) 1999-08-13 2002-12-10 Bret Ferree Spinal fusion cage with lordosis correction
FR2794362B1 (en) 1999-06-02 2001-09-21 Henry Graf INTERVERTEBRAL IMPLANT AND POSITIONING ASSEMBLY OF SUCH AN IMPLANT
US6520996B1 (en) 1999-06-04 2003-02-18 Depuy Acromed, Incorporated Orthopedic implant
CA2376097A1 (en) 1999-06-04 2000-12-14 Sdgi Holdings, Inc. Artificial disc implant
US6277149B1 (en) * 1999-06-08 2001-08-21 Osteotech, Inc. Ramp-shaped intervertebral implant
US6419705B1 (en) 1999-06-23 2002-07-16 Sulzer Spine-Tech Inc. Expandable fusion device and method
US7637905B2 (en) 2003-01-15 2009-12-29 Usgi Medical, Inc. Endoluminal tool deployment system
WO2001001895A1 (en) 1999-07-02 2001-01-11 Petrus Besselink Reinforced expandable cage
ES2303381T3 (en) 1999-07-02 2008-08-01 Spine Solutions Inc. INTERVERTEBRAL IMPLANT.
WO2002009626A1 (en) 1999-07-26 2002-02-07 Advanced Prosthetic Technologies, Inc. Improved spinal surgical prosthesis
US7824445B2 (en) 1999-07-26 2010-11-02 Ladislau Biro Corpectomy vertebral body replacement implant system
US6454806B1 (en) 1999-07-26 2002-09-24 Advanced Prosthetic Technologies, Inc. Spinal surgical prosthesis
NL1012719C1 (en) 1999-07-28 2001-01-30 Veldhuizen Dr Ag Spine prosthesis.
US7220281B2 (en) 1999-08-18 2007-05-22 Intrinsic Therapeutics, Inc. Implant for reinforcing and annulus fibrosis
EP1328221B1 (en) 1999-08-18 2009-03-25 Intrinsic Therapeutics, Inc. Devices for nucleus pulposus augmentation and retention
US7553329B2 (en) 1999-08-18 2009-06-30 Intrinsic Therapeutics, Inc. Stabilized intervertebral disc barrier
US6425919B1 (en) 1999-08-18 2002-07-30 Intrinsic Orthopedics, Inc. Devices and methods of vertebral disc augmentation
US7717961B2 (en) 1999-08-18 2010-05-18 Intrinsic Therapeutics, Inc. Apparatus delivery in an intervertebral disc
US6821276B2 (en) 1999-08-18 2004-11-23 Intrinsic Therapeutics, Inc. Intervertebral diagnostic and manipulation device
US7507243B2 (en) 1999-08-18 2009-03-24 Gregory Lambrecht Devices and method for augmenting a vertebral disc
US6508839B1 (en) 1999-08-18 2003-01-21 Intrinsic Orthopedics, Inc. Devices and methods of vertebral disc augmentation
US6866682B1 (en) 1999-09-02 2005-03-15 Stryker Spine Distractable corpectomy device
EP1212013B1 (en) 1999-09-08 2006-02-08 Depuy International Limited Combination of material for joint prosthesis
EP1792588B1 (en) 1999-09-14 2013-12-18 Spine Solutions Inc. Insert instrument for an implant between vertebrae
US6964674B1 (en) 1999-09-20 2005-11-15 Nuvasive, Inc. Annulotomy closure device
US20040186573A1 (en) 1999-10-08 2004-09-23 Ferree Bret A. Annulus fibrosis augmentation methods and apparatus
US20030040796A1 (en) 1999-10-08 2003-02-27 Ferree Bret A. Devices used to treat disc herniation and attachment mechanisms therefore
US6878167B2 (en) 2002-04-24 2005-04-12 Bret A. Ferree Methods and apparatus for placing intradiscal devices
US6436101B1 (en) 1999-10-13 2002-08-20 James S. Hamada Rasp for use in spine surgery
USD439980S1 (en) 1999-10-19 2001-04-03 Kyphon, Inc. Hand-held surgical instrument
US6575919B1 (en) 1999-10-19 2003-06-10 Kyphon Inc. Hand-held instruments that access interior body regions
US7081122B1 (en) 1999-10-19 2006-07-25 Kyphon Inc. Hand-held instruments that access interior body regions
USD449691S1 (en) 1999-10-19 2001-10-23 Kyphon Inc. Hand-held surgical instrument
US6500180B1 (en) 1999-10-20 2002-12-31 Sdgi Holdings, Inc. Methods and instrumentation for distraction of a disc space
US20030153976A1 (en) 1999-10-20 2003-08-14 Cauthen Joseph C. Spinal disc annulus reconstruction method and spinal disc annulus stent
US7052516B2 (en) 1999-10-20 2006-05-30 Anulex Technologies, Inc. Spinal disc annulus reconstruction method and deformable spinal disc annulus stent
US6780151B2 (en) 1999-10-26 2004-08-24 Acmi Corporation Flexible ureteropyeloscope
US6749560B1 (en) 1999-10-26 2004-06-15 Circon Corporation Endoscope shaft with slotted tube
US6491695B1 (en) 1999-11-05 2002-12-10 Carl Roggenbuck Apparatus and method for aligning vertebrae
US6533797B1 (en) 1999-11-24 2003-03-18 Nuvasive Control grip assembly
US6592624B1 (en) 1999-11-24 2003-07-15 Depuy Acromed, Inc. Prosthetic implant element
JP4672947B2 (en) 1999-12-06 2011-04-20 ウォーソー・オーソペディック・インコーポレーテッド Intervertebral disc treatment apparatus and method
US6485518B1 (en) 1999-12-10 2002-11-26 Nuvasive Facet screw and bone allograft intervertebral support and fusion system
CA2328818A1 (en) 1999-12-16 2001-06-16 Isotis B.V. Porous ceramic body
SK8232002A3 (en) 1999-12-17 2003-05-02 Cartificial As Medico Chemical A prosthetic device
US20050187564A1 (en) 1999-12-23 2005-08-25 Swaminathan Jayaraman Occlusive coil manufacturing and delivery
US6364828B1 (en) 2000-01-06 2002-04-02 Hubert K. Yeung Elongated flexible inspection neck
EP1645248B8 (en) 2000-02-04 2010-06-16 Warsaw Orthopedic, Inc. Expandable interbody spinal fusion implant having pivotally attached blocker
US6709458B2 (en) 2000-02-04 2004-03-23 Gary Karlin Michelson Expandable push-in arcuate interbody spinal fusion implant with tapered configuration during insertion
US6716247B2 (en) 2000-02-04 2004-04-06 Gary K. Michelson Expandable push-in interbody spinal fusion implant
US6814756B1 (en) 2000-02-04 2004-11-09 Gary K. Michelson Expandable threaded arcuate interbody spinal fusion implant with lordotic configuration during insertion
US6500205B1 (en) 2000-04-19 2002-12-31 Gary K. Michelson Expandable threaded arcuate interbody spinal fusion implant with cylindrical configuration during insertion
US6899716B2 (en) 2000-02-16 2005-05-31 Trans1, Inc. Method and apparatus for spinal augmentation
US7014633B2 (en) 2000-02-16 2006-03-21 Trans1, Inc. Methods of performing procedures in the spine
EP1578315B2 (en) 2000-02-16 2011-12-07 TRANS1, Inc. Apparatus for spinal distraction and fusion
US6558390B2 (en) 2000-02-16 2003-05-06 Axiamed, Inc. Methods and apparatus for performing therapeutic procedures in the spine
US6575979B1 (en) 2000-02-16 2003-06-10 Axiamed, Inc. Method and apparatus for providing posterior or anterior trans-sacral access to spinal vertebrae
FR2805733B1 (en) 2000-03-03 2002-06-07 Scient X DISC PROSTHESIS FOR CERVICAL VERTEBRUS
US6332895B1 (en) 2000-03-08 2001-12-25 Loubert Suddaby Expandable intervertebral fusion implant having improved stability
AU4554101A (en) 2000-03-10 2001-09-24 Sdgi Holdings Inc Synthetic reinforced interbody fusion implants
FR2805985B1 (en) 2000-03-10 2003-02-07 Eurosurgical INTERVERTEBRAL DISK PROSTHESIS
AR027685A1 (en) 2000-03-22 2003-04-09 Synthes Ag METHOD AND METHOD FOR CARRYING OUT
ES2262637T3 (en) 2000-03-31 2006-12-01 Konigsee Implantate Und Instrumente Zur Ostheosynthese Gmbh IMPLANT FOR ADJUSTABLE VERTEBRAL BODY IN HEIGHT AND INSTRUMENT KIT TO MANIPULATE IT.
US6402750B1 (en) 2000-04-04 2002-06-11 Spinlabs, Llc Devices and methods for the treatment of spinal disorders
US6579291B1 (en) 2000-10-10 2003-06-17 Spinalabs, Llc Devices and methods for the treatment of spinal disorders
US6805695B2 (en) 2000-04-04 2004-10-19 Spinalabs, Llc Devices and methods for annular repair of intervertebral discs
US6689125B1 (en) 2000-04-04 2004-02-10 Spinalabs, Llc Devices and methods for the treatment of spinal disorders
EP1272131B1 (en) 2000-04-05 2006-03-01 Kyphon Inc. Devices for treating fractured and/or diseased bone
KR100882365B1 (en) 2000-04-07 2009-02-05 키폰 에스에이알엘 Insertion devices and method of use
US7815649B2 (en) 2000-04-07 2010-10-19 Kyphon SÀRL Insertion devices and method of use
US7867186B2 (en) 2002-04-08 2011-01-11 Glaukos Corporation Devices and methods for treatment of ocular disorders
US6821298B1 (en) 2000-04-18 2004-11-23 Roger P. Jackson Anterior expandable spinal fusion cage system
US6350283B1 (en) 2000-04-19 2002-02-26 Gary K. Michelson Bone hemi-lumbar interbody spinal implant having an asymmetrical leading end and method of installation thereof
US7462195B1 (en) 2000-04-19 2008-12-09 Warsaw Orthopedic, Inc. Artificial lumbar interbody spinal implant having an asymmetrical leading end
US20020010070A1 (en) 2000-04-25 2002-01-24 Bernard Cales Zirconia-toughened alumina biocomponent having high resistance to low temperature degradation and method for preparing same
US6482234B1 (en) 2000-04-26 2002-11-19 Pearl Technology Holdings, Llc Prosthetic spinal disc
US6478800B1 (en) 2000-05-08 2002-11-12 Depuy Acromed, Inc. Medical installation tool
DE50106944D1 (en) 2000-05-26 2005-09-08 Zimmer Gmbh Winterthur Intervertebral disc replacement for the nucleus of an intervertebral disc
US6579318B2 (en) 2000-06-12 2003-06-17 Ortho Development Corporation Intervertebral spacer
US6875212B2 (en) 2000-06-23 2005-04-05 Vertelink Corporation Curable media for implantable medical device
JP2004500963A (en) 2000-06-27 2004-01-15 カイフォン インコーポレイテッド System and method for injecting flowable material into bone
US7025771B2 (en) 2000-06-30 2006-04-11 Spineology, Inc. Tool to direct bone replacement material
DE10032220A1 (en) 2000-07-03 2002-01-24 Sanatis Gmbh Magnesium ammonium phosphate cements, their manufacture and use
US6419696B1 (en) 2000-07-06 2002-07-16 Paul A. Spence Annuloplasty devices and related heart valve repair methods
US7018416B2 (en) 2000-07-06 2006-03-28 Zimmer Spine, Inc. Bone implants and methods
US6808537B2 (en) 2000-07-07 2004-10-26 Gary Karlin Michelson Expandable implant with interlocking walls
WO2002017801A2 (en) 2000-07-14 2002-03-07 Kyphon Inc. Systems and methods for treating vertebral bodies
US6852126B2 (en) 2000-07-17 2005-02-08 Nuvasive, Inc. Stackable interlocking intervertebral support system
DE60141653D1 (en) 2000-07-21 2010-05-06 Spineology Group Llc A STRONG, POROUS NET BAG DEVICE AND ITS USE IN BONE SURGERY
US6423071B1 (en) 2000-07-25 2002-07-23 Kevin Jon Lawson Surgical tool and method for passing pilot-line sutures through spinal vertebrae
FR2812188B1 (en) 2000-07-31 2003-06-13 Spinevision Sa RACHIS IMMOBILIZATION CAGE AND OSTEOSYNTHESIS, METHOD FOR MANUFACTURING THE CAGE AND DRILLING EQUIPMENT FOR THE LAYOUT OF THE CAGE
US7056321B2 (en) 2000-08-01 2006-06-06 Endius, Incorporated Method of securing vertebrae
JP4617408B2 (en) 2000-08-08 2011-01-26 ワルシャワ オーソピディック、インク. Implantable artificial joint
US20020035400A1 (en) 2000-08-08 2002-03-21 Vincent Bryan Implantable joint prosthesis
AU2001284857B2 (en) 2000-08-11 2005-09-29 Warsaw Orthopedic, Inc. Surgical instrumentation and method for treatment of the spine
US7114501B2 (en) 2000-08-14 2006-10-03 Spine Wave, Inc. Transverse cavity device and method
CN1192750C (en) * 2000-08-28 2005-03-16 迪斯科动力学公司 Prosthesis of vertebral disc
US20050154463A1 (en) 2000-08-30 2005-07-14 Trieu Hal H. Spinal nucleus replacement implants and methods
US20020026244A1 (en) 2000-08-30 2002-02-28 Trieu Hai H. Intervertebral disc nucleus implants and methods
US6620196B1 (en) 2000-08-30 2003-09-16 Sdgi Holdings, Inc. Intervertebral disc nucleus implants and methods
ATE390899T1 (en) 2000-08-30 2008-04-15 Warsaw Orthopedic Inc DISC IMPLANTS
US7503936B2 (en) 2000-08-30 2009-03-17 Warsaw Orthopedic, Inc. Methods for forming and retaining intervertebral disc implants
US7204851B2 (en) 2000-08-30 2007-04-17 Sdgi Holdings, Inc. Method and apparatus for delivering an intervertebral disc implant
US7166107B2 (en) 2000-09-11 2007-01-23 D. Greg Anderson Percutaneous technique and implant for expanding the spinal canal
WO2002026170A2 (en) 2000-09-26 2002-04-04 Neurortho Implants Design, Llc Inter-vertebral disc prosthesis for lumbar rachis through posterior surgery thereof
US6468309B1 (en) 2000-10-05 2002-10-22 Cleveland Clinic Foundation Method and apparatus for stabilizing adjacent bones
WO2002030338A1 (en) 2000-10-10 2002-04-18 Vertx, Inc. Method and appartus for treating a vertebral body
US20020045942A1 (en) 2000-10-16 2002-04-18 Ham Michael J. Procedure for repairing damaged discs
US6723128B2 (en) 2000-10-17 2004-04-20 Chang Jong Uk Prosthetic device for correcting deformity of spine
KR20030068142A (en) 2000-10-25 2003-08-19 카이폰 인코포레이티드 Systems and methods for mixing and transferring flowable materials
USD483495S1 (en) 2000-10-25 2003-12-09 Kyphon Inc. Hand-held mixer for flowable materials
DE60140558D1 (en) 2000-10-25 2009-12-31 Kyphon S A R L SYSTEMS FOR THE REPOSITION OF BROKEN BONE BY MEANS OF A CANNULA FOR THE REPONATION OF BONE FRACTURES
US6582467B1 (en) 2000-10-31 2003-06-24 Vertelink Corporation Expandable fusion cage
US6666891B2 (en) 2000-11-13 2003-12-23 Frank H. Boehm, Jr. Device and method for lumbar interbody fusion
US6419641B1 (en) 2000-11-28 2002-07-16 Promex, Llc Flexible tip medical instrument
US6454807B1 (en) 2000-11-30 2002-09-24 Roger P. Jackson Articulated expandable spinal fusion cage system
WO2002043628A1 (en) 2000-12-01 2002-06-06 Sabitzer Ronald J Method and device for expanding a body cavity
US6443989B1 (en) 2000-12-04 2002-09-03 Roger P. Jackson Posterior expandable fusion cage
US6773460B2 (en) 2000-12-05 2004-08-10 Roger P. Jackson Anterior variable expandable fusion cage
FR2817462B1 (en) 2000-12-05 2003-08-08 Stryker Spine Sa IN SITU INTERSOMATIC SPINAL IMPLANT WITH HARD PASSAGE POINTS
HUP0302127A2 (en) 2000-12-15 2005-12-28 Spineology, Inc. Annulus-reinforcing band
DE10062876C1 (en) 2000-12-16 2002-04-18 Ks Gleitlager Gmbh Connecting rod bearing shell for connecting rod of titanium or titanium alloy has supporting layer of steel material, and on back of support layer has coating of tin-bronze material with thickness of 10-50 micrometers
US6511471B2 (en) 2000-12-22 2003-01-28 Biocardia, Inc. Drug delivery catheters that attach to tissue and methods for their use
US7153304B2 (en) 2000-12-29 2006-12-26 Zimmer Trabecular Metal Technology, Inc. Instrument system for preparing a disc space between adjacent vertebral bodies to receive a repair device
US6663637B2 (en) 2001-01-02 2003-12-16 Robert A Dixon Vertebral distraction stabilizer
US6468311B2 (en) 2001-01-22 2002-10-22 Sdgi Holdings, Inc. Modular interbody fusion implant
US20030054141A1 (en) 2001-01-25 2003-03-20 Worley James Brice Coated articles having enhanced reversible thermal properties and exhibiting improved flexibility, softness, air permeability, or water vapor transport properties
JP4133331B2 (en) 2001-02-04 2008-08-13 ウォーソー・オーソペディック・インコーポレーテッド Apparatus and method for inserting and deploying an expandable interbody spinal fusion implant
US20020107519A1 (en) 2001-02-05 2002-08-08 Dixon Robert A. Dual spreader flange-tube vertebral stabilizer
US6863689B2 (en) 2001-07-16 2005-03-08 Spinecore, Inc. Intervertebral spacer having a flexible wire mesh vertebral body contact element
US6740117B2 (en) 2001-02-15 2004-05-25 Spinecore, Inc. Intervertebral spacer device having a radially thinning slotted belleville spring
US20030069642A1 (en) 2001-10-04 2003-04-10 Ralph James D. Artificial intervertebral disc having a flexible wire mesh vertebral body contact element
US6764515B2 (en) 2001-02-15 2004-07-20 Spinecore, Inc. Intervertebral spacer device utilizing a spirally slotted belleville washer and a rotational mounting
US7169182B2 (en) 2001-07-16 2007-01-30 Spinecore, Inc. Implanting an artificial intervertebral disc
US20030135204A1 (en) 2001-02-15 2003-07-17 Endo Via Medical, Inc. Robotically controlled medical instrument with a flexible section
WO2002098332A1 (en) 2001-02-16 2002-12-12 Sulzer Spine-Tech Inc. Bone implants and methods
US6929647B2 (en) 2001-02-21 2005-08-16 Howmedica Osteonics Corp. Instrumentation and method for implant insertion
US6595998B2 (en) 2001-03-08 2003-07-22 Spinewave, Inc. Tissue distraction device
US6849093B2 (en) 2001-03-09 2005-02-01 Gary K. Michelson Expansion constraining member adapted for use with an expandable interbody spinal fusion implant and method for use thereof
US6632553B2 (en) 2001-03-27 2003-10-14 Mti Microfuel Cells, Inc. Methods and apparatuses for managing effluent products in a fuel cell system
US7128760B2 (en) 2001-03-27 2006-10-31 Warsaw Orthopedic, Inc. Radially expanding interbody spinal fusion implants, instrumentation, and methods of insertion
DE10116412C1 (en) 2001-04-02 2003-01-16 Ulrich Gmbh & Co Kg Implant to be inserted between the vertebral body of the spine
US20050019365A1 (en) 2001-04-02 2005-01-27 Frauchiger Vinzenz M. Bioactive surface layer, particularly for medical implants and prostheses
CA2443001A1 (en) 2001-04-04 2002-10-17 Lawrence G. Rapp Interbody spinal fusion device
US6582433B2 (en) 2001-04-09 2003-06-24 St. Francis Medical Technologies, Inc. Spine fixation device and method
WO2002083004A1 (en) 2001-04-16 2002-10-24 Kyphon Inc. Insertion devices and method of use
DE10119096A1 (en) 2001-04-19 2002-10-24 Keramed Medizintechnik Gmbh New biologically functionalized coatings, useful for e.g. accelerating osteo-integration of implants, e.g. dental or joint implants, comprise resorbable calcium-phosphorus phase containing adhesion and/or signal proteins
US6512958B1 (en) 2001-04-26 2003-01-28 Medtronic, Inc. Percutaneous medical probe and flexible guide wire
US6974480B2 (en) 2001-05-03 2005-12-13 Synthes (Usa) Intervertebral implant for transforaminal posterior lumbar interbody fusion procedure
US6719794B2 (en) 2001-05-03 2004-04-13 Synthes (U.S.A.) Intervertebral implant for transforaminal posterior lumbar interbody fusion procedure
EP1408874B1 (en) 2001-06-14 2012-08-08 Amedica Corporation Metal-ceramic composite articulation
US6498421B1 (en) 2001-06-15 2002-12-24 Amega Lab, L.L.C. Ultrasonic drilling device with arc-shaped probe
US6558424B2 (en) 2001-06-28 2003-05-06 Depuy Acromed Modular anatomic fusion device
US20040220669A1 (en) 2001-06-27 2004-11-04 Armin Studer Intervertebral disk prosthesis
US7156877B2 (en) * 2001-06-29 2007-01-02 The Regents Of The University Of California Biodegradable/bioactive nucleus pulposus implant and method for treating degenerated intervertebral discs
US6607558B2 (en) 2001-07-03 2003-08-19 Axiomed Spine Corporation Artificial disc
US20030006942A1 (en) 2001-07-05 2003-01-09 Damion Searls Ergonomic auxiliary screen and display subsystem for portable handheld devices
WO2003005938A1 (en) 2001-07-12 2003-01-23 Osteotech, Inc. Intervertebral impant with movement resistant structure
US6987136B2 (en) 2001-07-13 2006-01-17 Vita Special Purpose Corporation Bioactive spinal implant material and method of manufacture thereof
US6468310B1 (en) 2001-07-16 2002-10-22 Third Millennium Engineering, Llc Intervertebral spacer device having a wave washer force restoring element
WO2003007780A2 (en) 2001-07-16 2003-01-30 Third Millenium Engineering Llc Artificial intervertebral disc having a wave washer force restoring element
US6428544B1 (en) 2001-07-16 2002-08-06 Third Millennium Engineering, Llc Insertion tool for use with trial intervertebral distraction spacers
US6676663B2 (en) 2001-07-19 2004-01-13 Higueras Antonio Perez Applicator device for controllably injecting a surgical cement into bones
WO2003007854A1 (en) 2001-07-20 2003-01-30 The Spineology Group, Llc Device for inserting fill material particles into body cavities
CN1835720B (en) 2001-07-25 2011-09-28 Disc整形外科技术股份有限公司 Deformable tools and implants
US6375682B1 (en) 2001-08-06 2002-04-23 Lewis W. Fleischmann Collapsible, rotatable and expandable spinal hydraulic prosthetic device
ES2211253B1 (en) 2001-08-16 2005-11-01 Industrias Quirurgicas De Levante, S.L. INTERSOMATIC CASE FOR BACK FUSION SURGERY OF THE LUMBAR COLUMN.
US7018412B2 (en) 2001-08-20 2006-03-28 Ebi, L.P. Allograft spinal implant
DE50114038D1 (en) 2001-08-24 2008-07-31 Zimmer Gmbh Artificial disc
EP1287794B1 (en) 2001-08-24 2008-06-18 Zimmer GmbH Artificial spinal disc
US20040024463A1 (en) 2001-08-27 2004-02-05 Thomas James C. Expandable implant for partial disc replacement and reinforcement of a disc partially removed in a discectomy and for reduction and maintenance of alignment of cancellous bone fractures and methods and apparatuses for same
US20030074075A1 (en) 2001-08-27 2003-04-17 Thomas James C. Expandable implant for partial disc replacement and reinforcement of a disc partially removed in a discectomy and for reduction and maintenance of alignment of cancellous bone fractures and methods and apparatuses for same
US7125421B2 (en) 2001-08-31 2006-10-24 Mitral Interventions, Inc. Method and apparatus for valve repair
US6656180B2 (en) 2001-09-05 2003-12-02 Stahurski Consulting Inc. Apparatus for retaining vertebrae in a desired spatial relationship
US6736815B2 (en) 2001-09-06 2004-05-18 Core Medical, Inc. Apparatus and methods for treating spinal discs
US20030050644A1 (en) 2001-09-11 2003-03-13 Boucher Ryan P. Systems and methods for accessing and treating diseased or fractured bone employing a guide wire
IN2014DN10834A (en) 2001-09-17 2015-09-04 Psivida Inc
US6955864B1 (en) 2001-09-21 2005-10-18 Defibtech, Llc Medical device battery pack with active status indication
WO2003026538A1 (en) 2001-09-27 2003-04-03 Sulzer Spine-Tech Inc. Modular spinal fusion device
WO2003026522A2 (en) 2001-09-28 2003-04-03 Sulzer Spine-Tech Inc. Skeletal stabilization implant
DE60232893D1 (en) 2001-10-02 2009-08-20 Rex Medical Lp EDDY IMPLANT
US6648917B2 (en) 2001-10-17 2003-11-18 Medicinelodge, Inc. Adjustable bone fusion implant and method
USD467657S1 (en) 2001-10-19 2002-12-24 Kyphon Inc. Hand held surgical instrument
USD469871S1 (en) 2001-10-19 2003-02-04 Kyphon Inc. Hand held surgical instrument
US6923936B2 (en) 2001-10-23 2005-08-02 Medtronic Minimed, Inc. Sterile device and method for producing same
US6923814B1 (en) 2001-10-30 2005-08-02 Nuvasive, Inc. System and methods for cervical spinal fusion
JP3993855B2 (en) 2001-11-01 2007-10-17 スパイン・ウェイブ・インコーポレーテッド Device for spinal disc recovery
DE10154163A1 (en) 2001-11-03 2003-05-22 Advanced Med Tech Device for straightening and stabilizing the spine
US8025684B2 (en) 2001-11-09 2011-09-27 Zimmer Spine, Inc. Instruments and methods for inserting a spinal implant
GB2382028B (en) 2001-11-19 2006-11-01 Aberdeen Orthopaedic Developme Intervertebral disc prosthesis
US7025787B2 (en) 2001-11-26 2006-04-11 Sdgi Holdings, Inc. Implantable joint prosthesis and associated instrumentation
US6979353B2 (en) 2001-12-03 2005-12-27 Howmedica Osteonics Corp. Apparatus for fusing adjacent bone structures
US6855167B2 (en) 2001-12-05 2005-02-15 Osteotech, Inc. Spinal intervertebral implant, interconnections for such implant and processes for making
US6758673B2 (en) 2001-12-05 2004-07-06 Ofir Fromovich Periosteal distraction
US7485134B2 (en) 2001-12-07 2009-02-03 Simonson Rush E Vertebral implants adapted for posterior insertion
MXPA04005707A (en) 2001-12-10 2005-06-20 Colbar Lifescience Ltd D Methods, devices, and preparations for intervertebral disc treatment.
