CA2391697A1 - Composite scaffold with post anchor for the repair and regeneration of tissue - Google Patents
Composite scaffold with post anchor for the repair and regeneration of tissue Download PDFInfo
- Publication number
- CA2391697A1 CA2391697A1 CA002391697A CA2391697A CA2391697A1 CA 2391697 A1 CA2391697 A1 CA 2391697A1 CA 002391697 A CA002391697 A CA 002391697A CA 2391697 A CA2391697 A CA 2391697A CA 2391697 A1 CA2391697 A1 CA 2391697A1
- Authority
- CA
- Canada
- Prior art keywords
- implant
- scaffold
- polymer
- ceramic
- lactide
- 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
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS 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
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L27/56—Porous materials, e.g. foams or sponges
-
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- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/40—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material
- A61L27/42—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material having an inorganic matrix
- A61L27/425—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material having an inorganic matrix of phosphorus containing material, e.g. apatite
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- A—HUMAN NECESSITIES
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- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/40—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material
- A61L27/44—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material having a macromolecular matrix
- A61L27/46—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material having a macromolecular matrix with phosphorus-containing inorganic fillers
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
- B29C—SHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING
- B29C44/00—Shaping by internal pressure generated in the material, e.g. swelling or foaming ; Producing porous or cellular expanded plastics articles
- B29C44/02—Shaping by internal pressure generated in the material, e.g. swelling or foaming ; Producing porous or cellular expanded plastics articles for articles of definite length, i.e. discrete articles
- B29C44/12—Incorporating or moulding on preformed parts, e.g. inserts or reinforcements
- B29C44/1214—Anchoring by foaming into a preformed part, e.g. by penetrating through holes
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- A61B17/064—Surgical staples, i.e. penetrating the tissue
- A61B2017/0646—Surgical staples, i.e. penetrating the tissue for insertion into cartillege, e.g. meniscus
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Abstract
A prosthetic implant having a tissue scaffold and a fixation device with a scaffold support and an anchoring post. The anchoring post extends from a surface of the scaffold support at a selected angle with the scaffold support embedded within the scaffold. The scaffold has a porous ceramic phase and a porous polymer phase. The polymer is foamed while in solution that is infused in the pores of the ceramic to create a interphase junction of interlocked porous materials and embedding the scaffold support portion of the fixation device.
The preferred method for foaming is by lyophilization. The scaffold may be infused or coated with a variety of bioactive materials to induce ingrowth or to release a medicament. The mutilayered porous scaffold can mimic the morphology of an injured tissue junction with a gradient morphology and cell composition.
The preferred method for foaming is by lyophilization. The scaffold may be infused or coated with a variety of bioactive materials to induce ingrowth or to release a medicament. The mutilayered porous scaffold can mimic the morphology of an injured tissue junction with a gradient morphology and cell composition.
Description
COMPOSITE SCAFFOLD WITH POST ANCHOR
FOR THE REPAIR AND REGENE1~ATION OF TISSUE
Field of the invention The present :invention re~#es generally to the field of tissue mpair and more particularly o composite caffold implants and scaffold fixation devices with post type anchors received in a hole formed in underlying tissue.
Background of the Invention Porous ceramic materials uch as hydroxyapatite, soluble glasses and ceramic forms have been used as scaffolds for the-ingrowth of tissue due to compositional and morphological biocompatabi!'rty. For example, the porosity of is such materials promotes cell 'infiltration.: A variety of methods are used to prepare porous ceramic scaffolds (prostheses);; uch as hydrotherrrtally treating animal bone or coral, burning off polymer beads mixed into a ceramic body, vapor deposition on fioarn, in~itratitm of polymer foam with a ceramic slip and foaming a ceramic slip.
ao One limitation exhibited by porous ceramic materials is their inherent britgeness. Attempts to address this limitation have included back=Riling a ceramic foam with monomer solutions of PMMA or PLA, draining excess solution from the ceramic foam there polymerizing through curing and/or drying in order to impart some toughness to he ceramic foam. Others have proposed 25 laminating oiid or porous polycraeric layers o a ceramic foam structure.
independent from: proposed: uses' in combination with ceramics, polymeric foams. have utility - in the repair and regeneration of tissue. For example, amorphous; polymeric foam has been used to fill voids in bone.