CN1309350C (en) 2001-12-13 2007-04-11 华沙整形外科股份有限公司 Instrumentation and method for delivering an implant into a vertebral space
US20030171812A1 (en) 2001-12-31 2003-09-11 Ilan Grunberg Minimally invasive modular support implant device and method
US6764510B2 (en) 2002-01-09 2004-07-20 Myocor, Inc. Devices and methods for heart valve treatment
USD472323S1 (en) 2002-01-15 2003-03-25 Kyphon Inc. Hand-held mixer for flowable materials
US6893464B2 (en) 2002-03-05 2005-05-17 The Regents Of The University Of California Method and apparatus for providing an expandable spinal fusion cage
EP1482877B1 (en) 2002-03-11 2007-05-30 Spinal Concepts Inc. Instrumentation for implanting spinal implant devices
US6758862B2 (en) 2002-03-21 2004-07-06 Sdgi Holdings, Inc. Vertebral body and disc space replacement devices
US6726720B2 (en) 2002-03-27 2004-04-27 Depuy Spine, Inc. Modular disc prosthesis
BR0215679A (en) 2002-04-04 2005-02-01 Mathys Medizinaltechnik Ag Intervertebral prosthesis or core replacement prosthesis
US6966910B2 (en) 2002-04-05 2005-11-22 Stephen Ritland Dynamic fixation device and method of use
US20030195630A1 (en) 2002-04-10 2003-10-16 Ferree Bret A. Disc augmentation using materials that expand in situ
US20050261682A1 (en) 2002-04-13 2005-11-24 Ferree Bret A Vertebral shock absorbers
US7179294B2 (en) 2002-04-25 2007-02-20 Warsaw Orthopedic, Inc. Articular disc prosthesis and method for implanting the same
WO2003095026A1 (en) 2002-05-13 2003-11-20 Pflueger D Russell Spinal disc therapy system
US20040010318A1 (en) 2002-05-15 2004-01-15 Ferree Bret A. Conformable endplates for artificial disc replacement (ADR) devices and other applications
US6840944B2 (en) 2002-05-21 2005-01-11 Loubert Suddaby Vertebral body end plate cutter
CA2498962A1 (en) 2002-06-04 2003-12-11 Office Of Technology Licensing Stanford University Device and method for rapid aspiration and collection of body tissue from within an enclosed body space
US7273523B2 (en) 2002-06-07 2007-09-25 Kyphon Inc. Strontium-apatite-cement-preparations, cements formed therefrom, and uses thereof
WO2003105673A2 (en) 2002-06-17 2003-12-24 Trimedyne, Inc. Devices and methods for minimally invasive treatment of degenerated spinal discs
US6770095B2 (en) 2002-06-18 2004-08-03 Depuy Acroned, Inc. Intervertebral disc
US7070598B2 (en) 2002-06-25 2006-07-04 Sdgi Holdings, Inc. Minimally invasive expanding spacer and method
US7087055B2 (en) 2002-06-25 2006-08-08 Sdgi Holdings, Inc. Minimally invasive expanding spacer and method
US7582058B1 (en) 2002-06-26 2009-09-01 Nuvasive, Inc. Surgical access system and related methods
US6793678B2 (en) 2002-06-27 2004-09-21 Depuy Acromed, Inc. Prosthetic intervertebral motion disc having dampening
US7901407B2 (en) 2002-08-02 2011-03-08 Boston Scientific Scimed, Inc. Media delivery device for bone structures
CA2495373C (en) 2002-08-15 2012-07-24 David Gerber Controlled artificial intervertebral disc implant
DE60322066D1 (en) 2002-08-15 2008-08-21 Hfsc Co BAND DISC IMPLANT
US6863668B2 (en) 2002-08-16 2005-03-08 Edwards Lifesciences Corporation Articulation mechanism for medical devices
US20060293753A1 (en) 2002-08-19 2006-12-28 Lanx, Llc Corrective artificial disc
JP4495589B2 (en) 2002-08-27 2010-07-07 ウォーソー・オーソペディック・インコーポレーテッド System for intravertebral reduction
US20040087947A1 (en) 2002-08-28 2004-05-06 Roy Lim Minimally invasive expanding spacer and method
US20040087994A1 (en) 2002-08-29 2004-05-06 Loubert Suddaby Mechanical bone tamping device for repair of osteoporotic bone fractures
USD482787S1 (en) 2002-09-04 2003-11-25 Kyphon Inc. Hand held surgical instrument
DE10242984B4 (en) 2002-09-17 2010-09-23 Sanatis Gmbh Device for producing mixtures of two components
US20040054414A1 (en) 2002-09-18 2004-03-18 Trieu Hai H. Collagen-based materials and methods for augmenting intervertebral discs
CA2499116A1 (en) 2002-09-18 2004-04-01 Sdgi Holdings, Inc. Natural tissue devices and methods of implantation
US7744651B2 (en) 2002-09-18 2010-06-29 Warsaw Orthopedic, Inc Compositions and methods for treating intervertebral discs with collagen-based materials
US7074226B2 (en) 2002-09-19 2006-07-11 Sdgi Holdings, Inc. Oval dilator and retractor set and method
EP1542616B1 (en) 2002-09-20 2015-04-22 Endologix, Inc. Stent-graft with positioning anchor
US7018415B1 (en) 2002-09-23 2006-03-28 Sdgi Holdings, Inc. Expandable spinal fusion device and methods of promoting spinal fusion
US6899735B2 (en) 2002-10-02 2005-05-31 Sdgi Holdings, Inc. Modular intervertebral prosthesis system
USD490159S1 (en) 2002-10-04 2004-05-18 Kyphon Inc. Hand-held mixer for flowable materials
US7156876B2 (en) 2002-10-09 2007-01-02 Depuy Acromed, Inc. Intervertebral motion disc having articulation and shock absorption
IL152278A0 (en) 2002-10-14 2003-05-29 Expandis Ltd Minimally invasive support implant device and method
DE10248170A1 (en) 2002-10-16 2004-04-29 Advanced Medical Technologies Ag Implant for insertion between vertebras of a spinal column comprises two sides whose outer surfaces at the start of a vertebra spreading process converge towards the free ends of the sides
AU2003286531A1 (en) 2002-10-21 2004-05-13 3Hbfm, Llc Intervertebral disk prosthesis
US7267688B2 (en) 2002-10-22 2007-09-11 Ferree Bret A Biaxial artificial disc replacement
US20040186052A1 (en) 2002-10-24 2004-09-23 Suhasini Iyer Cytomodulating peptides and methods for treating neurological disorders
US20060264939A1 (en) 2003-05-22 2006-11-23 St. Francis Medical Technologies, Inc. Interspinous process implant with slide-in distraction piece and method of implantation
US8070778B2 (en) 2003-05-22 2011-12-06 Kyphon Sarl Interspinous process implant with slide-in distraction piece and method of implantation
US8048117B2 (en) 2003-05-22 2011-11-01 Kyphon Sarl Interspinous process implant and method of implantation
US7549999B2 (en) 2003-05-22 2009-06-23 Kyphon Sarl Interspinous process distraction implant and method of implantation
WO2004041131A2 (en) 2002-10-31 2004-05-21 Spinal Concepts, Inc. Movable disc implant
US6723126B1 (en) 2002-11-01 2004-04-20 Sdgi Holdings, Inc. Laterally expandable cage
US7828804B2 (en) 2002-11-08 2010-11-09 Warsaw Orthopedic, Inc. Transpedicular intervertebral disk access methods and devices
US20060147332A1 (en) 2004-12-30 2006-07-06 Howmedica Osteonics Corp. Laser-produced porous structure
KR20060079137A (en) 2002-11-08 2006-07-05 베르트링크 코오퍼레이션. Transpedicular intervertebral disk access methods and devices
US6685742B1 (en) 2002-11-12 2004-02-03 Roger P. Jackson Articulated anterior expandable spinal fusion cage system
UA79025C2 (en) 2002-11-13 2007-05-10 Смс Демаг Акцієнгезелльшафт Continuous casting mold for casting molten metals, particularly steel materials, at high casting rates to form polygonal billet, bloom, and preliminary section castings
US7320708B1 (en) 2002-11-13 2008-01-22 Sdgi Holdings, Inc. Cervical interbody device
JP2006507090A (en) 2002-11-21 2006-03-02 エスディージーアイ・ホールディングス・インコーポレーテッド System for intravertebral reduction
WO2004047689A1 (en) 2002-11-21 2004-06-10 Sdgi Holdings, Inc. Systems and techniques for intravertebral spinal stablization with expandable devices
WO2004047650A2 (en) 2002-11-23 2004-06-10 Sdgi Holdings, Inc. Istraction and retraction system for spinal surgery
US20050287071A1 (en) 2002-12-03 2005-12-29 Kyphon Inc. Formulation for a cement preparation as bone substitute
WO2004052245A1 (en) 2002-12-06 2004-06-24 Synthes Ag Chur Intervertebral implant
US20040186471A1 (en) 2002-12-07 2004-09-23 Sdgi Holdings, Inc. Method and apparatus for intervertebral disc expansion
US20040210310A1 (en) 2002-12-10 2004-10-21 Trieu Hai H. Implant system and method for intervertebral disc augmentation
US6974479B2 (en) 2002-12-10 2005-12-13 Sdgi Holdings, Inc. System and method for blocking and/or retaining a prosthetic spinal implant
US7204852B2 (en) 2002-12-13 2007-04-17 Spine Solutions, Inc. Intervertebral implant, insertion tool and method of inserting same
US20060122703A1 (en) 2002-12-17 2006-06-08 Max Aebi Intervertebral implant
US7004971B2 (en) 2002-12-31 2006-02-28 Depuy Acromed, Inc. Annular nucleus pulposus replacement
US20040133124A1 (en) 2003-01-06 2004-07-08 Cook Incorporated. Flexible biopsy needle
US20040133279A1 (en) 2003-01-06 2004-07-08 Krueger David J. Surgical implants for use as spinal spacers
US20040186577A1 (en) 2003-01-29 2004-09-23 Ferree Bret A. In situ artificaial disc replacements and other prosthetic components
US7828849B2 (en) 2003-02-03 2010-11-09 Warsaw Orthopedic, Inc. Expanding interbody implant and articulating inserter and method
USD492775S1 (en) 2003-02-12 2004-07-06 Kyphon Inc. Impact handle for hand held surgical instruments
USD495417S1 (en) 2003-02-12 2004-08-31 Kyphon Inc. Slip-fit handle for hand held surgical instruments
USD492032S1 (en) 2003-02-12 2004-06-22 Kyphon Inc. Impact handle for hand held surgical instruments
US7235101B2 (en) 2003-09-15 2007-06-26 Warsaw Orthopedic, Inc. Revisable prosthetic device
USD493533S1 (en) 2003-02-14 2004-07-27 Nuvasive, Inc. Intervertebral implant
US7094257B2 (en) 2003-02-14 2006-08-22 Zimmer Spine, Inc. Expandable intervertebral implant cage
US7276062B2 (en) 2003-03-12 2007-10-02 Biosence Webster, Inc. Deflectable catheter with hinge
WO2004082526A2 (en) 2003-03-14 2004-09-30 Schneiderman Gary A Intervertebral disk nuclear augmentation system
US20040186528A1 (en) 2003-03-20 2004-09-23 Medtronic, Inc. Subcutaneous implantable medical devices with anti-microbial agents for chronic release
US20040193274A1 (en) 2003-03-28 2004-09-30 Trieu Hai H. Materials and methods for augmenting and/or repairing intervertebral discs
IL155146A0 (en) 2003-03-30 2003-10-31 Expandis Ltd Minimally invasive distraction device and method
US7753912B2 (en) 2003-03-31 2010-07-13 Spine Wave, Inc. Tissue distraction device
US7517364B2 (en) 2003-03-31 2009-04-14 Depuy Products, Inc. Extended articulation orthopaedic implant and associated method
DE50308869D1 (en) 2003-04-14 2008-01-31 Synthes Gmbh INTERVERTEBRAL IMPLANT
US6969405B2 (en) 2003-04-23 2005-11-29 Loubert Suddaby Inflatable intervertebral disc replacement prosthesis
US6945973B2 (en) 2003-05-01 2005-09-20 Nuvasive, Inc. Slidable bone plate system
US20040220672A1 (en) 2003-05-03 2004-11-04 Shadduck John H. Orthopedic implants, methods of use and methods of fabrication
US7291173B2 (en) 2003-05-06 2007-11-06 Aesculap Ii, Inc. Artificial intervertebral disc
WO2004098420A2 (en) 2003-05-06 2004-11-18 Replication Medical, Inc. Fiber implant system for soft tissue augmentation
US20060206116A1 (en) 2003-05-07 2006-09-14 Yeung Jeffrey E Injection device for the invertebral disc
WO2004103152A2 (en) 2003-05-16 2004-12-02 Spine Wave, Inc. Tissue distraction device
DE10324108B3 (en) 2003-05-21 2005-01-27 Aesculap Ag & Co. Kg Backbone implant is inserted with contracted contact disc which is expanded to optimum area following insertion
US7575599B2 (en) 2004-07-30 2009-08-18 Spinalmotion, Inc. Intervertebral prosthetic disc with metallic core
ATE480203T1 (en) 2003-05-27 2010-09-15 Spinalmotion Inc INTERVERTEBRAL DISC PROSTHESIS FOR INTERVERTEBRAL INSERTION
US7270679B2 (en) 2003-05-30 2007-09-18 Warsaw Orthopedic, Inc. Implants based on engineered metal matrix composite materials having enhanced imaging and wear resistance
JP2006526480A (en) 2003-06-02 2006-11-24 エスディージーアイ・ホールディングス・インコーポレーテッド Intervertebral disc implants and methods for making and using them
US20040260300A1 (en) 2003-06-20 2004-12-23 Bogomir Gorensek Method of delivering an implant through an annular defect in an intervertebral disc
US7537612B2 (en) 2003-06-20 2009-05-26 Warsaw Orthopedic, Inc. Lumbar composite nucleus
US20040267367A1 (en) 2003-06-30 2004-12-30 Depuy Acromed, Inc Intervertebral implant with conformable endplate
US20050043796A1 (en) 2003-07-01 2005-02-24 Grant Richard L. Spinal disc nucleus implant
US7320689B2 (en) 2003-07-15 2008-01-22 Cervitech, Inc. Multi-part cervical endoprosthesis with insertion instrument
US7695515B2 (en) 2003-07-15 2010-04-13 Spinal Generations, Llc Spinal disc prosthesis system
US20050015148A1 (en) 2003-07-18 2005-01-20 Jansen Lex P. Biocompatible wires and methods of using same to fill bone void
US7758647B2 (en) 2003-07-25 2010-07-20 Impliant Ltd. Elastomeric spinal disc nucleus replacement
US7278970B2 (en) 2003-07-29 2007-10-09 Goldenberg Alec S Biopsy needles
US7022138B2 (en) 2003-07-31 2006-04-04 Mashburn M Laine Spinal interbody fusion device and method
US7806932B2 (en) 2003-08-01 2010-10-05 Zimmer Spine, Inc. Spinal implant
US8052723B2 (en) 2003-08-05 2011-11-08 Flexuspine Inc. Dynamic posterior stabilization systems and methods of use
US7316714B2 (en) 2003-08-05 2008-01-08 Flexuspine, Inc. Artificial functional spinal unit assemblies
US7753958B2 (en) 2003-08-05 2010-07-13 Gordon Charles R Expandable intervertebral implant
US7794476B2 (en) 2003-08-08 2010-09-14 Warsaw Orthopedic, Inc. Implants formed of shape memory polymeric material for spinal fixation
US7252686B2 (en) 2003-08-13 2007-08-07 Boston Scientific Scimed Methods for reducing bone compression fractures using wedges
US7226482B2 (en) 2003-09-02 2007-06-05 Synthes (U.S.A.) Multipiece allograft implant
AU2004270128B2 (en) 2003-09-03 2010-12-23 Kyphon Sarl Devices for creating voids in interior body regions and related methods
USD512506S1 (en) 2003-09-16 2005-12-06 Kyphon, Inc. Hand held surgical instrument for creating cavities in interior body regions
US20070043440A1 (en) 2003-09-19 2007-02-22 William Michael S Method and apparatus for treating diseased or fractured bone
USD506828S1 (en) 2003-09-23 2005-06-28 Kyphon Inc. Y-adapter
AU2003272683A1 (en) 2003-09-23 2005-05-11 Vanderbilt University Intervertebral disc replacement prosthesis
US7632294B2 (en) 2003-09-29 2009-12-15 Promethean Surgical Devices, Llc Devices and methods for spine repair
US7513900B2 (en) 2003-09-29 2009-04-07 Boston Scientific Scimed, Inc. Apparatus and methods for reducing compression bone fractures using high strength ribbed members
US7655010B2 (en) 2003-09-30 2010-02-02 Depuy Spine, Inc. Vertebral fusion device and method for using same
US7879102B2 (en) 2003-09-30 2011-02-01 Depuy Acromed, Inc. Method for treatment of defects in the intervertebral disc
US7731737B2 (en) 2003-10-24 2010-06-08 Zimmer Spine, Inc. Methods and apparatuses for fixation of the spine through an access device
US20050090899A1 (en) 2003-10-24 2005-04-28 Dipoto Gene Methods and apparatuses for treating the spine through an access device
DE20315611U1 (en) 2003-10-08 2003-12-11 Aesculap Ag & Co. Kg Intervertebral implant
US7840253B2 (en) 2003-10-17 2010-11-23 Medtronic Navigation, Inc. Method and apparatus for surgical navigation
DE102004021861A1 (en) 2004-05-04 2005-11-24 Biedermann Motech Gmbh Implant for temporary or permanent replacement of vertebra or intervertebral disk, comprising solid central element and outer elements with openings
WO2005037149A1 (en) 2003-10-20 2005-04-28 Impliant Ltd. Facet prosthesis
AU2004283727A1 (en) 2003-10-23 2005-05-06 Trans1 Inc. Tools and tool kits for performing minimally invasive procedures on the spine
WO2005041793A2 (en) 2003-10-23 2005-05-12 Trans1, Inc. Spinal mobility preservation apparatus and method
US20050124999A1 (en) 2003-10-31 2005-06-09 Teitelbaum George P. Device and method for radial delivery of a structural element
US20050119752A1 (en) 2003-11-19 2005-06-02 Synecor Llc Artificial intervertebral disc
DE60315037T2 (en) 2003-11-20 2008-04-24 Kyungwon Medical Co., Ltd. Expandable intervertebral fusion cage
US7217293B2 (en) 2003-11-21 2007-05-15 Warsaw Orthopedic, Inc. Expandable spinal implant
US6955691B2 (en) 2003-11-21 2005-10-18 Kyungwon Medical Co., Ltd. Expandable interfusion cage
US20050119751A1 (en) 2003-11-28 2005-06-02 Lawson Kevin J. Intervertebral bone fusion device
EP1705265B1 (en) 2003-12-04 2015-07-08 Nippon Steel & Sumitomo Metal Corporation Surface adjustment treatment prior to chemical treatment of steel product
US7217291B2 (en) 2003-12-08 2007-05-15 St. Francis Medical Technologies, Inc. System and method for replacing degenerated spinal disks
US20050125066A1 (en) 2003-12-08 2005-06-09 Innovative Spinal Technologies Nucleus replacement securing device and method
DE502004010737D1 (en) 2003-12-09 2010-03-25 Biedermann Motech Gmbh Height-adjustable intervertebral implant
DE20320974U1 (en) 2003-12-11 2005-08-25 Deltacor Gmbh Surgical backbone implant is positioned between adjacent vertebrae and consists of two concentric cylinders with interlocking fingers in cruciform array, where the cylinder inner faces bear a thread
US7569074B2 (en) 2003-12-11 2009-08-04 Warsaw Orthopedic, Inc. Expandable intervertebral implant
US7618427B2 (en) 2003-12-29 2009-11-17 Ethicon Endo-Surgery, Inc. Device and method for intralumenal anastomosis
US7018453B2 (en) 2003-12-31 2006-03-28 Sun Chemical Corporation Low VOC web offset heatset inks
US20050216087A1 (en) 2004-01-05 2005-09-29 St. Francis Medical Technologies, Inc. Disk repair structures for positioning disk repair material
WO2005070071A2 (en) 2004-01-08 2005-08-04 Spine Wave Inc. Apparatus and method for injecting fluent material at a distracted tissue site
US6952129B2 (en) 2004-01-12 2005-10-04 Ememory Technology Inc. Four-phase dual pumping circuit
US7250060B2 (en) 2004-01-27 2007-07-31 Sdgi Holdings, Inc. Hybrid intervertebral disc system
US7297146B2 (en) 2004-01-30 2007-11-20 Warsaw Orthopedic, Inc. Orthopedic distraction implants and techniques
US7211112B2 (en) 2004-02-10 2007-05-01 Atlas Spine Spinal fusion device
US7850733B2 (en) 2004-02-10 2010-12-14 Atlas Spine, Inc. PLIF opposing wedge ramp
US20050187556A1 (en) 2004-02-25 2005-08-25 Synecor, Llc Universal percutaneous spinal access system
EP1570813A1 (en) 2004-03-05 2005-09-07 Cervitech, Inc. Cervical intervertebral disc prosthesis with anti-luxation means, and instrument
US8636802B2 (en) 2004-03-06 2014-01-28 DePuy Synthes Products, LLC Dynamized interspinal implant
US8480742B2 (en) 2005-08-02 2013-07-09 Perumala Corporation Total artificial disc
US7214227B2 (en) 2004-03-22 2007-05-08 Innovative Spinal Technologies Closure member for a medical implant device
US7959634B2 (en) 2004-03-29 2011-06-14 Soteira Inc. Orthopedic surgery access devices
US7507241B2 (en) 2004-04-05 2009-03-24 Expanding Orthopedics Inc. Expandable bone device
US7465318B2 (en) 2004-04-15 2008-12-16 Soteira, Inc. Cement-directing orthopedic implants
US7789899B2 (en) 2004-12-30 2010-09-07 Warsaw Orthopedic, Inc. Bone anchorage screw with built-in hinged plate
US7811311B2 (en) 2004-12-30 2010-10-12 Warsaw Orthopedic, Inc. Screw with deployable interlaced dual rods
US7618418B2 (en) 2004-04-16 2009-11-17 Kyphon Sarl Plate system for minimally invasive support of the spine
US7648520B2 (en) 2004-04-16 2010-01-19 Kyphon Sarl Pedicle screw assembly
US7524323B2 (en) 2004-04-16 2009-04-28 Kyphon Sarl Subcutaneous support
US7452351B2 (en) 2004-04-16 2008-11-18 Kyphon Sarl Spinal diagnostic methods and apparatus
US7361179B2 (en) 2004-04-22 2008-04-22 Ethicon, Inc. Sternal closure device and method
US7322962B2 (en) 2004-04-23 2008-01-29 Leonard Edward Forrest Device and method for treatment of intervertebral disc disruption
WO2005105170A1 (en) 2004-04-27 2005-11-10 Kyphon Inc. Bone substitute compositions and method of use
US20050256576A1 (en) 2004-05-13 2005-11-17 Moskowitz Nathan C Artificial expansile total lumbar and thoracic discs for posterior placement without supplemental instrumentation and its adaptation for anterior placement of artificial cervical, thoracic and lumbar discs
US7854766B2 (en) 2004-05-13 2010-12-21 Moskowitz Nathan C Artificial total lumbar disc for unilateral safe and simple posterior placement in the lumbar spine, and removable bifunctional screw which drives vertical sliding expansile plate expansion, and interplate widening, and angled traction spikes
WO2005110259A1 (en) 2004-05-19 2005-11-24 Sintea Biotech S.P.A. Intravertebral widening device, injection device, and kit and method for kyphoplasty
US7621952B2 (en) 2004-06-07 2009-11-24 Dfine, Inc. Implants and methods for treating bone
US7344564B2 (en) 2004-06-08 2008-03-18 Spinal Generations, Llc Expandable spinal stabilization device
US20060095138A1 (en) 2004-06-09 2006-05-04 Csaba Truckai Composites and methods for treating bone
FR2871366A1 (en) 2004-06-09 2005-12-16 Ceravic Soc Par Actions Simpli PROSTHETIC EXPANSIBLE BONE IMPLANT
US20050278023A1 (en) 2004-06-10 2005-12-15 Zwirkoski Paul A Method and apparatus for filling a cavity
US20050278027A1 (en) 2004-06-11 2005-12-15 Hyde Edward R Jr Annulus fibrosus stent
US7556650B2 (en) 2004-06-29 2009-07-07 Spine Wave, Inc. Methods for injecting a curable biomaterial into an intervertebral space
CN101022770B (en) 2004-06-30 2012-02-08 辛纳吉椎间盘置换公司 Artificial spinal disc
EP1616540B1 (en) 2004-07-14 2007-11-14 BrainLAB AG Positioning system with cannulated implant
US7703727B2 (en) 2004-07-21 2010-04-27 Selness Jerry N Universal adjustable spacer assembly
US7651496B2 (en) 2004-07-23 2010-01-26 Zimmer Spine, Inc. Methods and apparatuses for percutaneous implant delivery
US7678148B2 (en) 2004-07-23 2010-03-16 Warsaw Orthopedic, Inc. Expandable spinal implant having interlocking geometry for structural support
EP1778134A1 (en) 2004-07-27 2007-05-02 Synthes USA Supplementation or replacement of a nucleus pulposus, of an intervertebral disc
US20060036259A1 (en) 2004-08-03 2006-02-16 Carl Allen L Spine treatment devices and methods
WO2006017714A2 (en) 2004-08-04 2006-02-16 Rebecca Delegge Thermal transition methods and devices
US20060085009A1 (en) 2004-08-09 2006-04-20 Csaba Truckai Implants and methods for treating bone
US8236029B2 (en) 2004-08-11 2012-08-07 Nlt Spine Ltd. Devices for introduction into a body via a substantially straight conduit to for a predefined curved configuration, and methods employing such devices
US20060036241A1 (en) 2004-08-11 2006-02-16 Tzony Siegal Spinal surgery system and method
US7503920B2 (en) 2004-08-11 2009-03-17 Tzony Siegal Spinal surgery system and method
CN101001587A (en) 2004-08-13 2007-07-18 斯恩蒂斯有限公司 Intervertebral implant
US20060036261A1 (en) 2004-08-13 2006-02-16 Stryker Spine Insertion guide for a spinal implant
US7905920B2 (en) 2004-08-19 2011-03-15 Foster-Miller, Inc. Support system for intervertebral fusion
US20060045904A1 (en) 2004-08-20 2006-03-02 Barry Aronson Joint therapy
US7875078B2 (en) 2004-08-25 2011-01-25 Spine Wave, Inc. Expandable interbody fusion device
US20060106459A1 (en) 2004-08-30 2006-05-18 Csaba Truckai Bone treatment systems and methods
FR2874814B1 (en) 2004-09-08 2007-11-16 Hassan Razian INTERVERTEBRAL CAGE
US7799081B2 (en) 2004-09-14 2010-09-21 Aeolin, Llc System and method for spinal fusion
WO2006034436A2 (en) 2004-09-21 2006-03-30 Stout Medical Group, L.P. Expandable support device and method of use
IL164260A0 (en) 2004-09-23 2005-12-18 Medigus Ltd An improved articulation section
US7481840B2 (en) 2004-09-29 2009-01-27 Kyphon Sarl Multi-piece artificial spinal disk replacement device with selectably positioning articulating element
US7575600B2 (en) 2004-09-29 2009-08-18 Kyphon Sarl Artificial vertebral disk replacement implant with translating articulation contact surface and method
US7682393B2 (en) 2004-10-14 2010-03-23 Warsaw Orthopedic, Inc. Implant system, method, and instrument for augmentation or reconstruction of intervertebral disc
US20080195096A1 (en) 2004-10-15 2008-08-14 The University Of British Columbia Orthopaedic Helical Coil Fastener and Apparatus and Method for Implantation Thereof
WO2006042487A1 (en) 2004-10-18 2006-04-27 Buettner-Janz Karin Intervertebral disc endoprosthesis having cylindrical articulation surfaces
US20060089719A1 (en) 2004-10-21 2006-04-27 Trieu Hai H In situ formation of intervertebral disc implants
AU2005299397A1 (en) 2004-10-25 2006-05-04 Alphaspine, Inc. Expandable intervertebral spacer method and apparatus
US9055981B2 (en) 2004-10-25 2015-06-16 Lanx, Inc. Spinal implants and methods
CA2614133A1 (en) 2004-10-25 2006-05-04 Lanx, Llc Interspinous distraction devices and associated methods of insertion
US7918875B2 (en) 2004-10-25 2011-04-05 Lanx, Inc. Interspinous distraction devices and associated methods of insertion
US20060155379A1 (en) 2004-10-25 2006-07-13 Heneveld Scott H Sr Expandable implant for repairing a defect in a nucleus of an intervertebral disc
US20060089646A1 (en) 2004-10-26 2006-04-27 Bonutti Peter M Devices and methods for stabilizing tissue and implants
US20060089642A1 (en) 2004-10-27 2006-04-27 Diaz Robert L Prefracture spinal implant for osteoporotic unfractured bone
US20060095134A1 (en) 2004-10-28 2006-05-04 Sdgi Holdings, Inc. Materials, devices and methods for implantation of transformable implants
US20060095045A1 (en) 2004-11-01 2006-05-04 Sdgi Holdings, Inc. Methods for explantation of intervertebral disc implants
US20060095136A1 (en) 2004-11-03 2006-05-04 Mcluen Design, Inc. Bone fusion device
US20060100706A1 (en) 2004-11-10 2006-05-11 Shadduck John H Stent systems and methods for spine treatment
CN101098667A (en) 2004-11-15 2008-01-02 光碟-O-特克医学科技有限公司 Assembled prosthesis such as a disc
US20060122701A1 (en) 2004-11-23 2006-06-08 Kiester P D Posterior lumbar interbody fusion expandable cage with lordosis and method of deploying the same
US7887589B2 (en) 2004-11-23 2011-02-15 Glenn Bradley J Minimally invasive spinal disc stabilizer and insertion tool
US20060149380A1 (en) 2004-12-01 2006-07-06 Lotz Jeffrey C Systems, devices and methods for treatment of intervertebral disorders
US8066749B2 (en) 2004-12-13 2011-11-29 Warsaw Orthopedic, Inc. Implant for stabilizing a bone graft during spinal fusion
WO2006066228A2 (en) 2004-12-16 2006-06-22 Innovative Spinal Technologies Expandable implants for spinal disc replacement
US20060136062A1 (en) 2004-12-17 2006-06-22 Dinello Alexandre Height-and angle-adjustable motion disc implant
US20060149136A1 (en) 2004-12-22 2006-07-06 Kyphon Inc. Elongating balloon device and method for soft tissue expansion
EP2633829B1 (en) 2005-01-05 2015-12-09 NLT Spine Ltd. Device for introduction into a body along a substantially straight elongated-element-restricting structure
JP2008526373A (en) 2005-01-08 2008-07-24 アルファスパイン インコーポレイテッド Modular disk device
US7655046B2 (en) 2005-01-20 2010-02-02 Warsaw Orthopedic, Inc. Expandable spinal fusion cage and associated instrumentation
DE102005004563B4 (en) 2005-02-01 2017-03-16 Advanced Medical Technologies Ag Spreadable implant for preferably dorsal arrangement between the vertebral bodies of the spine
US8083797B2 (en) 2005-02-04 2011-12-27 Spinalmotion, Inc. Intervertebral prosthetic disc with shock absorption
US7690381B2 (en) 2005-02-10 2010-04-06 Depuy Spine, Inc. Intervertebral prosthetic disc and method for installing using a guidewire
US20060184192A1 (en) 2005-02-11 2006-08-17 Markworth Aaron D Systems and methods for providing cavities in interior body regions
US20070055237A1 (en) 2005-02-17 2007-03-08 Edidin Avram A Percutaneous spinal implants and methods
US8038698B2 (en) 2005-02-17 2011-10-18 Kphon Sarl Percutaneous spinal implants and methods
US8100943B2 (en) 2005-02-17 2012-01-24 Kyphon Sarl Percutaneous spinal implants and methods
US7998174B2 (en) 2005-02-17 2011-08-16 Kyphon Sarl Percutaneous spinal implants and methods
US20060184248A1 (en) 2005-02-17 2006-08-17 Edidin Avram A Percutaneous spinal implants and methods
US7927354B2 (en) 2005-02-17 2011-04-19 Kyphon Sarl Percutaneous spinal implants and methods
US20060195102A1 (en) 2005-02-17 2006-08-31 Malandain Hugues F Apparatus and method for treatment of spinal conditions
US8029567B2 (en) 2005-02-17 2011-10-04 Kyphon Sarl Percutaneous spinal implants and methods
US7993342B2 (en) 2005-02-17 2011-08-09 Kyphon Sarl Percutaneous spinal implants and methods
US8057513B2 (en) 2005-02-17 2011-11-15 Kyphon Sarl Percutaneous spinal implants and methods
US20060265077A1 (en) 2005-02-23 2006-11-23 Zwirkoski Paul A Spinal repair
EP1858457B1 (en) 2005-02-24 2011-11-02 Morphogeny, LLC Linked slideable and interlockable rotatable components
CN101132748B (en) 2005-03-01 2010-06-16 斯拜恩塞尔有限公司 Intervertebral disc restoration
US7585324B2 (en) 2005-03-03 2009-09-08 Cervical Xpand, Llc Cervical intervertebral stabilizer
US8940048B2 (en) 2005-03-31 2015-01-27 Life Spine, Inc. Expandable spinal interbody and intravertebral body devices
US20060235423A1 (en) 2005-04-01 2006-10-19 Cantu Alberto R Apparatus having at least one actuatable planar surface and method using the same for a spinal procedure
US7959675B2 (en) 2005-04-08 2011-06-14 G&L Consulting, Llc Spine implant insertion device and method
US7942903B2 (en) 2005-04-12 2011-05-17 Moskowitz Ahmnon D Bi-directional fixating transvertebral body screws and posterior cervical and lumbar interarticulating joint calibrated stapling devices for spinal fusion
US9848993B2 (en) 2005-04-12 2017-12-26 Nathan C. Moskowitz Zero-profile expandable intervertebral spacer devices for distraction and spinal fusion and a universal tool for their placement and expansion
US8308802B2 (en) 2010-01-21 2012-11-13 Globus Medical, Inc. Expandable vertebral prosthesis
US20060241663A1 (en) 2005-04-21 2006-10-26 Zimmer Spine, Inc. Surgical cutter
US7674296B2 (en) 2005-04-21 2010-03-09 Globus Medical, Inc. Expandable vertebral prosthesis
US7799080B2 (en) 2005-04-22 2010-09-21 Doty Keith L Spinal disc prosthesis and methods of use
US7182783B2 (en) 2005-04-25 2007-02-27 Sdgi Holdings, Inc. Selectively expandable composite structures for spinal arthroplasty
JP5112295B2 (en) 2005-04-27 2013-01-09 スタウト メディカル グループ,エル.ピー. Expandable support and method of use
US20060247781A1 (en) 2005-04-29 2006-11-02 Sdgi Holdings, Inc. Implant
US7749270B2 (en) 2005-04-29 2010-07-06 Warsaw Orthopedic, Inc. Expandable intervertebral implant and associated instrumentation
FR2885032B1 (en) 2005-04-29 2007-07-27 Sdgi Holdings Inc KIT AND INSTRUMENTATION FOR EXECUTING A SPINAL IMPLANTATION PROCEDURE
AU2006242416A1 (en) 2005-05-02 2006-11-09 Seaspine, Inc. Motion restoring intervertebral device
CN102217983B (en) 2005-05-02 2013-01-30 活动脊柱技术有限公司 Intervertebral disc prosthesis
US7799083B2 (en) 2005-05-02 2010-09-21 Seaspine, Inc. Prosthesis for restoring motion in an appendage or spinal joint and an intervertebral spacer
US20060264896A1 (en) 2005-05-09 2006-11-23 Palmer Erika I Minimally invasive apparatus and method for treatment of a tumor associated with a bone
US8187327B2 (en) 2005-05-18 2012-05-29 Kyphon Sarl Selectively-expandable bone scaffold
DE102005022921B3 (en) 2005-05-19 2007-01-25 Aesculap Ag & Co. Kg Vertebral body replacement implant
US20070049849A1 (en) 2005-05-24 2007-03-01 Schwardt Jeffrey D Bone probe apparatus and method of use
US20060271196A1 (en) 2005-05-26 2006-11-30 Saal Jeffrey A Spinal disc annulus augmentation
WO2006130796A2 (en) 2005-06-02 2006-12-07 Zimmer Spine, Inc. Interbody fusion ring and method of using the same
US20060276899A1 (en) 2005-06-03 2006-12-07 Zipnick Richard I Minimally invasive apparatus to manipulate and revitalize spinal column disc
US7837688B2 (en) 2005-06-13 2010-11-23 Globus Medical Spinous process spacer
US7951199B2 (en) 2005-06-15 2011-05-31 Miller Jimmy D Lateral expandable interbody fusion cage
US7442210B2 (en) 2005-06-15 2008-10-28 Jerome Segal Mechanical apparatus and method for artificial disc replacement
US8021426B2 (en) 2005-06-15 2011-09-20 Ouroboros Medical, Inc. Mechanical apparatus and method for artificial disc replacement
US8080061B2 (en) 2005-06-20 2011-12-20 Synthes Usa, Llc Apparatus and methods for treating bone
US20070010889A1 (en) 2005-07-06 2007-01-11 Sdgi Holdings, Inc. Foldable nucleus replacement device
US20070078463A1 (en) 2005-07-07 2007-04-05 Malandain Hugues F Retractable cannula and method for minimally invasive medical procedure
US20070078436A1 (en) 2005-07-07 2007-04-05 Leung Andrea Y Balloon assisted apparatus and method for accessing an intervertebral disc
US20070010845A1 (en) 2005-07-08 2007-01-11 Gorman Gong Directionally controlled expandable device and methods for use
US20070010844A1 (en) 2005-07-08 2007-01-11 Gorman Gong Radiopaque expandable body and methods
US20070010824A1 (en) 2005-07-11 2007-01-11 Hugues Malandain Products, systems and methods for delivering material to bone and other internal body parts
EP1909658A2 (en) 2005-07-11 2008-04-16 Kyphon Inc. Systems and methods for providing cavities in interior body regions
US20070032703A1 (en) 2005-07-11 2007-02-08 Sankaran Meera L Radially expansive surgical instruments for tissue retraction and methods for using the same
US20070010848A1 (en) 2005-07-11 2007-01-11 Andrea Leung Systems and methods for providing cavities in interior body regions
US20070060935A1 (en) 2005-07-11 2007-03-15 Schwardt Jeffrey D Apparatus and methods of tissue removal within a spine
US8105236B2 (en) 2005-07-11 2012-01-31 Kyphon Sarl Surgical access device, system, and methods of use
EP1909671B1 (en) 2005-07-11 2012-01-18 Kyphon SÀRL System for inserting biocompatible filler materials in interior body regions
CA2614012A1 (en) 2005-07-11 2007-01-18 Kyphon Inc. Curette system
US20070006692A1 (en) 2005-07-11 2007-01-11 Phan Christopher U Torque limiting device
US7383639B2 (en) 2005-07-12 2008-06-10 Medtronic Spine Llc Measurement instrument for percutaneous surgery
WO2007009107A2 (en) 2005-07-14 2007-01-18 Stout Medical Group, P.L. Expandable support device and method of use
US20070032791A1 (en) 2005-07-14 2007-02-08 Greenhalgh E S Expandable support device and method of use
US7722674B1 (en) 2005-08-12 2010-05-25 Innvotec Surgical Inc. Linearly expanding spine cage for enhanced spinal fusion
CA2617872C (en) 2005-08-16 2013-12-24 Benvenue Medical, Inc. Spinal tissue distraction devices
US8454617B2 (en) 2005-08-16 2013-06-04 Benvenue Medical, Inc. Devices for treating the spine
US7651701B2 (en) 2005-08-29 2010-01-26 Sanatis Gmbh Bone cement composition and method of making the same
US20070067034A1 (en) 2005-08-31 2007-03-22 Chirico Paul E Implantable devices and methods for treating micro-architecture deterioration of bone tissue
US7731753B2 (en) 2005-09-01 2010-06-08 Spinal Kinetics, Inc. Prosthetic intervertebral discs
ES2292071T3 (en) 2005-09-06 2008-03-01 ORTHOPAEDIC & SPINE DEVELOPMENT DEFESTABLE PROTESIS OF SEPARATION OF VERTEBRAL BODIES.
US9028550B2 (en) 2005-09-26 2015-05-12 Coalign Innovations, Inc. Selectively expanding spine cage with enhanced bone graft infusion
CN101296669A (en) 2005-09-26 2008-10-29 华沙整形外科股份有限公司 Hybrid intervertebral spinal fusion implant
US8236058B2 (en) 2005-09-27 2012-08-07 Fabian Henry F Spine surgery method and implant
US9271843B2 (en) 2005-09-27 2016-03-01 Henry F. Fabian Spine surgery method and implant
US20070093899A1 (en) 2005-09-28 2007-04-26 Christof Dutoit Apparatus and methods for treating bone
US7879098B1 (en) 2005-10-19 2011-02-01 Simmons Jr James W Expandable lordosis stabilizing cage
US20070123989A1 (en) 2005-10-21 2007-05-31 Synthes (U.S.A.) Method and instruments to treat spondylolisthesis by an anterior minimally invasive approach of the spine
US20070093906A1 (en) 2005-10-26 2007-04-26 Zimmer Spine, Inc. Nucleus implant and method
WO2007062080A2 (en) 2005-11-21 2007-05-31 Philipp Lang Intervetebral devices and methods
US20070162127A1 (en) 2005-12-08 2007-07-12 Sdgi Holdings, Inc. Instruments and techniques for delivering non-rigid implant members in surgical procedures
KR20080081911A (en) 2005-12-08 2008-09-10 신세스 게엠바하 Apparatus and methods for treating bone
WO2007076376A2 (en) 2005-12-19 2007-07-05 Stout Medical Group, L.P. Expandable delivery device
WO2007076377A2 (en) 2005-12-19 2007-07-05 Stout Medical Group, L.P. Expandable support device
US20070150063A1 (en) 2005-12-22 2007-06-28 Depuy Spine, Inc. Devices for intervertebral augmentation and methods of controlling their delivery
US20070150059A1 (en) 2005-12-22 2007-06-28 Depuy Spine, Inc. Methods and devices for intervertebral augmentation using injectable formulations and enclosures
US20070150064A1 (en) 2005-12-22 2007-06-28 Depuy Spine, Inc. Methods and devices for intervertebral augmentation
US20070173939A1 (en) 2005-12-23 2007-07-26 The Board Of Trustees Of The Leland Stanford Junior University Systems and methods for fixation of bone with an expandable device
US8801790B2 (en) 2005-12-27 2014-08-12 Warsaw Orthopedic, Inc. Intervertebral disc augmentation and rehydration with superabsorbent polymers
US8506633B2 (en) 2005-12-27 2013-08-13 Warsaw Orthopedic, Inc. Rehydration and restoration of intervertebral discs with polyelectrolytes
WO2007084427A2 (en) 2006-01-13 2007-07-26 Anova Corporation Percutaneous cervical disc reconstruction
US20070168038A1 (en) 2006-01-13 2007-07-19 Sdgi Holdings, Inc. Materials, devices and methods for treating multiple spinal regions including the interbody region
US7799079B2 (en) 2006-01-18 2010-09-21 Zimmer Spine, Inc. Vertebral fusion device and method
US8083795B2 (en) 2006-01-18 2011-12-27 Warsaw Orthopedic, Inc. Intervertebral prosthetic device for spinal stabilization and method of manufacturing same
US7578849B2 (en) 2006-01-27 2009-08-25 Warsaw Orthopedic, Inc. Intervertebral implants and methods of use
US20070178222A1 (en) 2006-01-30 2007-08-02 Storey Daniel M Radiopaque coatings for polymer substrates
US7811326B2 (en) 2006-01-30 2010-10-12 Warsaw Orthopedic Inc. Posterior joint replacement device
US20070179618A1 (en) 2006-01-31 2007-08-02 Sdgi Holdings, Inc. Intervertebral prosthetic disc
US20070179615A1 (en) 2006-01-31 2007-08-02 Sdgi Holdings, Inc. Intervertebral prosthetic disc
US7708777B2 (en) 2006-02-03 2010-05-04 Depuy Spine, Inc. Modular intervertebral disc replacements
US20070213717A1 (en) 2006-02-14 2007-09-13 Sdgi Holdings, Inc. Biological fusion in the vertebral column
US20070208426A1 (en) 2006-03-03 2007-09-06 Sdgi Holdings, Inc. Spinal implant with improved surface properties for delivery
US8409290B2 (en) 2006-03-08 2013-04-02 Seaspine, Inc. Interbody device for spinal applications
US8262698B2 (en) 2006-03-16 2012-09-11 Warsaw Orthopedic, Inc. Expandable device for insertion between anatomical structures and a procedure utilizing same
US8282641B2 (en) 2006-03-28 2012-10-09 Depuy Spine, Inc. Methods and instrumentation for disc replacement
US20070233244A1 (en) 2006-03-28 2007-10-04 Depuy Spine, Inc. Artificial Disc Replacement Using Posterior Approach
DE202006005868U1 (en) 2006-04-06 2006-06-08 Aesculap Ag & Co. Kg Implant replacing intervertebral disk, comprising plates divided into movable segments lifted by expanding elements
AU2007238092A1 (en) 2006-04-12 2007-10-25 Spinalmotion, Inc. Posterior spinal device and method
US8366776B2 (en) 2006-04-13 2013-02-05 Warsaw Orthopedic, Inc. Vertebral implants having predetermined angular correction and method of use
US7981157B2 (en) 2006-04-27 2011-07-19 Warsaw Orthopedic, Inc. Self-contained expandable implant and method
EP2023864B1 (en) 2006-05-01 2019-07-10 Stout Medical Group, L.P. Expandable support device
US7708779B2 (en) 2006-05-01 2010-05-04 Warsaw Orthopedic, Inc. Expandable intervertebral spacers and methods of use
US20070260314A1 (en) 2006-05-02 2007-11-08 Ashok Biyani Transforaminal lumbar interbody fusion cage
US7842038B2 (en) 2006-05-04 2010-11-30 Warsaw Orthopedic, Inc. Method for using retractable stylet and cannula combination to form an opening in bone
US7771473B2 (en) 2006-07-06 2010-08-10 Lanx, Inc. Expandable spinal fusion cage
US20080009876A1 (en) 2006-07-07 2008-01-10 Meera Sankaran Medical device with expansion mechanism
US20080021556A1 (en) 2006-07-21 2008-01-24 Edie Jason A Expandable vertebral implant and methods of use
US20080021557A1 (en) 2006-07-24 2008-01-24 Warsaw Orthopedic, Inc. Spinal motion-preserving implants
US20080051902A1 (en) 2006-08-10 2008-02-28 James Dwyer Modular intervertebral disc prosthesis and method of replacing an intervertebral disc
US8057545B2 (en) 2006-08-25 2011-11-15 Warsaw Orthopedic, Inc. Revision spacer
US8506636B2 (en) 2006-09-08 2013-08-13 Theken Spine, Llc Offset radius lordosis
US8128700B2 (en) 2006-09-13 2012-03-06 Synthes Usa, Llc Allograft intervertebral implant and method of manufacturing the same
US8025697B2 (en) 2006-09-21 2011-09-27 Custom Spine, Inc. Articulating interbody spacer, vertebral body replacement
US8900306B2 (en) 2006-09-26 2014-12-02 DePuy Synthes Products, LLC Nucleus anti-expulsion devices and methods
US8641764B2 (en) 2006-10-11 2014-02-04 G&L Consulting, Llc Spine implant insertion device and method
GB0620400D0 (en) 2006-10-13 2006-11-22 Seddon Peter Spinal implant
US20080161927A1 (en) 2006-10-18 2008-07-03 Warsaw Orthopedic, Inc. Intervertebral Implant with Porous Portions
CA2668655A1 (en) 2006-11-16 2008-05-29 Rex Medical, L.P. Spinal implant and method of use
ES2339472T3 (en) 2006-11-23 2010-05-20 Biedermann Motech Gmbh EXPANSIBLE INTERVERTEBRAL IMPLANT.
AR064013A1 (en) 2006-11-30 2009-03-04 Paradigm Spine Llc VERTEBRAL, INTERLAMINAR, INTERESPINOUS STABILIZATION SYSTEM
WO2008070863A2 (en) 2006-12-07 2008-06-12 Interventional Spine, Inc. Intervertebral implant
US20080140085A1 (en) 2006-12-11 2008-06-12 G&L Consulting, Llc Steerable spine implant insertion device and method
US20080288077A1 (en) 2006-12-28 2008-11-20 Spinal Kinetics, Inc. Prosthetic Disc Assembly Having Natural Biomechanical Movement
US20080167657A1 (en) 2006-12-31 2008-07-10 Stout Medical Group, L.P. Expandable support device and method of use
US7947078B2 (en) 2007-01-09 2011-05-24 Nonlinear Technologies Ltd. Devices for forming curved or closed-loop structures
US7875059B2 (en) 2007-01-18 2011-01-25 Warsaw Orthopedic, Inc. Variable stiffness support members
US8377098B2 (en) 2007-01-19 2013-02-19 Flexuspine, Inc. Artificial functional spinal unit system and method for use
EP2124777A4 (en) 2007-02-21 2013-06-05 Benvenue Medical Inc Devices for treating the spine
US20080281425A1 (en) 2007-02-21 2008-11-13 John Thalgott Orthopaedic Implants and Prostheses
FR2913331B1 (en) 2007-03-05 2010-01-01 Hassan Razian INTERSOMATIC CAGE MAY BE INTERCALE BETWEEN TWO CONSECUTIVE VERTEBRAIS AND METHOD FOR FORMING THE SAME
US8021429B2 (en) 2007-03-08 2011-09-20 Zimmer Spine, Inc. Deployable segmented TLIF device
EP3300676A1 (en) 2007-03-12 2018-04-04 Stout Medical Group, L.P. Expandable attachment device
FR2914180B1 (en) 2007-03-28 2010-02-12 David Attia EXPANSIVE CAGE FOR VERTEBRAL SURGERY.
WO2008121312A2 (en) 2007-03-29 2008-10-09 Life Spine, Inc. Height adjustable spinal prostheses
WO2008121317A1 (en) 2007-03-29 2008-10-09 Life Spine, Inc. Radially expandable spinal interbody device and implantation tool
US8137401B2 (en) 2007-03-30 2012-03-20 Depuy Spine, Inc. Intervertebral device having expandable endplates
US8361154B2 (en) 2007-03-31 2013-01-29 Spinal Kinetics Inc. Temporarily bound prosthetic intervertebral discs implantable by minimally invasive surgical techniques
US9687353B2 (en) 2007-03-31 2017-06-27 Spinal Kinetics, Inc. Prosthetic intervertebral discs having balloon-based fillable cores that are implantable by minimally invasive surgical techniques
US20090069895A1 (en) 2007-03-31 2009-03-12 Spinal Kinetics, Inc. Prosthetic Intervertebral Discs Having Folding End Plates That Are Implantable By Minimally Invasive Surgical Techniques
US8795374B2 (en) 2007-04-01 2014-08-05 Spinal Kinetics Inc. Prosthetic intervertebral discs that are implantable by minimally invasive surgical techniques and that have cores that are insertable in situ using end plate guideways
US8163026B2 (en) 2007-04-05 2012-04-24 Zimmer Spine, Inc. Interbody implant
US8262666B2 (en) 2007-04-27 2012-09-11 Atlas Spine, Inc. Implantable distractor
US20100076559A1 (en) 2007-05-04 2010-03-25 Titan Spine, Llc Composite telescoping anterior interbody spinal implant
WO2008137192A1 (en) 2007-05-08 2008-11-13 Spinealign Medical, Inc. Systems, devices and methods for stabilizing bone
US8480715B2 (en) 2007-05-22 2013-07-09 Zimmer Spine, Inc. Spinal implant system and method
US7967867B2 (en) 2007-05-31 2011-06-28 Spine Wave, Inc. Expandable interbody fusion device
US8216312B2 (en) 2007-05-31 2012-07-10 Zimmer Spine, Inc. Spinal interbody system and method
US8900307B2 (en) 2007-06-26 2014-12-02 DePuy Synthes Products, LLC Highly lordosed fusion cage
US20090005873A1 (en) 2007-06-29 2009-01-01 Michael Andrew Slivka Spinous Process Spacer Hammock
ES2628055T3 (en) 2007-07-27 2017-08-01 R Tree Innovations, Llc Intercorporeal Implantation System
WO2009021144A2 (en) 2007-08-07 2009-02-12 Transcorp, Inc. Device for variably adjusting intervertebral distraction and lordosis
WO2009019669A1 (en) 2007-08-09 2009-02-12 Nonlinear Technologies Ltd. Device and method for spinous process distraction
EP2187843B1 (en) 2007-09-13 2015-10-07 DERU GmbH Endoprosthesis component
US8052754B2 (en) 2007-09-28 2011-11-08 Zimmer Gmbh Intervertebral endoprosthesis
US7850734B2 (en) 2007-10-10 2010-12-14 Custom Spine, Inc. Sliding intervertebral implant
WO2009055481A1 (en) 2007-10-22 2009-04-30 Spinalmotion, Inc. Dynamic spacer device and method for spanning a space formed upon removal of an intervertebral disc
US8267965B2 (en) 2007-10-22 2012-09-18 Flexuspine, Inc. Spinal stabilization systems with dynamic interbody devices
US8043381B2 (en) 2007-10-29 2011-10-25 Zimmer Spine, Inc. Minimally invasive interbody device and method
DE102007052042A1 (en) 2007-10-30 2009-05-14 Kilian Kraus Height-adjustable spine implant
US8182537B2 (en) 2007-10-30 2012-05-22 Aesculap Implant Systems, Llc Vertebral body replacement device and method for use to maintain a space between two vertebral bodies within a spine
WO2009064787A2 (en) 2007-11-12 2009-05-22 Synthes (U.S.A.) Adjustable height intervertebral implant
WO2009064847A2 (en) 2007-11-16 2009-05-22 Synthes (U.S.A.) Porous containment device and associated method for stabilization of vertebral compression fractures
WO2009070721A1 (en) 2007-11-28 2009-06-04 Pioneer Surgical Technology, Inc Device for securing an implant to tissue
US7799056B2 (en) 2007-12-31 2010-09-21 Warsaw Orthopedic, Inc. Bone fusion device and methods
US7985231B2 (en) 2007-12-31 2011-07-26 Kyphon Sarl Bone fusion device and methods
WO2009092030A1 (en) 2008-01-16 2009-07-23 Life Spine, Inc. Spinal inetrbody fusion cages providing variable anterior/posterior profieles
AU2009205896A1 (en) 2008-01-17 2009-07-23 Synthes Gmbh An expandable intervertebral implant and associated method of manufacturing the same
DE202008001079U1 (en) 2008-01-25 2008-03-27 Aesculap Ag & Co. Kg Intervertebral implant
EP2087857A1 (en) 2008-02-07 2009-08-12 K2M, Inc. Expandable vertebral device with cam lock
US8216314B2 (en) 2008-02-13 2012-07-10 Marc Richelsoph Distractable spinal implant assembly
US8323345B2 (en) 2008-02-14 2012-12-04 U.S. Spine, Inc. Anterior lumbar interbody fusion cage device and associated method
US20100145455A1 (en) 2008-12-10 2010-06-10 Innvotec Surgical, Inc. Lockable spinal implant
US8696751B2 (en) 2008-12-10 2014-04-15 Coalign Innovations, Inc. Adjustable distraction cage with linked locking mechanisms
US8267939B2 (en) 2008-02-28 2012-09-18 Stryker Spine Tool for implanting expandable intervertebral implant
US20090222096A1 (en) 2008-02-28 2009-09-03 Warsaw Orthopedic, Inc. Multi-compartment expandable devices and methods for intervertebral disc expansion and augmentation
US20090222099A1 (en) 2008-02-28 2009-09-03 Warsaw Orthopedics, Inc. Self Centering Nucleus Implant
JP5309163B2 (en) 2008-03-07 2013-10-09 ジンテス ゲゼルシャフト ミット ベシュレンクテル ハフツング Expandable interbody spacer device
CA2717800A1 (en) 2008-03-14 2009-09-17 Synthes Usa, Llc Nested expandable sleeve implant
EP2265200B1 (en) 2008-03-14 2020-05-27 Mazor Robotics Ltd. Segmented insert for intervertebral support
US20090240334A1 (en) 2008-03-19 2009-09-24 Richelsoph Marc E Vertebral device for restoration of vertebral body height
US8795365B2 (en) 2008-03-24 2014-08-05 Warsaw Orthopedic, Inc Expandable devices for emplacement in body parts and methods associated therewith
AU2009257987B2 (en) 2008-03-28 2014-04-03 K2M, Inc. Expandable cage
US20090248163A1 (en) 2008-03-31 2009-10-01 King Emily E Spinal surgery interbody
US8147555B2 (en) 2008-03-31 2012-04-03 Aflatoon Kamran Artificial disc prosthesis for replacing a damaged nucleus
BRPI0910325A8 (en) 2008-04-05 2019-01-29 Synthes Gmbh expandable intervertebral implant
US20090270873A1 (en) 2008-04-24 2009-10-29 Fabian Henry F Spine surgery method and inserter
CA2722048A1 (en) 2008-05-05 2009-11-12 Yves Arramon Polyaryletherketone artificial intervertebral disc
WO2009143496A1 (en) 2008-05-22 2009-11-26 Trinity Orthopedics, Llc Devices and methods for spinal reduction, displacement and resection
ES2361099B1 (en) 2008-05-26 2012-05-08 Rudolf Morgenstern Lopez "INTERVERTEBRAL PROSTHESIS"
WO2010003062A2 (en) 2008-07-03 2010-01-07 The Regents Of The University Of California Biomaterials and implants for enhanced cartilage formation, and methods for making and using them
EP2317939A1 (en) 2008-07-27 2011-05-11 Nonlinear Technologies Ltd. Tool and corresponding method for removal of material from within a body
US8328812B2 (en) 2008-07-27 2012-12-11 NLT-Spine Ltd. Tool and corresponding method for removal of material from within a body
US20100042218A1 (en) 2008-08-13 2010-02-18 Nebosky Paul S Orthopaedic implant with porous structural member
US9700431B2 (en) 2008-08-13 2017-07-11 Smed-Ta/Td, Llc Orthopaedic implant with porous structural member
US7927375B2 (en) 2008-09-12 2011-04-19 Doty Keith L Dynamic six-degrees-of-freedom intervertebral spinal disc prosthesis
WO2010045255A1 (en) 2008-10-14 2010-04-22 Praxis Powder Technology, Inc. Hybrid intervertebral spinal implant
US8545567B1 (en) 2008-11-14 2013-10-01 David Krueger Spinal fusion device
EP2199423B1 (en) 2008-12-16 2013-04-17 Sulzer Metco AG Thermally injected surface layer and orthopaedic implant
US8721723B2 (en) 2009-01-12 2014-05-13 Globus Medical, Inc. Expandable vertebral prosthesis
WO2010088766A1 (en) 2009-02-03 2010-08-12 National Research Council Of Canada Implant for total disc replacement, and method of forming
DE102009011648A1 (en) 2009-03-04 2010-09-09 Advanced Medical Technologies Ag Implant system with support elements
KR101657732B1 (en) 2009-03-12 2016-09-19 벡심 Apparatus for bone restoration of the spine and methods of use
EP2408382A4 (en) 2009-03-13 2013-06-19 Univ Toledo Minimally invasive collapsible cage
WO2010120782A2 (en) 2009-04-13 2010-10-21 Biospine, Llc Variable height intervertebral devices and methods for use
WO2010126915A1 (en) 2009-04-27 2010-11-04 Spinal Kinetics, Inc. Prosthetic intervertebral discs implantable by minimally invasive surgical techniques
US8382842B2 (en) 2009-05-14 2013-02-26 Stout Medical Group, L.P. Expandable support device and method of use
WO2010148112A1 (en) 2009-06-16 2010-12-23 Stout Medical Group, L.P. Expandable support device and method of use
KR20120047231A (en) 2009-06-17 2012-05-11 트리니티 올쏘피딕스, 엘엘씨 Expanding intervertebral device and methods of use
US20100324607A1 (en) 2009-06-23 2010-12-23 Davis Reginald J Pedicle screw with expansion anchor sleeve
EP2456396B1 (en) 2009-07-22 2017-09-13 Spinex Tec, LLC Apparatuses for vertebral body distraction and fusion employing a coaxial screw gear sleeve mechanism
WO2011046460A1 (en) 2009-10-14 2011-04-21 Manuel Laranjeira Gomes Dynamic biocompatible cage for replacing intervertebral disks of the vertebral column
WO2011046459A1 (en) 2009-10-14 2011-04-21 Manuel Laranjeira Gomes Adjustable device for replacing intervertebral disks of the vertebral column
US8556979B2 (en) 2009-10-15 2013-10-15 Globus Medical, Inc. Expandable fusion device and method of installation thereof
US9155628B2 (en) 2009-10-15 2015-10-13 Globus Medical, Inc. Expandable fusion device and method of installation thereof
US8685098B2 (en) 2010-06-25 2014-04-01 Globus Medical, Inc. Expandable fusion device and method of installation thereof
US8679183B2 (en) 2010-06-25 2014-03-25 Globus Medical Expandable fusion device and method of installation thereof
US8062375B2 (en) 2009-10-15 2011-11-22 Globus Medical, Inc. Expandable fusion device and method of installation thereof
US8709086B2 (en) 2009-10-15 2014-04-29 Globus Medical, Inc. Expandable fusion device and method of installation thereof
US8764806B2 (en) 2009-12-07 2014-07-01 Samy Abdou Devices and methods for minimally invasive spinal stabilization and instrumentation
US9393129B2 (en) 2009-12-10 2016-07-19 DePuy Synthes Products, Inc. Bellows-like expandable interbody fusion cage
AU2010339620A1 (en) 2009-12-30 2012-08-09 Spinal Usa, Inc. Spinal implant devices and methods
US8894712B2 (en) 2010-01-11 2014-11-25 Innova Spinal Technologies, Llc Expandable intervertebral implant and associated surgical method
US8795366B2 (en) 2010-01-11 2014-08-05 Innova Spinal Technologies, Llc Expandable intervertebral implant and associated surgical method
US8353963B2 (en) 2010-01-12 2013-01-15 Globus Medical Expandable spacer and method for use thereof
US8303879B2 (en) 2010-02-01 2012-11-06 Sb Technologies, Llc Composite interbody device and method of manufacture
JP5774028B2 (en) 2010-02-16 2015-09-02 エヌエルティー スパイン エルティーディー. Medical device locking mechanism
CZ2010155A3 (en) 2010-03-03 2011-09-14 Šrámek@Jirí Stand alone PLIF and TLIF cage for spinal column fusion with stability secured by threaded pins
WO2011119617A1 (en) 2010-03-22 2011-09-29 Seaspine, Inc. Spinal implant device, surgical instrumentation for implanting and method
US8591585B2 (en) 2010-04-12 2013-11-26 Globus Medical, Inc. Expandable vertebral implant
US9414923B2 (en) 2010-04-15 2016-08-16 Warsaw Orthopedic, Inc. Implant and method for producing an implant
US8540724B2 (en) 2010-04-30 2013-09-24 Lanx, Inc. Anterior distractor-inserter with linear countersink adjustment
US8535380B2 (en) 2010-05-13 2013-09-17 Stout Medical Group, L.P. Fixation device and method
WO2011142761A1 (en) 2010-05-13 2011-11-17 Stout Medical Group, L.P. Fixation device and method
EP2575691B1 (en) 2010-05-27 2015-12-30 Flexmedex, LLC Support device
US9827031B2 (en) 2010-05-28 2017-11-28 Benvenue Medical, Inc. Disc space sizing devices
US8506635B2 (en) 2010-06-02 2013-08-13 Warsaw Orthopedic, Inc. System and methods for a laterally expanding implant
US9597200B2 (en) 2010-06-25 2017-03-21 Globus Medical, Inc Expandable fusion device and method of installation thereof
AU2011271465B2 (en) 2010-06-29 2015-03-19 Synthes Gmbh Distractible intervertebral implant
US20160100954A1 (en) 2010-07-12 2016-04-14 Spinesmith Partners, L.P. Fusion device and associated methods
JP5807928B2 (en) 2010-07-15 2015-11-10 エヌエルティー スパイン エルティーディー. Surgical system and method for implanting expandable implants
EP3017793A3 (en) 2010-07-15 2016-08-17 Spine Wave, Inc. A plastically deformable inter-osseous device
US20120022653A1 (en) 2010-07-20 2012-01-26 X-Spine Systems, Inc. Composite orthopedic implant having a low friction material substrate with primary frictional features and secondary frictional features
CA2805476A1 (en) 2010-07-21 2012-01-26 Nlt Spine Ltd. Spinal surgery implants and delivery system
US8496706B2 (en) 2010-08-02 2013-07-30 Ashraf A. Ragab Bone cage with components for controlled expansion
US8778025B2 (en) 2010-08-02 2014-07-15 Ashraf A. Ragab Rotatable cam lift for an expandable bone cage
EP2608747A4 (en) 2010-08-24 2015-02-11 Flexmedex Llc Support device and method for use
WO2012030331A1 (en) 2010-09-01 2012-03-08 Smith & Nephew Orthopaedics Ag Fluent material delivery implant
WO2012028182A1 (en) 2010-09-01 2012-03-08 Smith & Nephew Orthopaedics Ag Orthopaedic implant system
US8845731B2 (en) 2010-09-03 2014-09-30 Globus Medical, Inc. Expandable fusion device and method of installation thereof
US8632595B2 (en) 2010-09-03 2014-01-21 Globus Medical, Inc. Expandable fusion device and method of installation thereof
US8845732B2 (en) 2010-09-03 2014-09-30 Globus Medical, Inc. Expandable fusion device and method of installation thereof
US8852279B2 (en) 2010-09-03 2014-10-07 Globus Medical, Inc. Expandable fusion device and method of installation thereof
US8398713B2 (en) 2010-09-03 2013-03-19 Globus Medical, Inc. Expandable fusion device and method of installation thereof
US8845734B2 (en) 2010-09-03 2014-09-30 Globus Medical, Inc. Expandable fusion device and method of installation thereof
US8435298B2 (en) 2010-09-03 2013-05-07 Globus Medical, Inc. Expandable fusion device and method of installation thereof
US9351848B2 (en) 2010-09-03 2016-05-31 Globus Medical, Inc. Expandable fusion device and method of installation thereof
US8491659B2 (en) 2010-09-03 2013-07-23 Globus Medical, Inc. Expandable fusion device and method of installation thereof
US20120071980A1 (en) 2010-09-16 2012-03-22 Alphatec Spine, Inc. Steerable spine implant and system
CN103687575B (en) 2010-10-05 2017-01-18 摩根·P·洛里奥 Intervertebral device and methods of use
EP2637582B1 (en) 2010-11-12 2017-08-23 Aesculap AG Spinal fixation system
US20120123546A1 (en) 2010-11-15 2012-05-17 MEDevice IP Holdings, LLC. Implant apparatus for spinal fusion
IT1403237B1 (en) 2010-12-29 2013-10-17 Mikai S P A PERCUTANEOUS DEVICE FOR TREATING VERTEBRAL FRACTURES
US8740980B2 (en) 2011-01-27 2014-06-03 Warsaw Orthopedic, Inc. Expandable medical implant
EP2693989B1 (en) 2011-02-14 2017-09-20 Imds Llc Expandable intervertebral implants
US8518087B2 (en) 2011-03-10 2013-08-27 Interventional Spine, Inc. Method and apparatus for minimally invasive insertion of intervertebral implants
AU2012236149B2 (en) 2011-03-30 2016-05-19 Trinity Orthopedics, Llc Articulating interbody cage and methods thereof
US8409291B2 (en) 2011-04-07 2013-04-02 Warsaw Orthopedic, Inc. Laterally expandable interbody spinal fusion implant
US8685095B2 (en) 2011-04-19 2014-04-01 Warsaw Orthopedic, Inc. Expandable implant system and methods of use
EP2517676B1 (en) 2011-04-29 2017-04-05 Medacta International S.A. Intervertebral implant for the fusion between two vertebral bodies of a vertebral column and corresponding positioning instrument
CA2835061A1 (en) 2011-05-12 2012-11-15 Nlt Spine Ltd. Tissue disruption device and corresponding methods
US9066813B2 (en) 2011-06-03 2015-06-30 Biomet Spine, Llc Unidirectional dynamic interbody fusion device and method of use
CN103826573B (en) 2011-07-05 2017-07-11 扩张整形外科公司 Bone structure utensil
WO2013023096A1 (en) 2011-08-09 2013-02-14 Neuropro Technologies, Inc. Bone fusion device, system and method
US9358123B2 (en) 2011-08-09 2016-06-07 Neuropro Spinal Jaxx, Inc. Bone fusion device, apparatus and method
JP6047571B2 (en) 2011-08-16 2016-12-21 ストライカー・スピン Expandable graft
US9427330B2 (en) 2011-09-06 2016-08-30 Globus Medical, Inc. Spinal plate
US9248028B2 (en) 2011-09-16 2016-02-02 DePuy Synthes Products, Inc. Removable, bone-securing cover plate for intervertebral fusion cage
US9561115B2 (en) 2011-09-20 2017-02-07 The University Of Toledo Expandable inter-vertebral cage and method of installing same
US8845728B1 (en) 2011-09-23 2014-09-30 Samy Abdou Spinal fixation devices and methods of use
US8864833B2 (en) 2011-09-30 2014-10-21 Globus Medical, Inc. Expandable fusion device and method of installation thereof
US9017410B2 (en) 2011-10-26 2015-04-28 Globus Medical, Inc. Artificial discs
US20130116791A1 (en) 2011-11-04 2013-05-09 Boo Holdings, Llc Expandable intervertebral spacer implant
US9526627B2 (en) 2011-11-17 2016-12-27 Exactech, Inc. Expandable interbody device system and method
EP2785284A4 (en) 2011-11-28 2015-08-05 Flexmedex Llc Support device and method for use
US9271777B2 (en) 2011-12-14 2016-03-01 Biomet Spine, Llc Unilateral moveable interbody fusion device and method of use
US9445919B2 (en) 2011-12-19 2016-09-20 Warsaw Orthopedic, Inc. Expandable interbody implant and methods of use
US8628578B2 (en) 2011-12-19 2014-01-14 Warsaw Orthopedic, Inc. Expandable interbody implant and methods of use
US20130190876A1 (en) 2012-01-19 2013-07-25 Warsaw Orthopedic, Inc. Expandable interbody implant and methods of use
US8778027B2 (en) 2012-01-23 2014-07-15 Medevice Ip Holdings, Llc Implant apparatus and method including tee and screw mechanism for spinal fusion
US8663329B2 (en) 2012-01-28 2014-03-04 Mark J Ernst Expandable implant for mammalian bony segment stabilization
JP6279488B2 (en) 2012-02-07 2018-02-14 ザ リージェンツ オブ ザ ユニバーシティ オブ カリフォルニア Products with nanostructures coated with tantalum and their fabrication and use
US9233007B2 (en) 2012-02-13 2016-01-12 Blue Tip Biologics, Llc Expandable self-anchoring interbody cage for orthopedic applications
ES2628444T3 (en) 2012-02-17 2017-08-02 Medacta International S.A. Intervertebral implant with improved clamping system for the fixation plate
US20130261746A1 (en) 2012-03-28 2013-10-03 Linares Medical Devices, Llc Implantable inter-vertebral disk having upper and lower layers of a metal exhibiting bone fusing characteristics and which sandwich therebetween a soft plastic cushioning disc for providing dynamic properties mimicking that of a natural inter-vertebral disc
WO2013158294A1 (en) 2012-04-16 2013-10-24 Biospine, Llc Multiple spindle adjustable interbody fusion devices and methods of use
AU2013262504B2 (en) 2012-05-18 2017-04-20 Trinity Orthopedics, Llc Articulating interbody cage and methods thereof
KR20150023455A (en) 2012-05-29 2015-03-05 엔엘티 스파인 리미티드. Laterally deflectable implant
WO2013184946A1 (en) 2012-06-06 2013-12-12 Medivest, Llc Expandable tissue spacer implant and method of use
US8843229B2 (en) 2012-07-20 2014-09-23 Biomet Manufacturing, Llc Metallic structures having porous regions from imaged bone at pre-defined anatomic locations
EP2877127B1 (en) 2012-07-26 2019-08-21 Synthes GmbH Expandable implant
WO2014026017A1 (en) 2012-08-08 2014-02-13 Robinson James C Percutaneuos cage delivery systems, devices and methods
US9532881B2 (en) 2012-08-12 2017-01-03 Brian Albert Hauck Memory material implant system and methods of use
US9226831B2 (en) 2012-08-27 2016-01-05 Globus Medical, Inc. Intervertebral implant
US9387087B2 (en) 2012-10-19 2016-07-12 Tyber Medical Llc Orthopedic systems for spine and tracking control
US9320617B2 (en) 2012-10-22 2016-04-26 Cogent Spine, LLC Devices and methods for spinal stabilization and instrumentation
US8715351B1 (en) 2012-11-29 2014-05-06 Spine Wave, Inc. Expandable interbody fusion device with graft chambers
WO2014088521A2 (en) 2012-12-06 2014-06-12 Kamil Bal Intervertebral expandable cage system and its instrument
US10299934B2 (en) 2012-12-11 2019-05-28 Globus Medical, Inc Expandable vertebral implant
US8663332B1 (en) 2012-12-13 2014-03-04 Ouroboros Medical, Inc. Bone graft distribution system
AR095189A1 (en) 2012-12-14 2015-09-30 Facet-Link Inc EXPANDABLE INTERVERTEBRAL BOX IN SCALED FORM
EP2948106B1 (en) 2013-01-24 2021-05-26 BioSpine, LLC Adjustable interbody fusion device
TWI571233B (en) 2013-02-08 2017-02-21 Stage - supported vertebral body fixation
US9204972B2 (en) 2013-03-01 2015-12-08 Globus Medical, Inc. Articulating expandable intervertebral implant
US9522070B2 (en) 2013-03-07 2016-12-20 Interventional Spine, Inc. Intervertebral implant
US10342675B2 (en) 2013-03-11 2019-07-09 Stryker European Holdings I, Llc Expandable implant
US9308090B2 (en) 2013-03-11 2016-04-12 DePuy Synthes Products, Inc. Coating for a titanium alloy substrate
US8900312B2 (en) 2013-03-12 2014-12-02 Spine Wave, Inc. Expandable interbody fusion device with graft chambers
US9358120B2 (en) 2013-03-14 2016-06-07 DePuy Synthes Products, Inc. Expandable coil spinal implant
US9480574B2 (en) 2013-03-14 2016-11-01 Benvenue Medical, Inc. Spinal fusion implants and devices and methods for deploying such implants
US8828085B1 (en) 2013-03-15 2014-09-09 Wade K. Jensen Hinged spinal insert device
CN114052999A (en) 2013-05-14 2022-02-18 扩展创新公司 Intervertebral device and related methods
US9456856B2 (en) 2013-09-26 2016-10-04 Warsaw Orthopedic, Inc. Intrabody osteotomy implant and methods of use
WO2015048997A1 (en) 2013-10-02 2015-04-09 Vigas Spinal implant for interbody use
US9782270B2 (en) 2014-08-08 2017-10-10 Warsaw Orthopedic, Inc. Spinal implant system and method
TWI548429B (en) 2014-11-07 2016-09-11 財團法人工業技術研究院 Medical composite material method for fabricating the same and applications thereof

Patent Citations (85)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2115250A (en) * 1936-05-28 1938-04-26 Rohm & Haas Organic nitrogen bases and their salts
US2170111A (en) * 1936-05-28 1939-08-22 Rohm & Haas Manufacture of amines
US2229024A (en) * 1939-05-23 1941-01-21 Rohm & Haas Aromatic ether of polyalkoxyalkylalkylene polyamines and process for obtaining them
US2706701A (en) * 1952-04-15 1955-04-19 Gen Aniline & Film Corp Process for the preparation of iodinepolyvinylpyrrolidone by dry mixing
US2826532A (en) * 1952-04-15 1958-03-11 Gen Aniline & Film Corp Process of stabilizing polyvinyl pyrrolidone-iodine compositions
US2900305A (en) * 1952-04-15 1959-08-18 Gen Aniline & Film Corp Preparation of iodine polyvinylpyrrolidone adducts
US2710277A (en) * 1952-04-23 1955-06-07 West Laboratories Inc Iodine phosphate ester compositions
US2977315A (en) * 1956-09-12 1961-03-28 Lazarus Lab Inc Water soluble iodine-phosphoric-acidsynthetic detergent composition
US3228828A (en) * 1963-02-15 1966-01-11 Standard Naphthalene Products Insecticide composition comprising naphthalene and paraffinic hydrocarbon
US3717655A (en) * 1968-08-19 1973-02-20 Janssen Pharmaceutica Nv 1-(beta-aryl)ethyl-imidazole derivatives
US3936466A (en) * 1974-04-01 1976-02-03 Interx Research Corporation 3-Chloro-tetrahydro-1,3-oxazines or oxazolidines spiro substituted
US4352883A (en) * 1979-03-28 1982-10-05 Damon Corporation Encapsulation of biological material
US4440921A (en) * 1982-06-21 1984-04-03 Research Corporation Coupling of polyorganophosphazenes to carboxylic acid
US4495174A (en) * 1982-06-21 1985-01-22 Research Corporation Anesthetic polyorganophosphazenes
US4645503A (en) * 1985-08-27 1987-02-24 Orthomatrix Inc. Moldable bone-implant material
US4743256A (en) * 1985-10-04 1988-05-10 Brantigan John W Surgical prosthetic implant facilitating vertebral interbody fusion and method
US4686607A (en) * 1986-01-08 1987-08-11 Teradyne, Inc. Daughter board/backplane assembly
US5133755A (en) * 1986-01-28 1992-07-28 Thm Biomedical, Inc. Method and apparatus for diodegradable, osteogenic, bone graft substitute device
US4880622A (en) * 1986-05-20 1989-11-14 Research Corporation Technologies, Inc. Water-soluble phosphazene polymers having pharmacological applications
US4964814A (en) * 1986-10-03 1990-10-23 Minnesota Mining And Manufacturing Co. Shielded and grounded connector system for coaxial cables
US4772287A (en) * 1987-08-20 1988-09-20 Cedar Surgical, Inc. Prosthetic disc and method of implanting
US4943245A (en) * 1989-07-31 1990-07-24 Microdot Inc. Coaxial electrical connector
US6203565B1 (en) * 1990-06-28 2001-03-20 Peter M. Bonutti Surgical devices assembled using heat bondable materials
US5410016A (en) * 1990-10-15 1995-04-25 Board Of Regents, The University Of Texas System Photopolymerizable biodegradable hydrogels as tissue contacting materials and controlled-release carriers
US6197325B1 (en) * 1990-11-27 2001-03-06 The American National Red Cross Supplemented and unsupplemented tissue sealants, methods of their production and use
US5192327A (en) * 1991-03-22 1993-03-09 Brantigan John W Surgical prosthetic implant for vertebrae
US5176538A (en) * 1991-12-13 1993-01-05 W. L. Gore & Associates, Inc. Signal interconnector module and assembly thereof
US5441424A (en) * 1993-04-15 1995-08-15 Framatome Connectors International Connector for coaxial and/or twinaxial cables
US5522895A (en) * 1993-07-23 1996-06-04 Rice University Biodegradable bone templates
US5775947A (en) * 1993-07-27 1998-07-07 Japan Aviation Electronics Industry, Limited Multi-contact connector with cross-talk blocking elements between signal contacts
US5443514A (en) * 1993-10-01 1995-08-22 Acromed Corporation Method for using spinal implants
US5397364A (en) * 1993-10-12 1995-03-14 Danek Medical, Inc. Anterior interbody fusion device
US6306177B1 (en) * 1994-05-06 2001-10-23 Advanced Bio Surfaces, Inc. Biomaterial system for in situ tissue repair
US6248131B1 (en) * 1994-05-06 2001-06-19 Advanced Bio Surfaces, Inc. Articulating joint repair
US5888220A (en) * 1994-05-06 1999-03-30 Advanced Bio Surfaces, Inc. Articulating joint repair
US5549679A (en) * 1994-05-20 1996-08-27 Kuslich; Stephen D. Expandable fabric implant for stabilizing the spinal motion segment
US6187048B1 (en) * 1994-05-24 2001-02-13 Surgical Dynamics, Inc. Intervertebral disc implant
US5562736A (en) * 1994-10-17 1996-10-08 Raymedica, Inc. Method for surgical implantation of a prosthetic spinal disc nucleus
US5679723A (en) * 1994-11-30 1997-10-21 Ethicon, Inc. Hard tissue bone cements and substitutes
US6224894B1 (en) * 1995-03-06 2001-05-01 Ethicon, Inc. Copolymers of absorbable polyoxaesters
US6214368B1 (en) * 1995-05-19 2001-04-10 Etex Corporation Bone substitution material and a method of its manufacture
US6331312B1 (en) * 1995-05-19 2001-12-18 Etex Corporation Bioresorbable ceramic composites
US5833657A (en) * 1995-05-30 1998-11-10 Ethicon, Inc. Single-walled balloon catheter with non-linear compliance characteristic
US5702449A (en) * 1995-06-07 1997-12-30 Danek Medical, Inc. Reinforced porous spinal implants
US6113624A (en) * 1995-10-02 2000-09-05 Ethicon, Inc. Absorbable elastomeric polymer
US5888227A (en) * 1995-10-20 1999-03-30 Synthes (U.S.A.) Inter-vertebral implant
US5807327A (en) * 1995-12-08 1998-09-15 Ethicon, Inc. Catheter assembly
US5824084A (en) * 1996-07-03 1998-10-20 The Cleveland Clinic Foundation Method of preparing a composite bone graft
US5766036A (en) * 1996-10-11 1998-06-16 Molex Incorporated Impedance matched cable assembly having latching subassembly
US5775924A (en) * 1996-10-11 1998-07-07 Molex Incorporated Modular terminating connector with frame ground
US6123550A (en) * 1996-12-13 2000-09-26 Fuba Automotive Gmbh & Co Kg Line plug connection
US20010039452A1 (en) * 1997-01-02 2001-11-08 St. Francis Medical Technologies, Inc. Spine distraction implant and method
US6280474B1 (en) * 1997-01-09 2001-08-28 Neucoll, Inc. Devices for tissue repair and methods for preparation and use thereof
US5972385A (en) * 1997-01-15 1999-10-26 Orquest, Inc. Collagen-polysaccharide matrix for bone and cartilage repair
US6071982A (en) * 1997-04-18 2000-06-06 Cambridge Scientific, Inc. Bioerodible polymeric semi-interpenetrating network alloys for surgical plates and bone cements, and method for making same
US5800549A (en) * 1997-04-30 1998-09-01 Howmedica Inc. Method and apparatus for injecting an elastic spinal implant
US5837752A (en) * 1997-07-17 1998-11-17 Massachusetts Institute Of Technology Semi-interpenetrating polymer networks
US20010039453A1 (en) * 1997-08-13 2001-11-08 Gresser Joseph D. Resorbable interbody spinal fusion devices
US5971770A (en) * 1997-11-05 1999-10-26 Labinal Components And Systems, Inc. Coaxial connector with bellows spring portion or raised bump
US6562072B1 (en) * 1998-01-23 2003-05-13 Aesculap Ag & Co. Kg Implant for insertion between spinal column vertebrae
US6171610B1 (en) * 1998-04-24 2001-01-09 University Of Massachusetts Guided development and support of hydrogel-cell compositions
US6146202A (en) * 1998-08-12 2000-11-14 Robinson Nugent, Inc. Connector apparatus
US6165486A (en) * 1998-11-19 2000-12-26 Carnegie Mellon University Biocompatible compositions and methods of using same
US6147135A (en) * 1998-12-31 2000-11-14 Ethicon, Inc. Fabrication of biocompatible polymeric composites
US6113638A (en) * 1999-02-26 2000-09-05 Williams; Lytton A. Method and apparatus for intervertebral implant anchorage
US6805697B1 (en) * 1999-05-07 2004-10-19 University Of Virginia Patent Foundation Method and system for fusing a spinal region
US6264695B1 (en) * 1999-09-30 2001-07-24 Replication Medical, Inc. Spinal nucleus implant
US6592625B2 (en) * 1999-10-20 2003-07-15 Anulex Technologies, Inc. Spinal disc annulus reconstruction method and spinal disc annulus stent
US6203369B1 (en) * 1999-10-25 2001-03-20 3M Innovative Properties Company High frequency cable connector having low self-inductance ground return paths
US20020055781A1 (en) * 1999-12-23 2002-05-09 John A. Sazy Intervertebral cage and method of use
US20020058947A1 (en) * 2000-02-28 2002-05-16 Stephen Hochschuler Method and apparatus for treating a vertebral body
US6332894B1 (en) * 2000-03-07 2001-12-25 Zimmer, Inc. Polymer filled spinal fusion cage
US6494883B1 (en) * 2000-05-26 2002-12-17 Bret A. Ferree Bone reinforcers
US20020198526A1 (en) * 2000-06-23 2002-12-26 Shaolian Samuel M. Formed in place fixation system with thermal acceleration
US6478624B2 (en) * 2000-06-29 2002-11-12 Robinson Nugent, Inc. High speed connector
US20020193883A1 (en) * 2001-01-25 2002-12-19 Wironen John F. Injectable porous bone graft materials
US6368351B1 (en) * 2001-03-27 2002-04-09 Bradley J. Glenn Intervertebral space implant for use in spinal fusion procedures
US6632235B2 (en) * 2001-04-19 2003-10-14 Synthes (U.S.A.) Inflatable device and method for reducing fractures in bone and in treating the spine
US20110098818A1 (en) * 2001-05-01 2011-04-28 Brodke Darrel S Radiolucent spinal fusion cage
US20030028251A1 (en) * 2001-07-30 2003-02-06 Mathews Hallett H. Methods and devices for interbody spinal stabilization
US20040049270A1 (en) * 2002-09-10 2004-03-11 Gewirtz Robert J. Bone graft device
US6979352B2 (en) * 2002-11-21 2005-12-27 Depuy Acromed Methods of performing embolism-free vertebroplasty and devices therefor
US7500991B2 (en) * 2002-12-31 2009-03-10 Depuy Acromed, Inc. Banana cage
US20040127990A1 (en) * 2002-12-31 2004-07-01 Bartish, Charles M. Novel banana cage
US20120310352A1 (en) * 2003-02-14 2012-12-06 Depuy Spine, Inc. In-situ intervertebral fusion device and method

Cited By (708)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9668875B2 (en) 1999-03-07 2017-06-06 Nuvasive, Inc. Method and apparatus for computerized surgery
US7717958B2 (en) * 2000-02-16 2010-05-18 Trans1, Inc. Prosthetic nucleus apparatus
US20050113919A1 (en) * 2000-02-16 2005-05-26 Cragg Andrew H. Prosthetic nucleus apparatus
US7905908B2 (en) 2000-02-16 2011-03-15 Trans1, Inc. Spinal mobility preservation method
US7905905B2 (en) 2000-02-16 2011-03-15 Trans1, Inc. Spinal mobility preservation apparatus
US7662173B2 (en) 2000-02-16 2010-02-16 Transl, Inc. Spinal mobility preservation apparatus
US7727262B2 (en) 2000-06-23 2010-06-01 Warsaw Orthopedic, Inc. Formed in place fixation system with thermal acceleration
US8083774B2 (en) 2000-06-23 2011-12-27 Warsaw Orthopedic, Inc. Percutaneous vertebral fusion system
US8337556B2 (en) 2000-06-23 2012-12-25 Sdgi Holdings, Inc. Curable media for implantable medical device
US7833249B2 (en) 2000-06-23 2010-11-16 Warsaw Orthopedic, Inc. Formable orthopedic fixation system
US20100114107A1 (en) * 2000-08-30 2010-05-06 Warsaw Orthopedic, Inc. Intervertebral Disc Nucleus Implants and Methods
US20090234457A1 (en) * 2001-06-29 2009-09-17 The Regents Of The University Of California Systems, devices and methods for treatment of intervertebral disorders
US20080009944A1 (en) * 2001-10-02 2008-01-10 Rex Medical Spinal implant and method of use
US9095449B2 (en) 2001-10-02 2015-08-04 Rex Medical, L. P. Method of inserting a spinal implant
US10238500B2 (en) 2002-06-27 2019-03-26 DePuy Synthes Products, Inc. Intervertebral disc
US9993349B2 (en) 2002-06-27 2018-06-12 DePuy Synthes Products, Inc. Intervertebral disc
US8435301B2 (en) 2002-08-15 2013-05-07 DePuy Synthes Products, LLC Artificial intervertebral disc implant
US8523918B2 (en) 2002-12-03 2013-09-03 Baxano Surgical, Inc. Therapy to adjacent motion segments
US8328847B2 (en) 2002-12-03 2012-12-11 Trans1 Inc. Assemblies for provision of therapy to motion segments
US8167947B2 (en) 2002-12-03 2012-05-01 Trans1 Inc. Methods for push distraction and for provision of therapy to adjacent motion segments
US7776042B2 (en) 2002-12-03 2010-08-17 Trans1 Inc. Methods and apparatus for provision of therapy to adjacent motion segments
US10433971B2 (en) 2003-02-14 2019-10-08 DePuy Synthes Products, Inc. In-situ formed intervertebral fusion device and method
US10639164B2 (en) 2003-02-14 2020-05-05 DePuy Synthes Products, Inc. In-situ formed intervertebral fusion device and method
US9801729B2 (en) 2003-02-14 2017-10-31 DePuy Synthes Products, Inc. In-situ formed intervertebral fusion device and method
US10405986B2 (en) 2003-02-14 2019-09-10 DePuy Synthes Products, Inc. In-situ formed intervertebral fusion device and method
US10420651B2 (en) 2003-02-14 2019-09-24 DePuy Synthes Products, Inc. In-situ formed intervertebral fusion device and method
US11432938B2 (en) 2003-02-14 2022-09-06 DePuy Synthes Products, Inc. In-situ intervertebral fusion device and method
US9333091B2 (en) 2003-02-14 2016-05-10 DePuy Synthes Products, Inc. In-situ formed intervertebral fusion device and method
US9808351B2 (en) 2003-02-14 2017-11-07 DePuy Synthes Products, Inc. In-situ formed intervertebral fusion device and method
US9814590B2 (en) 2003-02-14 2017-11-14 DePuy Synthes Products, Inc. In-situ formed intervertebral fusion device and method
US10492918B2 (en) 2003-02-14 2019-12-03 DePuy Synthes Products, Inc. In-situ formed intervertebral fusion device and method
US10376372B2 (en) 2003-02-14 2019-08-13 DePuy Synthes Products, Inc. In-situ formed intervertebral fusion device and method
US10085843B2 (en) 2003-02-14 2018-10-02 DePuy Synthes Products, Inc. In-situ formed intervertebral fusion device and method
US10555817B2 (en) 2003-02-14 2020-02-11 DePuy Synthes Products, Inc. In-situ formed intervertebral fusion device and method
US10575959B2 (en) 2003-02-14 2020-03-03 DePuy Synthes Products, Inc. In-situ formed intervertebral fusion device and method
US10786361B2 (en) 2003-02-14 2020-09-29 DePuy Synthes Products, Inc. In-situ formed intervertebral fusion device and method
US9439777B2 (en) 2003-02-14 2016-09-13 DePuy Synthes Products, Inc. In-situ formed intervertebral fusion device and method
US9439776B2 (en) 2003-02-14 2016-09-13 DePuy Synthes Products, Inc. In-situ formed intervertebral fusion device and method
US9925060B2 (en) 2003-02-14 2018-03-27 DePuy Synthes Products, Inc. In-situ formed intervertebral fusion device and method
US11207187B2 (en) 2003-02-14 2021-12-28 DePuy Synthes Products, Inc. In-situ formed intervertebral fusion device and method
US9788963B2 (en) 2003-02-14 2017-10-17 DePuy Synthes Products, Inc. In-situ formed intervertebral fusion device and method
US10583013B2 (en) 2003-02-14 2020-03-10 DePuy Synthes Products, Inc. In-situ formed intervertebral fusion device and method
US9724207B2 (en) 2003-02-14 2017-08-08 DePuy Synthes Products, Inc. In-situ formed intervertebral fusion device and method
US9814589B2 (en) 2003-02-14 2017-11-14 DePuy Synthes Products, Inc. In-situ formed intervertebral fusion device and method
US9730803B2 (en) 2003-02-14 2017-08-15 DePuy Synthes Products, Inc. Method of in-situ formation of an intervertebral fusion device
US11096794B2 (en) 2003-02-14 2021-08-24 DePuy Synthes Products, Inc. In-situ formed intervertebral fusion device and method
US8992541B2 (en) 2003-03-14 2015-03-31 DePuy Synthes Products, LLC Hydraulic device for the injection of bone cement in percutaneous vertebroplasty
US10799278B2 (en) 2003-03-14 2020-10-13 DePuy Synthes Products, Inc. Hydraulic device for the injection of bone cement in percutaneous vertebroplasty
US9186194B2 (en) 2003-03-14 2015-11-17 DePuy Synthes Products, Inc. Hydraulic device for the injection of bone cement in percutaneous vertebroplasty
US9839460B2 (en) 2003-03-31 2017-12-12 DePuy Synthes Products, Inc. Remotely-activated vertebroplasty injection device
US10485597B2 (en) 2003-03-31 2019-11-26 DePuy Synthes Products, Inc. Remotely-activated vertebroplasty injection device
US8333773B2 (en) 2003-03-31 2012-12-18 Depuy Spine, Inc. Remotely-activated vertebroplasty injection device
US8066713B2 (en) 2003-03-31 2011-11-29 Depuy Spine, Inc. Remotely-activated vertebroplasty injection device
US20110067703A1 (en) * 2003-04-29 2011-03-24 Mallinckrodt Inc. Medical device with antimicrobial layer
US20040220534A1 (en) * 2003-04-29 2004-11-04 Martens Paul W. Medical device with antimicrobial layer
US10039585B2 (en) 2003-06-17 2018-08-07 DePuy Synthes Products, Inc. Methods, materials and apparatus for treating bone and other tissue
US8956368B2 (en) 2003-06-17 2015-02-17 DePuy Synthes Products, LLC Methods, materials and apparatus for treating bone and other tissue
US8540722B2 (en) 2003-06-17 2013-09-24 DePuy Synthes Products, LLC Methods, materials and apparatus for treating bone and other tissue
US8361078B2 (en) 2003-06-17 2013-01-29 Depuy Spine, Inc. Methods, materials and apparatus for treating bone and other tissue
US9504508B2 (en) 2003-06-17 2016-11-29 DePuy Synthes Products, Inc. Methods, materials and apparatus for treating bone and other tissue
US9592258B2 (en) 2003-06-27 2017-03-14 DePuy Synthes Products, Inc. Treatment of neurological injury by administration of human umbilical cord tissue-derived cells
US10433974B2 (en) 2003-06-30 2019-10-08 DePuy Synthes Products, Inc. Intervertebral implant with conformable endplate
US11612493B2 (en) 2003-06-30 2023-03-28 DePuy Synthes Products, Inc. Intervertebral implant with conformable endplate
US8579908B2 (en) 2003-09-26 2013-11-12 DePuy Synthes Products, LLC. Device for delivering viscous material
US10111697B2 (en) 2003-09-26 2018-10-30 DePuy Synthes Products, Inc. Device for delivering viscous material
US8372152B2 (en) 2003-09-30 2013-02-12 X-Spine Systems, Inc. Spinal fusion system utilizing an implant plate having at least one integral lock and ratchet lock
US8795370B2 (en) 2003-09-30 2014-08-05 X-Spine Systems, Inc. Fusion system and method for fusing spinal bones
US8282682B2 (en) 2003-09-30 2012-10-09 X-Spine Systems, Inc. Fusion system and method for fusing spinal bones
US8821553B2 (en) 2003-09-30 2014-09-02 X-Spine Systems, Inc. Spinal fusion system utilizing an implant plate having at least one integral lock
US7655028B2 (en) 2003-09-30 2010-02-02 X-Spine Systems, Inc. Spinal fusion system and method for fusing spinal bones
US9078706B2 (en) 2003-09-30 2015-07-14 X-Spine Systems, Inc. Intervertebral fusion device utilizing multiple mobile uniaxial and bidirectional screw interface plates
US8062367B2 (en) 2003-09-30 2011-11-22 X-Spine Systems, Inc. Screw locking mechanism and method
US20050113923A1 (en) * 2003-10-03 2005-05-26 David Acker Prosthetic spinal disc nucleus
US20070168036A1 (en) * 2003-10-23 2007-07-19 Trans1 Inc. Spinal motion preservation assemblies
US20080004707A1 (en) * 2003-10-23 2008-01-03 Cragg Andrew H Prosthetic nucleus apparatus and method
US20070167951A1 (en) * 2003-10-23 2007-07-19 Trans1 Inc. Methods and tools for delivery of spinal motion preservation assemblies
US20060155297A1 (en) * 2003-10-23 2006-07-13 Ainsworth Stephen D Driver assembly for simultaneous axial delivery of spinal implants
US7601171B2 (en) 2003-10-23 2009-10-13 Trans1 Inc. Spinal motion preservation assemblies
US8038680B2 (en) 2003-10-23 2011-10-18 Trans1 Inc. Drivers for inserts to bone anchors
US20060206209A1 (en) * 2003-10-23 2006-09-14 Cragg Andrew H Prosthetic nucleus apparatus and methods
US20060079898A1 (en) * 2003-10-23 2006-04-13 Trans1 Inc. Spinal motion preservation assemblies
US7776068B2 (en) 2003-10-23 2010-08-17 Trans1 Inc. Spinal motion preservation assemblies
US7938836B2 (en) 2003-10-23 2011-05-10 Trans1, Inc. Driver assembly for simultaneous axial delivery of spinal implants
US20080195156A1 (en) * 2003-10-23 2008-08-14 Trans1 Inc. Methods for Deploying Spinal Motion Preservation Assemblies
US20050187140A1 (en) * 2003-11-20 2005-08-25 Angiotech International Ag Polymer compositions and methods for their use
US8765165B2 (en) 2003-12-11 2014-07-01 Zimmer, Inc. Particulate cartilage system
US8834914B2 (en) 2003-12-11 2014-09-16 Zimmer, Inc. Treatment methods using a particulate cadaveric allogenic juvenile cartilage particles
US8524268B2 (en) 2003-12-11 2013-09-03 Zimmer, Inc. Cadaveric allogenic human juvenile cartilage implant
US8784863B2 (en) 2003-12-11 2014-07-22 Zimmer, Inc. Particulate cadaveric allogenic cartilage system
US8518433B2 (en) 2003-12-11 2013-08-27 Zimmer, Inc. Method of treating an osteochondral defect
US8652507B2 (en) 2003-12-11 2014-02-18 Zimmer, Inc. Juvenile cartilage composition
US8415407B2 (en) 2004-03-21 2013-04-09 Depuy Spine, Inc. Methods, materials, and apparatus for treating bone and other tissue
US9750840B2 (en) 2004-03-21 2017-09-05 DePuy Synthes Products, Inc. Methods, materials and apparatus for treating bone and other tissue
US8809418B2 (en) 2004-03-21 2014-08-19 DePuy Synthes Products, LLC Methods, materials and apparatus for treating bone and other tissue
US20060004358A1 (en) * 2004-06-30 2006-01-05 Depuy Spine, Inc. In-situ formed posterolateral fusion system
US7776073B2 (en) * 2004-06-30 2010-08-17 Depuy Spine, Inc. In-situ formed posterolateral fusion system
US9402859B1 (en) 2004-07-08 2016-08-02 Reva Medical, Inc. Devices, compositions and methods for bone and tissue augmentation
US10143493B2 (en) 2004-07-08 2018-12-04 Reva Medical, Inc. Devices, compositions and methods for bone and tissue augmentation
US8110003B2 (en) * 2004-09-09 2012-02-07 University Of South Florida Prostheses for spine discs having fusion capability
US8540771B2 (en) 2004-09-09 2013-09-24 University Of South Florida Prostheses for spine discs having fusion capability
US20060052874A1 (en) * 2004-09-09 2006-03-09 Johnson Wesley M Prostheses for spine discs having fusion capability
US20060089652A1 (en) * 2004-10-26 2006-04-27 Concept Matrix, Llc Working channel for minimally invasive spine surgery
US20100081884A1 (en) * 2004-10-26 2010-04-01 Concept Matrix, Llc Working Channel for Minimally Invasive Spine Surgery
US7651499B2 (en) 2004-10-26 2010-01-26 Concept Matrix, Llc Working channel for minimally invasive spine surgery
US8206292B2 (en) 2004-10-26 2012-06-26 Concept Matrix, Llc Working channel for minimally invasive spine surgery
US10682240B2 (en) 2004-11-03 2020-06-16 Neuropro Technologies, Inc. Bone fusion device
US9974665B2 (en) 2004-11-03 2018-05-22 Neuropro Technologies, Inc. Bone fusion device
US11583414B2 (en) 2004-11-03 2023-02-21 Neuropro Technologies, Inc. Bone fusion device
US20060106461A1 (en) * 2004-11-12 2006-05-18 Embry Jill M Implantable vertebral lift
US7799078B2 (en) * 2004-11-12 2010-09-21 Warsaw Orthopedic, Inc. Implantable vertebral lift
US10918498B2 (en) 2004-11-24 2021-02-16 Samy Abdou Devices and methods for inter-vertebral orthopedic device placement
US11096799B2 (en) 2004-11-24 2021-08-24 Samy Abdou Devices and methods for inter-vertebral orthopedic device placement
WO2006060482A3 (en) * 2004-12-01 2007-02-22 Univ California Systems, devices and methods of treatment of intervertebral disorders
EP1816990A4 (en) * 2004-12-01 2009-10-14 Univ California Systems, devices and methods for treatment of intervertebral disorders
US20060149380A1 (en) * 2004-12-01 2006-07-06 Lotz Jeffrey C Systems, devices and methods for treatment of intervertebral disorders
EP1816990A2 (en) * 2004-12-01 2007-08-15 The Regents of the University of California Systems, devices and methods for treatment of intervertebral disorders
US20070078477A1 (en) * 2005-02-04 2007-04-05 Heneveld Scott H Sr Anatomical spacer and method to deploy
US20090259177A1 (en) * 2005-02-16 2009-10-15 Susan Lynn Riley Resorbable hollow devices for implantation and delivery of therapeutic agents
US9662152B2 (en) * 2005-02-16 2017-05-30 Nuvasive, Inc. Resorbable hollow devices for implantation and delivery of therapeutic agents
US20060265077A1 (en) * 2005-02-23 2006-11-23 Zwirkoski Paul A Spinal repair
US20060200245A1 (en) * 2005-03-07 2006-09-07 Sdgi Holdings, Inc. Materials, devices, and methods for in-situ formation of composite intervertebral implants
US20060217810A1 (en) * 2005-03-24 2006-09-28 Toussaint Leclercq Artifical lumbar disc
US7632312B2 (en) * 2005-03-24 2009-12-15 Neurocare International, Inc. Artifical lumbar disc
WO2006111174A1 (en) * 2005-04-16 2006-10-26 Aesculap Ag & Co. Kg Implant for alleviating pressure on intervertebral disks and method for the adjustment and pressure alleviation of an intervertebral space
US20080109082A1 (en) * 2005-04-16 2008-05-08 Ulrich Fink Implant for alleviating pressure on intervertebral disks and method for restoring the height of and alleviating pressure on an intervertebral space
EP2272470A3 (en) * 2005-04-29 2011-01-26 Warsaw Orthopedic, Inc. Synthetic loadbearing collagen-mineral composites for spinal implants
WO2006118803A3 (en) * 2005-04-29 2007-07-26 Warsaw Orthopedic Inc Synthetic loadbearing collagen-mineral composites for spinal implants
US20060247625A1 (en) * 2005-04-29 2006-11-02 Sdgi Holdings, Inc. System, devices and method for augmenting existing fusion constructs
US7695499B2 (en) 2005-04-29 2010-04-13 Warsaw Orthopedic, Inc. System, devices and method for augmenting existing fusion constructs
US20100198265A1 (en) * 2005-04-29 2010-08-05 Morrison Matthew M System, Devices and method for augmenting existing fusion constructs
US20060247783A1 (en) * 2005-04-30 2006-11-02 Mckay William F Spinal fusion with osteogenic material and migration barrier
US8162992B2 (en) * 2005-04-30 2012-04-24 Warsaw Orthopedic, Inc. Spinal fusion with osteogenic material and migration barrier
US20110213402A1 (en) * 2005-05-24 2011-09-01 Kyphon Sarl Low-compliance expandable medical device
US20090104586A1 (en) * 2005-06-01 2009-04-23 Osseous Technologies Of America Collagen Antral Membrane Expander
US7988735B2 (en) * 2005-06-15 2011-08-02 Matthew Yurek Mechanical apparatus and method for delivering materials into the inter-vertebral body space for nucleus replacement
US20060287730A1 (en) * 2005-06-15 2006-12-21 Jerome Segal Mechanical apparatus and method for artificial disc replacement
US20060287727A1 (en) * 2005-06-15 2006-12-21 Jerome Segal Mechanical apparatus and method for artificial disc replacement
US7442210B2 (en) * 2005-06-15 2008-10-28 Jerome Segal Mechanical apparatus and method for artificial disc replacement
US7547319B2 (en) * 2005-06-15 2009-06-16 Ouroboros Medical Mechanical apparatus and method for artificial disc replacement
US20090136576A1 (en) * 2005-06-20 2009-05-28 Giuseppe Calvosa Biocompatible composition for replacing/regenerating tissues
US20070021835A1 (en) * 2005-07-11 2007-01-25 Edidin Avram A Systems and methods for providing prostheses
US20070027544A1 (en) * 2005-07-28 2007-02-01 Altiva Corporation Spinal cage implant
US9381024B2 (en) 2005-07-31 2016-07-05 DePuy Synthes Products, Inc. Marked tools
US9918767B2 (en) 2005-08-01 2018-03-20 DePuy Synthes Products, Inc. Temperature control system
US8591583B2 (en) * 2005-08-16 2013-11-26 Benvenue Medical, Inc. Devices for treating the spine
US7785368B2 (en) 2005-08-16 2010-08-31 Benvenue Medical, Inc. Spinal tissue distraction devices
US8882836B2 (en) 2005-08-16 2014-11-11 Benvenue Medical, Inc. Apparatus and method for treating bone
US7670374B2 (en) 2005-08-16 2010-03-02 Benvenue Medical, Inc. Methods of distracting tissue layers of the human spine
US7955391B2 (en) 2005-08-16 2011-06-07 Benvenue Medical, Inc. Methods for limiting the movement of material introduced between layers of spinal tissue
US8961609B2 (en) 2005-08-16 2015-02-24 Benvenue Medical, Inc. Devices for distracting tissue layers of the human spine
US9259326B2 (en) 2005-08-16 2016-02-16 Benvenue Medical, Inc. Spinal tissue distraction devices
US8454617B2 (en) 2005-08-16 2013-06-04 Benvenue Medical, Inc. Devices for treating the spine
US8808376B2 (en) * 2005-08-16 2014-08-19 Benvenue Medical, Inc. Intravertebral implants
US10028840B2 (en) 2005-08-16 2018-07-24 Izi Medical Products, Llc Spinal tissue distraction devices
US7963993B2 (en) 2005-08-16 2011-06-21 Benvenue Medical, Inc. Methods of distracting tissue layers of the human spine
US7967865B2 (en) 2005-08-16 2011-06-28 Benvenue Medical, Inc. Devices for limiting the movement of material introduced between layers of spinal tissue
US7967864B2 (en) 2005-08-16 2011-06-28 Benvenue Medical, Inc. Spinal tissue distraction devices
US8556978B2 (en) 2005-08-16 2013-10-15 Benvenue Medical, Inc. Devices and methods for treating the vertebral body
US20090182386A1 (en) * 2005-08-16 2009-07-16 Laurent Schaller Spinal tissue distraction devices
US8979929B2 (en) 2005-08-16 2015-03-17 Benvenue Medical, Inc. Spinal tissue distraction devices
US8801787B2 (en) 2005-08-16 2014-08-12 Benvenue Medical, Inc. Methods of distracting tissue layers of the human spine
US7670375B2 (en) 2005-08-16 2010-03-02 Benvenue Medical, Inc. Methods for limiting the movement of material introduced between layers of spinal tissue
US8366773B2 (en) 2005-08-16 2013-02-05 Benvenue Medical, Inc. Apparatus and method for treating bone
US20070123986A1 (en) * 2005-08-16 2007-05-31 Laurent Schaller Methods of Distracting Tissue Layers of the Human Spine
US9788974B2 (en) 2005-08-16 2017-10-17 Benvenue Medical, Inc. Spinal tissue distraction devices
US9066808B2 (en) 2005-08-16 2015-06-30 Benvenue Medical, Inc. Method of interdigitating flowable material with bone tissue
US9326866B2 (en) 2005-08-16 2016-05-03 Benvenue Medical, Inc. Devices for treating the spine
US8057544B2 (en) * 2005-08-16 2011-11-15 Benvenue Medical, Inc. Methods of distracting tissue layers of the human spine
US7666226B2 (en) 2005-08-16 2010-02-23 Benvenue Medical, Inc. Spinal tissue distraction devices
US7666227B2 (en) 2005-08-16 2010-02-23 Benvenue Medical, Inc. Devices for limiting the movement of material introduced between layers of spinal tissue
US9044338B2 (en) 2005-08-16 2015-06-02 Benvenue Medical, Inc. Spinal tissue distraction devices
US8480757B2 (en) 2005-08-26 2013-07-09 Zimmer, Inc. Implants and methods for repair, replacement and treatment of disease
US8025903B2 (en) 2005-09-09 2011-09-27 Wright Medical Technology, Inc. Composite bone graft substitute cement and articles produced therefrom
US8685465B2 (en) 2005-09-09 2014-04-01 Agnovos Healthcare, Llc Composite bone graft substitute cement and articles produced therefrom
US8685464B2 (en) 2005-09-09 2014-04-01 Agnovos Healthcare, Llc Composite bone graft substitute cement and articles produced therefrom
US9180224B2 (en) 2005-09-09 2015-11-10 Agnovos Healthcare, Llc Composite bone graft substitute cement and articles produced therefrom
US7754246B2 (en) 2005-09-09 2010-07-13 Wright Medical Technology, Inc. Composite bone graft substitute cement and articles produced therefrom
US20070067036A1 (en) * 2005-09-20 2007-03-22 Zimmer Spine, Inc. Hydrogel total disc prosthesis
US8062373B2 (en) 2005-09-27 2011-11-22 Fabian Jr Henry F Spine surgery method and motion preserving implant
US8236058B2 (en) 2005-09-27 2012-08-07 Fabian Henry F Spine surgery method and implant
US20070073398A1 (en) * 2005-09-27 2007-03-29 Fabian Henry F Spine surgery method and implant
US9271843B2 (en) 2005-09-27 2016-03-01 Henry F. Fabian Spine surgery method and implant
US20070093899A1 (en) * 2005-09-28 2007-04-26 Christof Dutoit Apparatus and methods for treating bone
US9005296B2 (en) * 2005-09-30 2015-04-14 Arthrodisc, L.L.C. Tapered arcuate intervertebral implant
US20120330417A1 (en) * 2005-09-30 2012-12-27 Arthrodisc, L.L.C. Tapered arcuate intervertebral implant
US9408875B2 (en) 2005-10-12 2016-08-09 Lifenet Health Compositions for repair of defects in tissues, and methods of making the same
US8197545B2 (en) 2005-10-27 2012-06-12 Depuy Spine, Inc. Nucleus augmentation delivery device and technique
US9162041B2 (en) 2005-10-27 2015-10-20 DePuy Synthes Products, Inc. Nucleus augmentation delivery device and technique
US8357199B2 (en) 2005-10-27 2013-01-22 Depuy Spine, Inc. Nucleus augmentation delivery device and technique
US20070173935A1 (en) * 2005-10-28 2007-07-26 O'neil Michael J Nucleus pulposus augmentation pretreatment technique
US20090060972A1 (en) * 2005-11-21 2009-03-05 Nicast Ltd. Device and method for cell grafting
US9259696B2 (en) 2005-11-22 2016-02-16 DePuy Synthes Products, Inc. Mixing apparatus having central and planetary mixing elements
US10631906B2 (en) 2005-11-22 2020-04-28 DePuy Synthes Products, Inc. Apparatus for transferring a viscous material
US8360629B2 (en) 2005-11-22 2013-01-29 Depuy Spine, Inc. Mixing apparatus having central and planetary mixing elements
US20070118218A1 (en) * 2005-11-22 2007-05-24 Hooper David M Facet joint implant and procedure
US11406508B2 (en) 2005-12-23 2022-08-09 DePuy Synthes Products, Inc. Flexible elongated chain implant and method of supporting body tissue with same
US7723422B2 (en) 2005-12-23 2010-05-25 Boston Scientific Scimed, Inc. Functionalized block copolymers
US11701233B2 (en) 2005-12-23 2023-07-18 DePuy Synthes Products, Inc. Flexible elongated chain implant and method of supporting body tissue with same
US10881520B2 (en) 2005-12-23 2021-01-05 DePuy Synthes Products, Inc. Flexible elongated chain implant and method of supporting body tissue with same
US9289240B2 (en) 2005-12-23 2016-03-22 DePuy Synthes Products, Inc. Flexible elongated chain implant and method of supporting body tissue with same
US20070149690A1 (en) * 2005-12-23 2007-06-28 Boston Scientific Scimed, Inc. Functionalized block copolymers
US9956085B2 (en) 2005-12-23 2018-05-01 DePuy Synthes Products, Inc. Flexible elongated chain implant and method of supporting body tissue with same
US9125906B2 (en) 2005-12-28 2015-09-08 DePuy Synthes Products, Inc. Treatment of peripheral vascular disease using umbilical cord tissue-derived cells
US9585918B2 (en) 2005-12-28 2017-03-07 DePuy Synthes Products, Inc. Treatment of peripheral vascular disease using umbilical cord tissue-derived cells
US20080195112A1 (en) * 2006-01-23 2008-08-14 Liu Y King Vertebroplasty methods with optimized shear strength and crack propagation resistance
US20070185231A1 (en) * 2006-01-23 2007-08-09 Liu Y K Bone cement composite containing particles in a non-uniform spatial distribution and devices for implementation
WO2007087400A3 (en) * 2006-01-23 2008-03-06 Bond Therapeutics Llc V Bone cement composite containing particles in a non-uniform spatial distribution and devices for implementation
US20100160922A1 (en) * 2006-01-23 2010-06-24 Osseon Therapeutics, Inc. Two-part bone cement composite containing particles in a non-uniform spatial distribution and devices for implementation
US7824703B2 (en) 2006-02-01 2010-11-02 Warsaw Orthopedics, Inc. Medical implants with reservoir(s), and materials preparable from same
US9931435B2 (en) 2006-02-01 2018-04-03 Warsaw Orthopedic, Inc. Medical implants with reservoir(s), and materials preparable from same
US20100298815A1 (en) * 2006-02-01 2010-11-25 Warsaw Orthopedic, Inc. Medical implants with reservoir(s), and materials preparable from same
US9320708B2 (en) 2006-02-01 2016-04-26 Warsaw Orthopedic, Inc. Medical implants with reservoir(s)
US8697114B2 (en) 2006-02-01 2014-04-15 Jeffrey L. Scifert Medical implants with reservoir(s), and materials preparable from same
US20070190083A1 (en) * 2006-02-01 2007-08-16 Scifert Jeffrey L Medical implants with reservoir (s), and materials preparable from same
US8568765B2 (en) 2006-02-08 2013-10-29 Northwestern University Poly (diol co-citrate) hydroxyapatite composite for tissue engineering and orthapaedic fixation devices
WO2007092559A2 (en) * 2006-02-08 2007-08-16 Northwestern University A poly (diol-co-citrate) hydroxyapatite composite for tissue engineering and orthopaedic fixation devices
WO2007092559A3 (en) * 2006-02-08 2008-02-21 Univ Northwestern A poly (diol-co-citrate) hydroxyapatite composite for tissue engineering and orthopaedic fixation devices
US8992967B2 (en) 2006-02-08 2015-03-31 Northwestern University Poly (diol-co-citrate) hydroxyapatite composite for tissue engineering and orthopaedic fixation devices
US20070224245A1 (en) * 2006-02-08 2007-09-27 Northwestern University Poly (diol co-citrate) hydroxyapatite composite for tissue engineering and orthopaedic fixation devices
US20140343689A1 (en) * 2006-03-14 2014-11-20 Kci Licensing, Inc. System and method for percutaneously administering reduced pressure treatment using a flowable manifold
US20070270970A1 (en) * 2006-03-14 2007-11-22 Sdgi Holdings, Inc. Spinal implants with improved wear resistance
US20070270971A1 (en) * 2006-03-14 2007-11-22 Sdgi Holdings, Inc. Intervertebral prosthetic disc with improved wear resistance
US20070270953A1 (en) * 2006-03-29 2007-11-22 Sdgi Holdings, Inc. Transformable spinal implants and methods of use
US7993404B2 (en) 2006-03-29 2011-08-09 Warsaw Orthopedic, Inc. Transformable spinal implants and methods of use
WO2007114996A1 (en) * 2006-03-31 2007-10-11 Warsaw Orthopedic, Inc. Spinal implants with improved mechanical response
US20070233246A1 (en) * 2006-03-31 2007-10-04 Sdgi Holdings, Inc. Spinal implants with improved mechanical response
US8658197B2 (en) 2006-04-14 2014-02-25 Warsaw Orthopedic, Inc. Disruptable medical implants with reservoir (s), and materials preparable from same
US9254156B2 (en) 2006-04-26 2016-02-09 Illuminoss Medical, Inc. Apparatus for delivery of reinforcing materials to bone
US10456184B2 (en) 2006-04-26 2019-10-29 Illuminoss Medical, Inc. Apparatus for delivery of reinforcing materials to bone
US20080039854A1 (en) * 2006-04-26 2008-02-14 Illuminoss Medical, Inc. Apparatus and methods for delivery of reinforcing materials to bone
US7806900B2 (en) 2006-04-26 2010-10-05 Illuminoss Medical, Inc. Apparatus and methods for delivery of reinforcing materials to bone
US11331132B2 (en) 2006-04-26 2022-05-17 Illuminoss Medical, Inc. Apparatus for delivery of reinforcing materials to bone
US20100331850A1 (en) * 2006-04-26 2010-12-30 Illuminoss Medical, Inc. Apparatus for delivery of reinforcing materials to bone
US20120289968A1 (en) * 2006-04-26 2012-11-15 Illuminoss Medical, Inc. Apparatus for Delivery of Reinforcing Materials to Bone
US9265549B2 (en) * 2006-04-26 2016-02-23 Illuminoss Medical, Inc. Apparatus for delivery of reinforcing materials to bone
US8348956B2 (en) 2006-04-26 2013-01-08 Illuminoss Medical, Inc. Apparatus and methods for reinforcing bone
US9724147B2 (en) 2006-04-26 2017-08-08 Illuminoss Medical, Inc. Apparatus for delivery of reinforcing materials to bone
US8668701B2 (en) * 2006-04-26 2014-03-11 Illuminoss Medical, Inc. Apparatus for delivery of reinforcing materials to bone
US20140142581A1 (en) * 2006-04-26 2014-05-22 Illuminoss Medical, Inc. Apparatus for Delivery of Reinforcing Materials to Bone
US8246628B2 (en) * 2006-04-26 2012-08-21 Illuminoss Medical, Inc. Apparatus for delivery of reinforcing materials to bone
US20220142692A1 (en) * 2006-05-03 2022-05-12 P Tech, Llc Methods and Devices for Utilizing Bondable Materials
US20070260315A1 (en) * 2006-05-03 2007-11-08 Foley Kevin T Devices and methods for disc height restoration
US10898611B2 (en) 2006-05-08 2021-01-26 Nuvasive, Inc. Cancellous bone product including viable osteogenic cells
US20080262633A1 (en) * 2006-05-08 2008-10-23 Williams Michelle Leroux Cancellous bone treated with collagenase and essentially free of blood cells
US10507265B2 (en) 2006-05-08 2019-12-17 Nuvasive, Inc. Cancellous bone product including viable osteogenic cells
US11865227B2 (en) 2006-05-08 2024-01-09 Nuvasive, Inc. Cancellous bone product including viable osteogenic cells
US8226722B2 (en) * 2006-06-08 2012-07-24 Francis Pflum Sac for use in spinal surgery
US10143560B2 (en) 2006-06-08 2018-12-04 Francis Pflum Sac for use in spinal surgery
US20070299523A1 (en) * 2006-06-08 2007-12-27 Francis Pflum Sac for use in spinal surgery
US20080021556A1 (en) * 2006-07-21 2008-01-24 Edie Jason A Expandable vertebral implant and methods of use
US20080021557A1 (en) * 2006-07-24 2008-01-24 Warsaw Orthopedic, Inc. Spinal motion-preserving implants
US20080021462A1 (en) * 2006-07-24 2008-01-24 Warsaw Orthopedic Inc. Spinal stabilization implants
US20080058932A1 (en) * 2006-07-26 2008-03-06 Warsaw Orthopedic Inc. Rigidization-on-command orthopedic devices and methods
US9713538B2 (en) 2006-07-31 2017-07-25 DePuy Synthes Products, Inc. Spinal fusion implant
US9737413B2 (en) 2006-07-31 2017-08-22 DePuy Synthes Products, Inc. Spinal fusion implant
US9387091B2 (en) 2006-07-31 2016-07-12 DePuy Synthes Products, Inc. Spinal fusion implant
US10695191B2 (en) 2006-07-31 2020-06-30 DePuy Synthes Products, Inc. Spinal fusion implant
US10010428B2 (en) 2006-07-31 2018-07-03 DePuy Synthes Products, Inc. Spinal fusion implant
US9320614B2 (en) 2006-07-31 2016-04-26 DePuy Synthes Products, Inc. Spinal fusion implant
US9878133B2 (en) 2006-08-07 2018-01-30 W. L. Gore & Associates, Inc. Inflatable imbibed polymer devices
US20140088683A1 (en) * 2006-08-07 2014-03-27 W. L. Gore & Associates, Inc. Non-shortening wrapped balloon
US10881840B2 (en) 2006-08-07 2021-01-05 W. L. Gore & Associates, Inc. Inflatable imbibed polymer devices
WO2008018096A1 (en) * 2006-08-08 2008-02-14 Radames Binotto Intervertebral spacer with applicator device
US9526525B2 (en) 2006-08-22 2016-12-27 Neuropro Technologies, Inc. Percutaneous system for dynamic spinal stabilization
US20080249633A1 (en) * 2006-08-22 2008-10-09 Tim Wu Biodegradable Materials and Methods of Use
US9642932B2 (en) 2006-09-14 2017-05-09 DePuy Synthes Products, Inc. Bone cement and methods of use thereof
US10272174B2 (en) 2006-09-14 2019-04-30 DePuy Synthes Products, Inc. Bone cement and methods of use thereof
US8950929B2 (en) 2006-10-19 2015-02-10 DePuy Synthes Products, LLC Fluid delivery system
US10494158B2 (en) 2006-10-19 2019-12-03 DePuy Synthes Products, Inc. Fluid delivery system
US8088147B2 (en) 2006-10-24 2012-01-03 Trans1 Inc. Multi-membrane prosthetic nucleus
US20080262502A1 (en) * 2006-10-24 2008-10-23 Trans1, Inc. Multi-membrane prosthetic nucleus
US20100137991A1 (en) * 2006-10-24 2010-06-03 Trans1, Inc. Prosthetic nucleus with a preformed membrane
US8328846B2 (en) 2006-10-24 2012-12-11 Trans1 Inc. Prosthetic nucleus with a preformed membrane
US20100145462A1 (en) * 2006-10-24 2010-06-10 Trans1 Inc. Preformed membranes for use in intervertebral disc spaces
WO2008051254A1 (en) * 2006-10-27 2008-05-02 The Regents Of The University Of Colorado A polymer formulation a method of determining a polymer formulation and a method of determining a polymer fabrication
US20100041770A1 (en) * 2006-10-31 2010-02-18 Synthes Usa, Llc Polymer-ceramic composite and method
US20080109003A1 (en) * 2006-11-08 2008-05-08 Peckham Steven M Methods of employing calcium phosphate cement compositions and osteoinductive proteins to effect vertebrae interbody fusion absent an interbody device
US8388626B2 (en) * 2006-11-08 2013-03-05 Warsaw Orthopedic, Inc. Methods of employing calcium phosphate cement compositions and osteoinductive proteins to effect vertebrae interbody fusion absent an interbody device
US10543025B2 (en) 2006-11-10 2020-01-28 Illuminoss Medical, Inc. Systems and methods for internal bone fixation
US8366711B2 (en) 2006-11-10 2013-02-05 Illuminoss Medical, Inc. Systems and methods for internal bone fixation
US8906031B2 (en) 2006-11-10 2014-12-09 Illuminoss Medical, Inc. Systems and methods for internal bone fixation
US9717542B2 (en) 2006-11-10 2017-08-01 Illuminoss Medical, Inc. Systems and methods for internal bone fixation
US8906030B2 (en) 2006-11-10 2014-12-09 Illuminoss Medical, Inc. Systems and methods for internal bone fixation
US11259847B2 (en) * 2006-11-10 2022-03-01 Illuminoss Medical, Inc. Systems and methods for internal bone fixation
US7811284B2 (en) * 2006-11-10 2010-10-12 Illuminoss Medical, Inc. Systems and methods for internal bone fixation
US9433450B2 (en) 2006-11-10 2016-09-06 Illuminoss Medical, Inc. Systems and methods for internal bone fixation
US8734460B2 (en) 2006-11-10 2014-05-27 Illuminoss Medical, Inc. Systems and methods for internal bone fixation
US7879041B2 (en) 2006-11-10 2011-02-01 Illuminoss Medical, Inc. Systems and methods for internal bone fixation
US11793556B2 (en) 2006-11-10 2023-10-24 Illuminoss Medical, Inc. Systems and methods for internal bone fixation
US20080133012A1 (en) * 2006-11-16 2008-06-05 Mcguckin James F Spinal implant and method of use
US8920506B2 (en) 2006-11-16 2014-12-30 Rex Medical, L.P. Spinal implant and method of use
US9259324B2 (en) * 2006-11-16 2016-02-16 Rex Medical, L.P. Spinal implant and method of use
US8287599B2 (en) 2006-11-16 2012-10-16 Rex Medical, L.P. Spinal implant and method of use
US20150094817A1 (en) * 2006-11-16 2015-04-02 Rex Medical, L.P. Spinal implant and method of use
US8142507B2 (en) 2006-11-16 2012-03-27 Rex Medical, L.P. Spinal implant and method of use
US8114159B2 (en) * 2006-11-20 2012-02-14 Depuy Spine, Inc. Anterior spinal vessel protector
US20080119851A1 (en) * 2006-11-20 2008-05-22 Depuy Spine, Inc. Anterior spinal vessel protector
US8734517B2 (en) 2006-11-20 2014-05-27 DePuy Synthes Products, LLP Medical procedure involving protective pad
US11712345B2 (en) 2006-12-07 2023-08-01 DePuy Synthes Products, Inc. Intervertebral implant
US11432942B2 (en) 2006-12-07 2022-09-06 DePuy Synthes Products, Inc. Intervertebral implant
US10398566B2 (en) 2006-12-07 2019-09-03 DePuy Synthes Products, Inc. Intervertebral implant
US11497618B2 (en) 2006-12-07 2022-11-15 DePuy Synthes Products, Inc. Intervertebral implant
US11660206B2 (en) 2006-12-07 2023-05-30 DePuy Synthes Products, Inc. Intervertebral implant
US11642229B2 (en) 2006-12-07 2023-05-09 DePuy Synthes Products, Inc. Intervertebral implant
US10390963B2 (en) 2006-12-07 2019-08-27 DePuy Synthes Products, Inc. Intervertebral implant
US10583015B2 (en) 2006-12-07 2020-03-10 DePuy Synthes Products, Inc. Intervertebral implant
US11273050B2 (en) 2006-12-07 2022-03-15 DePuy Synthes Products, Inc. Intervertebral implant
US8979931B2 (en) * 2006-12-08 2015-03-17 DePuy Synthes Products, LLC Nucleus replacement device and method
US20080140201A1 (en) * 2006-12-08 2008-06-12 Shawn Stad Nucleus Replacement Device and Method
US11045324B2 (en) 2006-12-08 2021-06-29 DePuy Synthes Products, Inc. Method of implanting a curable implant material
US10610369B2 (en) 2006-12-08 2020-04-07 DePuy Synthes Products, Inc. Method of implanting a curable implant material
US8497121B2 (en) 2006-12-20 2013-07-30 Zimmer Orthobiologics, Inc. Method of obtaining viable small tissue particles and use for tissue repair
US20080154234A1 (en) * 2006-12-20 2008-06-26 Zimmer Orthobiologics, Inc. Apparatus and method for delivering a biocompatible material to a surgical site
US7720533B2 (en) 2006-12-20 2010-05-18 Zimmer Orthobiologicals, Inc. Apparatus and method for delivering a biocompatible material to a surgical site
US20100191281A1 (en) * 2006-12-20 2010-07-29 Essy Behravesh Apparatus and Method for Delivering a Biocompatible Material to a Surgical Site
US20080154373A1 (en) * 2006-12-21 2008-06-26 Warsaw Orthopedic, Inc. Curable orthopedic implant devices configured to be hardened after placement in vivo
US8663328B2 (en) 2006-12-21 2014-03-04 Warsaw Orthopedic, Inc. Methods for positioning a load-bearing component of an orthopedic implant device by inserting a malleable device that hardens in vivo
US7771476B2 (en) 2006-12-21 2010-08-10 Warsaw Orthopedic Inc. Curable orthopedic implant devices configured to harden after placement in vivo by application of a cure-initiating energy before insertion
US8480718B2 (en) * 2006-12-21 2013-07-09 Warsaw Orthopedic, Inc. Curable orthopedic implant devices configured to be hardened after placement in vivo
US20080154368A1 (en) * 2006-12-21 2008-06-26 Warsaw Orthopedic, Inc. Curable orthopedic implant devices configured to harden after placement in vivo by application of a cure-initiating energy before insertion
US11020237B2 (en) 2006-12-22 2021-06-01 Medos International Sarl Composite vertebral spacers and instrument
US20080167685A1 (en) * 2007-01-05 2008-07-10 Warsaw Orthopedic, Inc. System and Method For Percutanously Curing An Implantable Device
WO2008094217A1 (en) * 2007-01-31 2008-08-07 Ouroboros, Inc. Mechanical apparatus and method for artificial disc replacement
US10575963B2 (en) 2007-02-21 2020-03-03 Benvenue Medical, Inc. Devices for treating the spine
US8968408B2 (en) 2007-02-21 2015-03-03 Benvenue Medical, Inc. Devices for treating the spine
US9642712B2 (en) 2007-02-21 2017-05-09 Benvenue Medical, Inc. Methods for treating the spine
US10285821B2 (en) 2007-02-21 2019-05-14 Benvenue Medical, Inc. Devices for treating the spine
US10426629B2 (en) 2007-02-21 2019-10-01 Benvenue Medical, Inc. Devices for treating the spine
US20190216612A1 (en) * 2007-02-21 2019-07-18 Benvenue Medical, Inc. Devices For Treating The Spine
US9138318B2 (en) 2007-04-12 2015-09-22 Zimmer, Inc. Apparatus for forming an implant
US20100260723A1 (en) * 2007-05-02 2010-10-14 Aldemar Hegewald Implantable system for an intervertebral disc and intervertebral disc implant
US9402737B2 (en) 2007-06-26 2016-08-02 DePuy Synthes Products, Inc. Highly lordosed fusion cage
US8900307B2 (en) 2007-06-26 2014-12-02 DePuy Synthes Products, LLC Highly lordosed fusion cage
US9839530B2 (en) 2007-06-26 2017-12-12 DePuy Synthes Products, Inc. Highly lordosed fusion cage
US10973652B2 (en) 2007-06-26 2021-04-13 DePuy Synthes Products, Inc. Highly lordosed fusion cage
US11622868B2 (en) 2007-06-26 2023-04-11 DePuy Synthes Products, Inc. Highly lordosed fusion cage
US20090005870A1 (en) * 2007-06-26 2009-01-01 John Riley Hawkins Highly Lordosed Fusion Cage
US20100241229A1 (en) * 2007-07-03 2010-09-23 Synergy Biosurgical Ag Medical implant
US10278747B2 (en) 2007-07-03 2019-05-07 Medacta International S.A. Medical implant
US9398927B2 (en) 2007-07-03 2016-07-26 Synergy Biosurgical Ag Medical implant
US10765526B2 (en) 2007-07-07 2020-09-08 Jmea Corporation Disk fusion implant
US10039647B2 (en) 2007-07-07 2018-08-07 Jmea Corporation Disk fusion implant
US7922767B2 (en) 2007-07-07 2011-04-12 Jmea Corporation Disk fusion implant
US8518117B2 (en) * 2007-07-07 2013-08-27 Jmea Corporation Disc fusion implant
US8518118B2 (en) 2007-07-07 2013-08-27 Jmea Corporation Disc fusion implant
US20090012623A1 (en) * 2007-07-07 2009-01-08 Jmea Corporation Disk Fusion Implant
US8197548B2 (en) 2007-07-07 2012-06-12 Jmea Corporation Disk fusion implant
US8696753B2 (en) 2007-07-07 2014-04-15 Jmea Corporation Disk fusion implant
US20090012621A1 (en) * 2007-07-07 2009-01-08 James Sack A Disc Fusion Implant
US8728130B2 (en) 2007-07-16 2014-05-20 X-Spine Systems, Inc. Implant plate screw locking system and screw having a locking member
US7963982B2 (en) 2007-07-16 2011-06-21 X-Spine Systems, Inc. Implant plate screw locking system and screw having a locking member
US9044333B2 (en) 2007-07-27 2015-06-02 R Tree Innovations, Llc Inter-body implantation system and method
US10940013B2 (en) 2007-07-27 2021-03-09 R Tree Innovations, Llc Interbody implantation system and method
US20090069900A1 (en) * 2007-09-11 2009-03-12 Bezaleel, Llc. Method for forming a bioresorbable composite implant in a bone
US7959684B2 (en) * 2007-09-11 2011-06-14 Joy Medical Devices Corporation Method for forming a bioresorbable composite implant in a bone
US9457125B2 (en) 2007-09-17 2016-10-04 Synergy Biosurgical Ag Medical implant with electromagnetic radiation responsive polymer and related methods
US8777618B2 (en) 2007-09-17 2014-07-15 Synergy Biosurgical Ag Medical implant II
US20090088789A1 (en) * 2007-09-28 2009-04-02 O'neil Michael J Balloon With Shape Control For Spinal Procedures
US20160331362A1 (en) * 2007-09-28 2016-11-17 DePuy Synthes Products, Inc. Balloon With Shape Control For Spinal Procedures
US9421056B2 (en) * 2007-09-28 2016-08-23 DePuy Synthes Products, Inc. Balloon with shape control for spinal procedures
US9936938B2 (en) * 2007-09-28 2018-04-10 DePuy Synthes Products, Inc. Balloon with shape control for spinal procedures
US10786231B2 (en) 2007-09-28 2020-09-29 DePuy Synthes Products, Inc. Balloon with shape control for spinal procedures
US8043381B2 (en) * 2007-10-29 2011-10-25 Zimmer Spine, Inc. Minimally invasive interbody device and method
US20090112323A1 (en) * 2007-10-29 2009-04-30 Zimmer Spine, Inc. Minimally invasive interbody device and method
US20100324689A1 (en) * 2007-10-30 2010-12-23 Darren Donald Obrigkeit Implant comprising thermoplastic elastomer
US9427289B2 (en) 2007-10-31 2016-08-30 Illuminoss Medical, Inc. Light source
US8827981B2 (en) 2007-11-16 2014-09-09 Osseon Llc Steerable vertebroplasty system with cavity creation element
US7811291B2 (en) 2007-11-16 2010-10-12 Osseon Therapeutics, Inc. Closed vertebroplasty bone cement injection system
US9510885B2 (en) 2007-11-16 2016-12-06 Osseon Llc Steerable and curvable cavity creation system
US7842041B2 (en) 2007-11-16 2010-11-30 Osseon Therapeutics, Inc. Steerable vertebroplasty system
US20090163958A1 (en) * 2007-12-20 2009-06-25 Peter Tarcha Compositions, devices, systems, and methods for inhibiting an inflammatory response
US8403968B2 (en) 2007-12-26 2013-03-26 Illuminoss Medical, Inc. Apparatus and methods for repairing craniomaxillofacial bones using customized bone plates
US8672982B2 (en) 2007-12-26 2014-03-18 Illuminoss Medical, Inc. Apparatus and methods for repairing craniomaxillofacial bones using customized bone plates
US9005254B2 (en) 2007-12-26 2015-04-14 Illuminoss Medical, Inc. Methods for repairing craniomaxillofacial bones using customized bone plate
US20090169597A1 (en) * 2007-12-27 2009-07-02 Ethicon, Incorporated Treatment of intervertebral disc degeneration using human umbilical cord tissue-derived cells
US20110280838A1 (en) * 2007-12-27 2011-11-17 Advanced Technologies And Regenerative Medicine, Llc Treatment of intervertebral disc degeneration using human umbilical cord tissue-derived cells
US10433977B2 (en) 2008-01-17 2019-10-08 DePuy Synthes Products, Inc. Expandable intervertebral implant and associated method of manufacturing the same
US11737881B2 (en) 2008-01-17 2023-08-29 DePuy Synthes Products, Inc. Expandable intervertebral implant and associated method of manufacturing the same
US9433510B2 (en) 2008-01-17 2016-09-06 DePuy Synthes Products, Inc. Expandable intervertebral implant and associated method of manufacturing the same
US9295562B2 (en) 2008-01-17 2016-03-29 DePuy Synthes Products, Inc. Expandable intervertebral implant and associated method of manufacturing the same
US10449058B2 (en) 2008-01-17 2019-10-22 DePuy Synthes Products, Inc. Expandable intervertebral implant and associated method of manufacturing the same
US20090246244A1 (en) * 2008-03-27 2009-10-01 Warsaw Orthopedic, Inc. Malleable multi-component implants and materials therefor
US8840913B2 (en) 2008-03-27 2014-09-23 Warsaw Orthopedic, Inc. Malleable multi-component implants and materials therefor
US9730982B2 (en) 2008-03-27 2017-08-15 Warsaw Orthopedic, Inc. Malleable multi-component implants and materials therefor
US11602438B2 (en) 2008-04-05 2023-03-14 DePuy Synthes Products, Inc. Expandable intervertebral implant
US11617655B2 (en) 2008-04-05 2023-04-04 DePuy Synthes Products, Inc. Expandable intervertebral implant
US9931223B2 (en) 2008-04-05 2018-04-03 DePuy Synthes Products, Inc. Expandable intervertebral implant
US9993350B2 (en) 2008-04-05 2018-06-12 DePuy Synthes Products, Inc. Expandable intervertebral implant
US9474623B2 (en) 2008-04-05 2016-10-25 DePuy Synthes Products, Inc. Expandable intervertebral implant
US9545314B2 (en) 2008-04-05 2017-01-17 DePuy Synthes Products, Inc. Expandable intervertebral implant
US9526625B2 (en) 2008-04-05 2016-12-27 DePuy Synthes Products, Inc. Expandable intervertebral implant
US11701234B2 (en) 2008-04-05 2023-07-18 DePuy Synthes Products, Inc. Expandable intervertebral implant
US11707359B2 (en) 2008-04-05 2023-07-25 DePuy Synthes Products, Inc. Expandable intervertebral implant
US11712342B2 (en) 2008-04-05 2023-08-01 DePuy Synthes Products, Inc. Expandable intervertebral implant
US9597195B2 (en) 2008-04-05 2017-03-21 DePuy Synthes Products, Inc. Expandable intervertebral implant
US11712341B2 (en) 2008-04-05 2023-08-01 DePuy Synthes Products, Inc. Expandable intervertebral implant
US9414934B2 (en) 2008-04-05 2016-08-16 DePuy Synthes Products, Inc. Expandable intervertebral implant
US10449056B2 (en) 2008-04-05 2019-10-22 DePuy Synthes Products, Inc. Expandable intervertebral implant
US20090270987A1 (en) * 2008-04-24 2009-10-29 Warsaw Orthopedic, Inc. Expandable vertebral implants and methods of use
US9421113B2 (en) 2008-04-24 2016-08-23 Henry F. Fabian Spine surgery method and inserter
US8062368B2 (en) 2008-04-24 2011-11-22 Warsaw Orthopedic, Inc. Expandable vertebral implants and methods of use
US8579977B2 (en) 2008-04-24 2013-11-12 Henry F. Fabian Spine surgery method and inserter
US9132208B2 (en) 2008-08-07 2015-09-15 Lifenet Health Composition for a tissue repair implant and methods of making the same
US20100036503A1 (en) * 2008-08-07 2010-02-11 Chen Silvia S Composition for a Tissue Repair Implant and Methods of Making the Same
US20100145454A1 (en) * 2008-12-09 2010-06-10 Zimmer Spine, Inc. Intervertebral disc nucleus replacement prosthesis
US8545895B2 (en) 2009-01-08 2013-10-01 The University Court Of The University Of Aberdeen Silicate-substituted hydroxyapatite
US20100173009A1 (en) * 2009-01-08 2010-07-08 Iain Ronald Gibson Silicate-substituted hydroxyapatite
US20120046750A1 (en) * 2009-03-05 2012-02-23 Dsm Ip Assets B.V. Spinal fusion cage
US9452061B2 (en) * 2009-03-05 2016-09-27 Dsm Ip Assets B.V. Spinal fusion cage
US8535327B2 (en) 2009-03-17 2013-09-17 Benvenue Medical, Inc. Delivery apparatus for use with implantable medical devices
WO2010109460A1 (en) * 2009-03-23 2010-09-30 Chi 2 Gel Ltd. Restorative device for intervertebral discs
US9526620B2 (en) 2009-03-30 2016-12-27 DePuy Synthes Products, Inc. Zero profile spinal fusion cage
US11612491B2 (en) 2009-03-30 2023-03-28 DePuy Synthes Products, Inc. Zero profile spinal fusion cage
US10624758B2 (en) 2009-03-30 2020-04-21 DePuy Synthes Products, Inc. Zero profile spinal fusion cage
US9592129B2 (en) 2009-03-30 2017-03-14 DePuy Synthes Products, Inc. Zero profile spinal fusion cage
US20110087231A1 (en) * 2009-04-03 2011-04-14 Light Cure, Llc Devices and Injectable or Implantable Compositions for Intervertebral Fusion
US8328402B2 (en) 2009-04-06 2012-12-11 Illuminoss Medical, Inc. Attachment system for light-conducting fibers
US8936382B2 (en) 2009-04-06 2015-01-20 Illuminoss Medical, Inc. Attachment system for light-conducting fibers
US8210729B2 (en) 2009-04-06 2012-07-03 Illuminoss Medical, Inc. Attachment system for light-conducting fibers
US20100256766A1 (en) * 2009-04-07 2010-10-07 Hibri Nadi S Percutaneous Implantable Nuclear Prosthesis
US10028839B2 (en) 2009-04-07 2018-07-24 Spinal Stabilization Technologies, Llc Percutaneous implantable nuclear prosthesis
US8574233B2 (en) 2009-04-07 2013-11-05 Illuminoss Medical, Inc. Photodynamic bone stabilization systems and methods for reinforcing bone
US8636803B2 (en) 2009-04-07 2014-01-28 Spinal Stabilization Technologies, Llc Percutaneous implantable nuclear prosthesis
US9592130B2 (en) 2009-04-07 2017-03-14 Spinal Stabilization Technologies, Llc Percutaneous implantable nuclear prosthesis
US8512338B2 (en) 2009-04-07 2013-08-20 Illuminoss Medical, Inc. Photodynamic bone stabilization systems and methods for reinforcing bone
US20100268155A1 (en) * 2009-04-20 2010-10-21 Warsaw Orthopedic, Inc. Method For Stabilizing An Intervertebral Disc Device
US8377136B2 (en) * 2009-04-20 2013-02-19 Warsaw Orthopedic, Inc. Method for stabilizing an intervertebral disc device
US11197681B2 (en) 2009-05-20 2021-12-14 Merit Medical Systems, Inc. Steerable curvable vertebroplasty drill
US9750552B2 (en) 2009-07-06 2017-09-05 DePuy Synthes Products, Inc. Expandable fixation assemblies
US9814599B2 (en) 2009-07-09 2017-11-14 R Tree Innovations, Llc Inter-body implantation system and method
US8828082B2 (en) 2009-07-09 2014-09-09 R Tree Innovations, Llc Inter-body implant
US10806594B2 (en) 2009-07-09 2020-10-20 R Tree Innovations, Llc Inter-body implant
US9877844B2 (en) 2009-07-09 2018-01-30 R Tree Innovations, Llc Inter-body implant
US10835386B2 (en) 2009-07-09 2020-11-17 R Tree Innovations, Llc Inter-body implantation system and method
US8911503B2 (en) * 2009-07-10 2014-12-16 Peter Forsell Hip joint device, system and method
US20120109329A1 (en) * 2009-07-10 2012-05-03 Milux Holding Sa Hip joint device, system and method
US9125706B2 (en) 2009-08-19 2015-09-08 Illuminoss Medical, Inc. Devices and methods for bone alignment, stabilization and distraction
US8870965B2 (en) 2009-08-19 2014-10-28 Illuminoss Medical, Inc. Devices and methods for bone alignment, stabilization and distraction
US8915966B2 (en) 2009-08-19 2014-12-23 Illuminoss Medical, Inc. Devices and methods for bone alignment, stabilization and distraction
US20110066244A1 (en) * 2009-09-11 2011-03-17 William Frasier Minimally Invasive Intervertebral Staple Distraction Devices
US8685097B2 (en) 2009-09-11 2014-04-01 DePuy Sunthes Products, LLC. Minimally invasive intervertebral staple distraction devices
US9216093B2 (en) 2009-09-11 2015-12-22 DePuy Synthes Products, Inc. Minimally invasive intervertebral staple distraction devices
US9744054B2 (en) 2009-09-11 2017-08-29 DePuy Synthes Products, Inc. Minimally invasive intervertebral staple distraction devices
US8403988B2 (en) 2009-09-11 2013-03-26 Depuy Spine, Inc. Minimally invasive intervertebral staple distraction devices
US9615933B2 (en) 2009-09-15 2017-04-11 DePuy Synthes Products, Inc. Expandable ring intervertebral fusion device
US20110066192A1 (en) * 2009-09-15 2011-03-17 William Frasier Expandable Ring Intervertebral Fusion Device
US10888361B2 (en) 2009-09-21 2021-01-12 REVA Medical LLC Devices, compositions and methods for bone and tissue augmentation
US8702716B1 (en) 2009-09-21 2014-04-22 Reva Medical Inc. Devices, compositions and methods for bone and tissue augmentation
US9180017B2 (en) * 2009-10-13 2015-11-10 Nicholas Poulos Lumbar implant
US20130178939A1 (en) * 2009-10-13 2013-07-11 Nicholas Poulos Expandable interbody implant and method
US9211195B2 (en) 2009-10-13 2015-12-15 Nicholas Poulos Expandable interbody implant and method
US8906099B2 (en) * 2009-10-13 2014-12-09 Nicholas Poulos Expandable interbody implant and method
US20110087329A1 (en) * 2009-10-13 2011-04-14 Nicholas Poulos Lumbar implant
US20160302926A1 (en) * 2009-11-30 2016-10-20 DePuy Synthes Products, Inc. Expandable Implant
US9402725B2 (en) 2009-11-30 2016-08-02 DePuy Synthes Products, Inc. Expandable implant
US8608743B2 (en) * 2009-11-30 2013-12-17 DePuy Synthes Products, LLC Expandable implant
US20110160870A1 (en) * 2009-11-30 2011-06-30 Adrian Baumgartner Expandable implant
US10022228B2 (en) * 2009-11-30 2018-07-17 DePuy Synthes Products, Inc. Expandable implant
US20120016369A1 (en) * 2009-12-07 2012-01-19 O'halloran Damien Methods and Apparatus For Treating Vertebral Fractures
WO2011071851A1 (en) * 2009-12-07 2011-06-16 Globus Medical, Inc. Methods and apparatus for treating vertebral fractures
US8734458B2 (en) 2009-12-07 2014-05-27 Globus Medical, Inc. Methods and apparatus for treating vertebral fractures
US20120010624A1 (en) * 2009-12-07 2012-01-12 O'halloran Damien Methods and Apparatus For Treating Vertebral Fractures
US10543107B2 (en) 2009-12-07 2020-01-28 Samy Abdou Devices and methods for minimally invasive spinal stabilization and instrumentation
US20180235776A1 (en) * 2009-12-07 2018-08-23 Samy Abdou Devices and methods for minimally invasive spinal stablization and instrumentation
US10405906B2 (en) 2009-12-07 2019-09-10 Globus Medical, Inc. Methods and apparatus for treating vertebral fractures
US10610380B2 (en) 2009-12-07 2020-04-07 Samy Abdou Devices and methods for minimally invasive spinal stabilization and instrumentation
US11090092B2 (en) 2009-12-07 2021-08-17 Globus Medical Inc. Methods and apparatus for treating vertebral fractures
US9526538B2 (en) * 2009-12-07 2016-12-27 Globus Medical, Inc. Methods and apparatus for treating vertebral fractures
US10285741B2 (en) 2009-12-07 2019-05-14 Globus Medical, Inc. Methods and apparatus for treating vertebral fractures
US9326799B2 (en) 2009-12-07 2016-05-03 Globus Medical, Inc. Methods and apparatus for treating vertebral fractures
US20110137317A1 (en) * 2009-12-07 2011-06-09 O'halloran Damien Methods and Apparatus For Treating Vertebral Fractures
US10945861B2 (en) 2009-12-07 2021-03-16 Samy Abdou Devices and methods for minimally invasive spinal stabilization and instrumentation
US10857004B2 (en) * 2009-12-07 2020-12-08 Samy Abdou Devices and methods for minimally invasive spinal stabilization and instrumentation
US9801725B2 (en) 2009-12-09 2017-10-31 DePuy Synthes Products, Inc. Aspirating implants and method of bony regeneration
US10342662B2 (en) 2009-12-09 2019-07-09 DePuy Synthes Products, Inc. Aspirating implants and method of bony regeneration
US9393129B2 (en) 2009-12-10 2016-07-19 DePuy Synthes Products, Inc. Bellows-like expandable interbody fusion cage
US11607321B2 (en) 2009-12-10 2023-03-21 DePuy Synthes Products, Inc. Bellows-like expandable interbody fusion cage
US10500062B2 (en) 2009-12-10 2019-12-10 DePuy Synthes Products, Inc. Bellows-like expandable interbody fusion cage
US20110144753A1 (en) * 2009-12-10 2011-06-16 Connie Marchek Bellows-Like Expandable Interbody Fusion Cage
US9730946B2 (en) 2010-01-15 2017-08-15 Rutgers, The State University Of New Jersey Use of vanadium compounds to accelerate bone healing
US8936804B2 (en) 2010-01-15 2015-01-20 Rutgers, The State University Of New Jersey Use of vanadium compounds to accelerate bone healing
US20110202062A1 (en) * 2010-02-18 2011-08-18 O'halloran Damien Methods and Apparatus For Treating Vertebral Fractures
US9220554B2 (en) * 2010-02-18 2015-12-29 Globus Medical, Inc. Methods and apparatus for treating vertebral fractures
US20110202064A1 (en) * 2010-02-18 2011-08-18 O'halloran Damien Methods and Apparatus For Treating Vertebral Fractures
US9295509B2 (en) 2010-02-18 2016-03-29 Globus Medical, Inc. Methods and apparatus for treating vertebral fractures
US20110238072A1 (en) * 2010-03-26 2011-09-29 Tyndall Dwight S Minimally Invasive Surgical (MIS) Technique and System for Performing an Interbody Lumbar Fusion with a Navigatable Intervertebral Disc Removal Device and Collapsible Intervertebral Device
US10624652B2 (en) 2010-04-29 2020-04-21 Dfine, Inc. System for use in treatment of vertebral fractures
US10130736B1 (en) 2010-05-14 2018-11-20 Musculoskeletal Transplant Foundation Tissue-derived tissuegenic implants, and methods of fabricating and using same
US11305035B2 (en) 2010-05-14 2022-04-19 Musculoskeletal Transplant Foundatiaon Tissue-derived tissuegenic implants, and methods of fabricating and using same
US20120130489A1 (en) * 2010-05-19 2012-05-24 Chernomorsky Ary S Methods and apparatus for in situ formation of surgical implants
US20130226296A1 (en) * 2010-05-19 2013-08-29 Transmed7, Llc Methods and apparatus for in situ formation of surgical implants
US8684965B2 (en) 2010-06-21 2014-04-01 Illuminoss Medical, Inc. Photodynamic bone stabilization and drug delivery systems
US10966840B2 (en) 2010-06-24 2021-04-06 DePuy Synthes Products, Inc. Enhanced cage insertion assembly
US11872139B2 (en) 2010-06-24 2024-01-16 DePuy Synthes Products, Inc. Enhanced cage insertion assembly
US10327911B2 (en) 2010-06-24 2019-06-25 DePuy Synthes Products, Inc. Enhanced cage insertion assembly
US9833334B2 (en) 2010-06-24 2017-12-05 DePuy Synthes Products, Inc. Enhanced cage insertion assembly
US9895236B2 (en) 2010-06-24 2018-02-20 DePuy Synthes Products, Inc. Enhanced cage insertion assembly
US11911287B2 (en) 2010-06-24 2024-02-27 DePuy Synthes Products, Inc. Lateral spondylolisthesis reduction cage
US9320615B2 (en) 2010-06-29 2016-04-26 DePuy Synthes Products, Inc. Distractible intervertebral implant
US10548741B2 (en) 2010-06-29 2020-02-04 DePuy Synthes Products, Inc. Distractible intervertebral implant
US11654033B2 (en) 2010-06-29 2023-05-23 DePuy Synthes Products, Inc. Distractible intervertebral implant
US9579215B2 (en) 2010-06-29 2017-02-28 DePuy Synthes Products, Inc. Distractible intervertebral implant
US9265616B2 (en) 2010-08-10 2016-02-23 DePuy Synthes Products, Inc. Expandable implant
US10369015B2 (en) 2010-09-23 2019-08-06 DePuy Synthes Products, Inc. Implant inserter having a laterally-extending dovetail engagement feature
US11678996B2 (en) 2010-09-23 2023-06-20 DePuy Synthes Products, Inc. Stand alone intervertebral fusion device
US11382768B2 (en) 2010-09-23 2022-07-12 DePuy Synthes Products, Inc. Implant inserter having a laterally-extending dovetail engagement feature
US11529241B2 (en) 2010-09-23 2022-12-20 DePuy Synthes Products, Inc. Fusion cage with in-line single piece fixation
US10492897B2 (en) * 2010-10-06 2019-12-03 Boston Scientific Scimed, Inc. Implants with absorbable and non-absorbable features for the treatment of female pelvic conditions
US20170035542A1 (en) * 2010-10-06 2017-02-09 Astora Women's Health, Llc Implants with absorbalble and non-absorbable features for the treatment of female pelvic conditions
US11452607B2 (en) 2010-10-11 2022-09-27 DePuy Synthes Products, Inc. Expandable interspinous process spacer implant
US10525169B2 (en) 2010-10-20 2020-01-07 206 Ortho, Inc. Method and apparatus for treating bone fractures, and/or for fortifying and/or augmenting bone, including the provision and use of composite implants, and novel composite structures which may be used for medical and non-medical applications
US11351261B2 (en) 2010-10-20 2022-06-07 206 Ortho, Inc. Method and apparatus for treating bone fractures, and/or for fortifying and/or augmenting bone, including the provision and use of composite implants
US11291483B2 (en) 2010-10-20 2022-04-05 206 Ortho, Inc. Method and apparatus for treating bone fractures, and/or for fortifying and/or augmenting bone, including the provision and use of composite implants
US10525168B2 (en) 2010-10-20 2020-01-07 206 Ortho, Inc. Method and apparatus for treating bone fractures, and/or for fortifying and/or augmenting bone, including the provision and use of composite implants, and novel composite structures which may be used for medical and non-medical applications
US11850323B2 (en) 2010-10-20 2023-12-26 206 Ortho, Inc. Implantable polymer for bone and vascular lesions
US11207109B2 (en) 2010-10-20 2021-12-28 206 Ortho, Inc. Method and apparatus for treating bone fractures, and/or for fortifying and/or augmenting bone, including the provision and use of composite implants, and novel composite structures which may be used for medical and non-medical applications
US10028776B2 (en) 2010-10-20 2018-07-24 206 Ortho, Inc. Method and apparatus for treating bone fractures, and/or for fortifying and/or augmenting bone, including the provision and use of composite implants
US11058796B2 (en) 2010-10-20 2021-07-13 206 Ortho, Inc. Method and apparatus for treating bone fractures, and/or for fortifying and/or augmenting bone, including the provision and use of composite implants, and novel composite structures which may be used for medical and non-medical applications
US10857261B2 (en) 2010-10-20 2020-12-08 206 Ortho, Inc. Implantable polymer for bone and vascular lesions
US11484627B2 (en) 2010-10-20 2022-11-01 206 Ortho, Inc. Method and apparatus for treating bone fractures, and/or for fortifying and/or augmenting bone, including the provision and use of composite implants, and novel composite structures which may be used for medical and non-medical applications
US10517654B2 (en) 2010-10-20 2019-12-31 206 Ortho, Inc. Method and apparatus for treating bone fractures, and/or for fortifying and/or augmenting bone, including the provision and use of composite implants
US9265794B2 (en) 2010-12-10 2016-02-23 Rutgers, The State University Of New Jersey Insulin-mimetics as therapeutic adjuncts for bone regeneration
US9144633B2 (en) 2010-12-10 2015-09-29 Rutgers, The State University Of New Jersey Implantable devices coated with insulin-mimetic vanadium compounds and methods thereof
US9999636B2 (en) 2010-12-10 2018-06-19 Rutgers, The State University Of New Jersey Insulin-mimetics as therapeutic adjuncts for bone regeneration
US10111689B2 (en) 2010-12-22 2018-10-30 Illuminoss Medical, Inc. Systems and methods for treating conditions and diseases of the spine
WO2012088432A1 (en) * 2010-12-22 2012-06-28 Illuminoss Medical, Inc. Systems and methods for treating conditions and diseases of the spine
US9179959B2 (en) 2010-12-22 2015-11-10 Illuminoss Medical, Inc. Systems and methods for treating conditions and diseases of the spine
US9855080B2 (en) 2010-12-22 2018-01-02 Illuminoss Medical, Inc. Systems and methods for treating conditions and diseases of the spine
US10772664B2 (en) 2010-12-22 2020-09-15 Illuminoss Medical, Inc. Systems and methods for treating conditions and diseases of the spine
AU2012255270B2 (en) * 2011-05-19 2017-03-23 DePuy Synthes Products, Inc. Treatment of intervertebral disc degeneration using human umbilical cord tissue-derived cells
US9314252B2 (en) 2011-06-24 2016-04-19 Benvenue Medical, Inc. Devices and methods for treating bone tissue
US8814873B2 (en) 2011-06-24 2014-08-26 Benvenue Medical, Inc. Devices and methods for treating bone tissue
US9931348B2 (en) 2011-07-06 2018-04-03 Rutgers, The State University Of New Jersey Vanadium compounds as therapeutic adjuncts for cartilage injury and repair
US9775661B2 (en) 2011-07-19 2017-10-03 Illuminoss Medical, Inc. Devices and methods for bone restructure and stabilization
US9144442B2 (en) 2011-07-19 2015-09-29 Illuminoss Medical, Inc. Photodynamic articular joint implants and methods of use
US11559343B2 (en) 2011-07-19 2023-01-24 Illuminoss Medical, Inc. Photodynamic articular joint implants and methods of use
US8936644B2 (en) 2011-07-19 2015-01-20 Illuminoss Medical, Inc. Systems and methods for joint stabilization
US9254195B2 (en) 2011-07-19 2016-02-09 Illuminoss Medical, Inc. Systems and methods for joint stabilization
US9855145B2 (en) 2011-07-19 2018-01-02 IlluminsOss Medical, Inc. Systems and methods for joint stabilization
US11141207B2 (en) 2011-07-19 2021-10-12 Illuminoss Medical, Inc. Photodynamic articular joint implants and methods of use
US10292823B2 (en) 2011-07-19 2019-05-21 Illuminoss Medical, Inc. Photodynamic articular joint implants and methods of use
US11452616B2 (en) 2011-08-09 2022-09-27 Neuropro Spinal Jaxx, Inc. Bone fusion device, apparatus and method
US10420654B2 (en) 2011-08-09 2019-09-24 Neuropro Technologies, Inc. Bone fusion device, system and method
US9358123B2 (en) 2011-08-09 2016-06-07 Neuropro Spinal Jaxx, Inc. Bone fusion device, apparatus and method
US11432940B2 (en) 2011-08-09 2022-09-06 Neuropro Technologies, Inc. Bone fusion device, system and method
US10736754B2 (en) 2011-08-09 2020-08-11 Neuropro Spinal Jaxx, Inc. Bone fusion device, apparatus and method
US10092422B2 (en) 2011-08-09 2018-10-09 Neuropro Spinal Jaxx, Inc. Bone fusion device, apparatus and method
US10292830B2 (en) 2011-08-09 2019-05-21 Neuropro Technologies, Inc. Bone fusion device, system and method
US10159582B2 (en) 2011-09-16 2018-12-25 DePuy Synthes Products, Inc. Removable, bone-securing cover plate for intervertebral fusion cage
US10813773B2 (en) 2011-09-16 2020-10-27 DePuy Synthes Products, Inc. Removable, bone-securing cover plate for intervertebral fusion cage
US11324608B2 (en) 2011-09-23 2022-05-10 Samy Abdou Spinal fixation devices and methods of use
US11517449B2 (en) 2011-09-23 2022-12-06 Samy Abdou Spinal fixation devices and methods of use
US10575961B1 (en) 2011-09-23 2020-03-03 Samy Abdou Spinal fixation devices and methods of use
US20140303730A1 (en) * 2011-11-30 2014-10-09 Beth Israel Deaconess Medical Center Systems and methods for endoscopic vertebral fusion
US9060870B2 (en) 2012-02-05 2015-06-23 Michael J. Milella, Jr. In-situ formed spinal implant
US9681962B2 (en) 2012-02-05 2017-06-20 Michael J. Milella, Jr. In-situ formed spinal implant
US20130218278A1 (en) * 2012-02-21 2013-08-22 Steve Wolfe Device and method for performing spinal interbody fusion
US11006982B2 (en) 2012-02-22 2021-05-18 Samy Abdou Spinous process fixation devices and methods of use
US11839413B2 (en) 2012-02-22 2023-12-12 Samy Abdou Spinous process fixation devices and methods of use
US11844702B2 (en) 2012-03-06 2023-12-19 DePuy Synthes Products, Inc. Nubbed plate
US20130282121A1 (en) * 2012-03-22 2013-10-24 Ann Prewett Spinal facet augmentation implant and method
US9532883B2 (en) 2012-04-13 2017-01-03 Neuropro Technologies, Inc. Bone fusion device
US11439517B2 (en) 2012-04-13 2022-09-13 Neuropro Technologies, Inc. Bone fusion device
US10709574B2 (en) 2012-04-13 2020-07-14 Neuropro Technologies, Inc. Bone fusion device
US10159583B2 (en) 2012-04-13 2018-12-25 Neuropro Technologies, Inc. Bone fusion device
US10016283B2 (en) 2012-04-13 2018-07-10 Neuropro Technologies, Inc. Bone fusion device
US20130297023A1 (en) * 2012-05-07 2013-11-07 Hee-Jeong Im Sampen Methods and Devices For Treating Intervertebral Disc Disease
US8939977B2 (en) 2012-07-10 2015-01-27 Illuminoss Medical, Inc. Systems and methods for separating bone fixation devices from introducer
US9585764B2 (en) * 2012-07-26 2017-03-07 Warsaw Orthopedic, Inc. Bone implant device
US10058433B2 (en) 2012-07-26 2018-08-28 DePuy Synthes Products, Inc. Expandable implant
US9561117B2 (en) 2012-07-26 2017-02-07 DePuy Synthes Products, Inc. Expandable implant
US9532881B2 (en) 2012-08-12 2017-01-03 Brian Albert Hauck Memory material implant system and methods of use
US10695105B2 (en) 2012-08-28 2020-06-30 Samy Abdou Spinal fixation devices and methods of use
US11559336B2 (en) 2012-08-28 2023-01-24 Samy Abdou Spinal fixation devices and methods of use
US9636235B2 (en) 2012-09-13 2017-05-02 H & M Innovations, Llc Bone infusion apparatus and methods for interbody grafts
US11173040B2 (en) 2012-10-22 2021-11-16 Cogent Spine, LLC Devices and methods for spinal stabilization and instrumentation
WO2014066808A1 (en) * 2012-10-25 2014-05-01 Rutgers, The State University Of New Jersey Insulin-mimetic local therapeutic adjuncts for enhancing spinal fusion
US10780197B1 (en) * 2012-10-29 2020-09-22 Nuvasive, Inc. Malleable, cryopreserved osteogenic compositions with viable cells
US11633522B1 (en) 2012-10-29 2023-04-25 Nuvasive, Inc. Malleable, cryopreserved osteogenic compositions with viable cells
US9358058B2 (en) 2012-11-05 2016-06-07 Globus Medical, Inc. Methods and apparatus for treating vertebral fractures
US11497616B2 (en) 2012-11-09 2022-11-15 DePuy Synthes Products, Inc. Interbody device with opening to allow packing graft and other biologics
US9687281B2 (en) 2012-12-20 2017-06-27 Illuminoss Medical, Inc. Distal tip for bone fixation devices
US10575882B2 (en) 2012-12-20 2020-03-03 Illuminoss Medical, Inc. Distal tip for bone fixation devices
US10167447B2 (en) 2012-12-21 2019-01-01 Zimmer, Inc. Supports and methods for promoting integration of cartilage tissue explants
US9717601B2 (en) 2013-02-28 2017-08-01 DePuy Synthes Products, Inc. Expandable intervertebral implant, system, kit and method
US11497619B2 (en) 2013-03-07 2022-11-15 DePuy Synthes Products, Inc. Intervertebral implant
US11850164B2 (en) 2013-03-07 2023-12-26 DePuy Synthes Products, Inc. Intervertebral implant
US10231843B2 (en) 2013-03-14 2019-03-19 Benvenue Medical, Inc. Spinal fusion implants and devices and methods for deploying such implants
US20160250032A1 (en) * 2013-03-14 2016-09-01 DePuy Synthes Products, Inc. Expandable coil spinal implant
WO2014140916A3 (en) * 2013-03-14 2015-01-08 Ranier Limited Intervertebral fusion implant cage
US20140277464A1 (en) * 2013-03-14 2014-09-18 Synthes Usa, Llc Expandable coil spinal implant
US20180116813A1 (en) * 2013-03-14 2018-05-03 DePuy Synthes Products, Inc. Expandable coil spinal implant
US9545321B2 (en) 2013-03-14 2017-01-17 Spinal Stabilization Technologies Llc Prosthetic spinal disk nucleus
US10828170B2 (en) 2013-03-14 2020-11-10 DePuy Synthes Products, Inc. Angulated rings and bonded foils for use with balloons for fusion and dynamic stabilization
US9889015B2 (en) * 2013-03-14 2018-02-13 DePuy Synthes Products, Inc. Expandable coil spinal implant
US9295479B2 (en) 2013-03-14 2016-03-29 Spinal Stabilization Technologies, Llc Surgical device
US9480574B2 (en) 2013-03-14 2016-11-01 Benvenue Medical, Inc. Spinal fusion implants and devices and methods for deploying such implants
US9572676B2 (en) 2013-03-14 2017-02-21 DePuy Synthes Products, Inc. Adjustable multi-volume balloon for spinal interventions
US11589999B2 (en) 2013-03-14 2023-02-28 DePuy Synthes Products, Inc. Angulated rings and bonded foils for use with balloons for fusion and dynamic stabilization
US11406513B2 (en) 2013-03-14 2022-08-09 Spinal Stabilization Technologies, Llc Prosthetic spinal disk nucleus
US10143561B2 (en) 2013-03-14 2018-12-04 DePuy Synthes Products, Inc. Angulated rings and bonded foils for use with balloons for fusion and dynamic stabilization
US10864085B2 (en) * 2013-03-14 2020-12-15 DePuy Synthes Products, Inc. Expandable coil spinal implant
US10085783B2 (en) 2013-03-14 2018-10-02 Izi Medical Products, Llc Devices and methods for treating bone tissue
EP2967897B1 (en) * 2013-03-14 2017-11-22 Depuy Synthes Products, Inc. Expandable coil spinal implant
US9358120B2 (en) * 2013-03-14 2016-06-07 DePuy Synthes Products, Inc. Expandable coil spinal implant
US9585761B2 (en) 2013-03-14 2017-03-07 DePuy Synthes Products, Inc. Angulated rings and bonded foils for use with balloons for fusion and dynamic stabilization
US11399956B2 (en) 2013-03-15 2022-08-02 Neuropro Technologies, Inc. Bodiless bone fusion device, apparatus and method
US10098757B2 (en) 2013-03-15 2018-10-16 Neuropro Technologies Inc. Bodiless bone fusion device, apparatus and method
US10575966B2 (en) 2013-03-15 2020-03-03 Neuropro Technologies, Inc. Bodiless bone fusion device, apparatus and method
US10179834B2 (en) 2013-04-10 2019-01-15 The University Of Melbourne Biodegradable network polymers for regenerative medicine and tissue engineering
WO2014190289A3 (en) * 2013-05-23 2015-02-26 206 Ortho, Inc. Method and apparatus for treating bone fractures, and/or for fortifying and/or augmenting bone, including the provision and use of composite implants
US10010609B2 (en) 2013-05-23 2018-07-03 206 Ortho, Inc. Method and apparatus for treating bone fractures, and/or for fortifying and/or augmenting bone, including the provision and use of composite implants
US20160128834A1 (en) * 2013-06-19 2016-05-12 Meir Yakir Scaffold implant system
WO2014209725A2 (en) 2013-06-24 2014-12-31 DePuy Synthes Products, LLC Cortical rim-supporting interbody device
US20180271576A1 (en) * 2013-06-24 2018-09-27 DePuy Synthes Products, Inc. Cortical Rim-Supporting Interbody Device
US20140378980A1 (en) * 2013-06-24 2014-12-25 Roman Lomeli Cortical Rim-Supporting Interbody Device
US20200352616A1 (en) * 2013-06-24 2020-11-12 DePuy Synthes Products, Inc. Cortical Rim-Supporting Interbody Device
US10806593B2 (en) * 2013-06-24 2020-10-20 DePuy Synthes Products, Inc. Cortical rim-supporting interbody device
US10758288B2 (en) * 2013-06-24 2020-09-01 DePuy Synthes Products, Inc. Cortical rim-supporting interbody device
US11224453B2 (en) 2014-07-08 2022-01-18 Spinal Elements, Inc. Apparatus and methods for disrupting intervertebral disc tissue
US11331198B2 (en) 2014-10-16 2022-05-17 Jmea Corporation Coiling implantable prostheses
US11672673B2 (en) 2014-10-16 2023-06-13 Jmea Corporation Coiling implantable prostheses and methods for implanting
US10751195B2 (en) 2014-10-16 2020-08-25 Jmea Corporation Coiling implantable prostheses
US9901457B2 (en) 2014-10-16 2018-02-27 Jmea Corporation Coiling implantable prostheses
US11638649B2 (en) 2014-11-04 2023-05-02 Spinal Stabilization Technologies Llc Percutaneous implantable nuclear prosthesis
US11633287B2 (en) 2014-11-04 2023-04-25 Spinal Stabilization Technologies Llc Percutaneous implantable nuclear prosthesis
US9592132B2 (en) 2015-01-09 2017-03-14 Shape Memory Orthopedics Shape-memory spinal fusion system
US11564811B2 (en) 2015-02-06 2023-01-31 Spinal Elements, Inc. Graft material injector system and method
US9987052B2 (en) 2015-02-24 2018-06-05 X-Spine Systems, Inc. Modular interspinous fixation system with threaded component
US11426290B2 (en) 2015-03-06 2022-08-30 DePuy Synthes Products, Inc. Expandable intervertebral implant, system, kit and method
US11596517B2 (en) 2015-05-21 2023-03-07 Musculoskeletal Transplant Foundation Modified demineralized cortical bone fibers
US10531957B2 (en) 2015-05-21 2020-01-14 Musculoskeletal Transplant Foundation Modified demineralized cortical bone fibers
US9775712B2 (en) 2015-06-30 2017-10-03 University Of South Florida Osteoconductive and osteoinductive implant for augmentation, stabilization, or defect reconstruction
WO2017003461A1 (en) * 2015-06-30 2017-01-05 University Of South Florida Osteoconductive and osteoinductive implant for augmentation, stabilization, or defect reconstruction
US10987448B2 (en) 2015-06-30 2021-04-27 University Of South Florida Osteoconductive and osteoinductive implant for augmentation, stabilization, or defect reconstruction
US9913727B2 (en) 2015-07-02 2018-03-13 Medos International Sarl Expandable implant
US11576793B2 (en) 2015-09-01 2023-02-14 Spinal Stabilization Technologies Llc Implantable nuclear prosthesis
US10575967B2 (en) 2015-09-01 2020-03-03 Spinal Stabilization Technologies Llc Implantable nuclear prosthesis
US10034768B2 (en) * 2015-09-02 2018-07-31 Globus Medical, Inc. Implantable systems, devices and related methods
US10485897B2 (en) * 2015-10-12 2019-11-26 Erik Erbe Osteogenic and angiogenic implant material
US20170112959A1 (en) * 2015-10-12 2017-04-27 Erik Erbe Novel osteogenic and angiogenic implant material
US10857003B1 (en) 2015-10-14 2020-12-08 Samy Abdou Devices and methods for vertebral stabilization
US11246718B2 (en) 2015-10-14 2022-02-15 Samy Abdou Devices and methods for vertebral stabilization
CN107335127A (en) * 2016-04-28 2017-11-10 美敦力心血管股份有限公司 The method of medical treatment device and the balloon-expandable for covering medical treatment device
US11510788B2 (en) 2016-06-28 2022-11-29 Eit Emerging Implant Technologies Gmbh Expandable, angularly adjustable intervertebral cages
US11596523B2 (en) 2016-06-28 2023-03-07 Eit Emerging Implant Technologies Gmbh Expandable and angularly adjustable articulating intervertebral cages
US11596522B2 (en) 2016-06-28 2023-03-07 Eit Emerging Implant Technologies Gmbh Expandable and angularly adjustable intervertebral cages with articulating joint
US11141206B2 (en) * 2016-06-30 2021-10-12 Teknimed Bone substitute and independent injection system
US10744000B1 (en) 2016-10-25 2020-08-18 Samy Abdou Devices and methods for vertebral bone realignment
US10973648B1 (en) 2016-10-25 2021-04-13 Samy Abdou Devices and methods for vertebral bone realignment
US11058548B1 (en) 2016-10-25 2021-07-13 Samy Abdou Devices and methods for vertebral bone realignment
US11259935B1 (en) 2016-10-25 2022-03-01 Samy Abdou Devices and methods for vertebral bone realignment
US11752008B1 (en) 2016-10-25 2023-09-12 Samy Abdou Devices and methods for vertebral bone realignment
US10548740B1 (en) 2016-10-25 2020-02-04 Samy Abdou Devices and methods for vertebral bone realignment
US11344350B2 (en) 2016-10-27 2022-05-31 Dfine, Inc. Articulating osteotome with cement delivery channel and method of use
US10478241B2 (en) 2016-10-27 2019-11-19 Merit Medical Systems, Inc. Articulating osteotome with cement delivery channel
US10537436B2 (en) 2016-11-01 2020-01-21 DePuy Synthes Products, Inc. Curved expandable cage
US11116570B2 (en) 2016-11-28 2021-09-14 Dfine, Inc. Tumor ablation devices and related methods
US11026744B2 (en) 2016-11-28 2021-06-08 Dfine, Inc. Tumor ablation devices and related methods
US10470781B2 (en) 2016-12-09 2019-11-12 Dfine, Inc. Medical devices for treating hard tissues and related methods
US10463380B2 (en) 2016-12-09 2019-11-05 Dfine, Inc. Medical devices for treating hard tissues and related methods
US11540842B2 (en) 2016-12-09 2023-01-03 Dfine, Inc. Medical devices for treating hard tissues and related methods
US10888433B2 (en) 2016-12-14 2021-01-12 DePuy Synthes Products, Inc. Intervertebral implant inserter and related methods
US10660656B2 (en) 2017-01-06 2020-05-26 Dfine, Inc. Osteotome with a distal portion for simultaneous advancement and articulation
US11607230B2 (en) 2017-01-06 2023-03-21 Dfine, Inc. Osteotome with a distal portion for simultaneous advancement and articulation
US10213321B2 (en) 2017-01-18 2019-02-26 Neuropro Technologies, Inc. Bone fusion system, device and method including delivery apparatus
US10973657B2 (en) 2017-01-18 2021-04-13 Neuropro Technologies, Inc. Bone fusion surgical system and method
US10111760B2 (en) 2017-01-18 2018-10-30 Neuropro Technologies, Inc. Bone fusion system, device and method including a measuring mechanism
US11497623B2 (en) 2017-01-18 2022-11-15 Neuropro Technologies, Inc. Bone fusion system, device and method including an insertion instrument
US10729562B2 (en) 2017-01-18 2020-08-04 Neuropro Technologies, Inc. Bone fusion system, device and method including a measuring mechanism
US10729560B2 (en) 2017-01-18 2020-08-04 Neuropro Technologies, Inc. Bone fusion system, device and method including an insertion instrument
US11141289B2 (en) 2017-01-18 2021-10-12 Neuropro Technologies, Inc. Bone fusion system, device and method including delivery apparatus
US11458029B2 (en) 2017-01-18 2022-10-04 Neuropro Technologies, Inc. Bone fusion system, device and method including a measuring mechanism
US11771483B2 (en) 2017-03-22 2023-10-03 Spinal Elements, Inc. Minimal impact access system to disc space
US10398563B2 (en) 2017-05-08 2019-09-03 Medos International Sarl Expandable cage
US11446155B2 (en) 2017-05-08 2022-09-20 Medos International Sarl Expandable cage
US11344424B2 (en) 2017-06-14 2022-05-31 Medos International Sarl Expandable intervertebral implant and related methods
US11690834B2 (en) 2017-06-23 2023-07-04 New York Society For The Relief Of The Ruptured And Crippled, Maintaining The Hospital For Special Surgery Composition, uses, and methods of treating spinal disc degeneration through sonic hedgehog signaling pathway
WO2018237368A1 (en) * 2017-06-23 2018-12-27 New York Society For The Ruptured And Crippled Maintaining The Hospital For Special Surgery Composition, uses, and methods of treating spinal disc degeneration through sonic hedgehog signaling pathway
US10940016B2 (en) 2017-07-05 2021-03-09 Medos International Sarl Expandable intervertebral fusion cage
US11896494B2 (en) 2017-07-10 2024-02-13 Life Spine, Inc. Expandable implant assembly
US11583327B2 (en) 2018-01-29 2023-02-21 Spinal Elements, Inc. Minimally invasive interbody fusion
US11471145B2 (en) 2018-03-16 2022-10-18 Spinal Elements, Inc. Articulated instrumentation and methods of using the same
US11419649B2 (en) 2018-06-27 2022-08-23 Illuminoss Medical, Inc. Systems and methods for bone stabilization and fixation
US11071572B2 (en) 2018-06-27 2021-07-27 Illuminoss Medical, Inc. Systems and methods for bone stabilization and fixation
US11744710B2 (en) 2018-09-04 2023-09-05 Spinal Stabilization Technologies Llc Implantable nuclear prosthesis, kits, and related methods
US11179248B2 (en) 2018-10-02 2021-11-23 Samy Abdou Devices and methods for spinal implantation
US11446156B2 (en) 2018-10-25 2022-09-20 Medos International Sarl Expandable intervertebral implant, inserter instrument, and related methods
US11510723B2 (en) 2018-11-08 2022-11-29 Dfine, Inc. Tumor ablation device and related systems and methods
US20200237356A1 (en) * 2019-01-30 2020-07-30 Ethicon, Inc. Surgical Delivery Devices for Meltable Bone Wax or Bone Putty
US11006937B2 (en) * 2019-01-30 2021-05-18 Ethicon, Inc. Surgical delivery devices for meltable bone wax or bone putty
US20200306052A1 (en) * 2019-03-29 2020-10-01 Medos International Sarl Inflatable non-distracting intervertebral implants and related methods
US11129727B2 (en) * 2019-03-29 2021-09-28 Medos International Sari Inflatable non-distracting intervertebral implants and related methods
US11925570B2 (en) * 2019-12-18 2024-03-12 Boston Scientific Scimed, Inc. Stent including anti-migration capabilities
US11883303B2 (en) 2019-12-30 2024-01-30 Vertebration, Inc. Spine surgery method and instrumentation
US11806245B2 (en) 2020-03-06 2023-11-07 Eit Emerging Implant Technologies Gmbh Expandable intervertebral implant
US11426286B2 (en) 2020-03-06 2022-08-30 Eit Emerging Implant Technologies Gmbh Expandable intervertebral implant
WO2021205357A1 (en) 2020-04-07 2021-10-14 Ethicon, Inc. Cortical rim-supporting interbody device
US11376131B2 (en) * 2020-04-07 2022-07-05 Ethicon, Inc. Cortical rim-supporting interbody device and method
US20220296387A1 (en) * 2020-04-07 2022-09-22 Ethicon, Inc. Cortical rim-supporting interbody device and method
US11857432B2 (en) 2020-04-13 2024-01-02 Life Spine, Inc. Expandable implant assembly
US11602439B2 (en) 2020-04-16 2023-03-14 Life Spine, Inc. Expandable implant assembly
CN111759532A (en) * 2020-07-07 2020-10-13 复旦大学附属华山医院 Do not rely on sacculus under shoulder peak of cyst wall leakproofness for long-term use
US11554020B2 (en) 2020-09-08 2023-01-17 Life Spine, Inc. Expandable implant with pivoting control assembly
US11918486B2 (en) 2020-12-07 2024-03-05 Samy Abdou Devices and methods for minimally invasive spinal stabilization and instrumentation
US11850160B2 (en) 2021-03-26 2023-12-26 Medos International Sarl Expandable lordotic intervertebral fusion cage
US11752009B2 (en) 2021-04-06 2023-09-12 Medos International Sarl Expandable intervertebral fusion cage
US11918483B2 (en) 2021-11-15 2024-03-05 Cogent Spine Llc Devices and methods for spinal stabilization and instrumentation

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