Various rnethods have been explored for preparing the poiyme~ foams; using;
so e.g.. leachabies; vacuum foamirn, g techniques; precipitated polymer gel masses;
and polymer melts with fugitive compounds that sublime at temperatures greater than room temperature. The ~fom~atfon of biocompatible: absorbable foams by lyoph'rlization is discussed in a copending patent application entitled 'Porous Lt ' ' Tissue Scaffoldings for the Repaid and Regeneration of Tissue", assigned to Ethicon, Inc.; docket number 091345096, flied June 30, 1999, hereby incorporated byreference.
Hinsch et al: (EPQ274898)- describes a porous open oeli foam of s potyhydroxy acids for the in. grovi~th of blood ~essets and cells. The foam can be reinforced with fibers, yams; braids, knitted fabrics;: scrims and he like.
Athanasiou et al. (U~S: Patent No. 5,607;474) have proposed using a two-layer polymeric foam device for n:pairing osteochondraP defects at a location where two dissimilar types of tissue are present. The two polymeric lo , layers are prepared separately, arid joined together at a subsequent step. Each of the layers is designed to have stiffness and cornpressibitity values that correspond respectively to cartilage and bone tissue, mimicking the cartilagelbone interface. However, the Athanasiou device exhibits an abrupt change in properties from one hyer to the next, whereas the juncture of cartilage i5 and bone displays a gradual transition; with cartilage: cells gradually ganging welt morphology and orientation depending on the location relative to the underlying bone structure: f=urther; collagen fiber orientation within the matrix also d~anges relative ~ its location: in the structure.
H. Levene et al., U.S: Patent No. 6;103,255 describes a process zo used for making a scaffold having a ubstantuaily continuous polymer phase with a distribution of laroge and small pore sizes; with the small pores contained in the walls of the large pores.
tn a study done by G. Niederauer et al. and reported in Biomaterials 21 (2000) 2561; scaffolds for articular cartilage repair were as prepared from layers of polylacticlpalyglycolic acid (PLG) and polylacticJpoiyglycoiic aad reinforced with fibers of the same material, bioglass or calcium sulfate: The PLG layer was made porous in all cases by expanding a precipitated ge! mass of polymer under vacuum at elevated. emperatures. The reinforced layers were made porous in a similar fashion after incorporating the reinforcement. in the polymer solution and prior to precipitation of the polymeric get mass. Once the two layers were fabricated, they were adjoined using a srrtali amount of sowent to glue the two layers together:
t x The use of a porous polymer for the purpose of engineering cartilage is described in the patent by T. Mahood et ai., (EP1027897A1 ) which discloses a mufti-layer polymer scaffold in which the layers are attad~ed by sucxessive dip coating or by the attachment of the two layers to a third. The s third layer is described as a barrier to cell-diffusion, thus co(ifining chondrocytes to the polymer layer and osteobiasts, to the ceramic layer.
Krekiau et al. in 8iomatecials 20 (1999) 1743 have evaluated a fibrous polymeric fleece attached to a porous ceramic material, for the purpose of culturing chondrocytes in the polymeric caffold while simultaneously ?o providing a bone formation inducing absorbable material to simulate articular cartilage. In this study, a fibrin-.cell-solution was used to affix the :ceramic and polymeric: layers by way of encapsula#~ with the intent that.the phases would interact in vitro in order to create a ,mechanically stressabie junction. The authors discuss the possibility of providing: the surfaces of the layers with teeth to increase shear strength. However; there is no mechanism by which the two dlffererat layers are interlocked #c resist delaminating forces in directions perpendicular to the laminate function and there is an abrupt transition beiween the two ,layers. .
In addition to the limitations of the prior art relative to the composition and morphology of tissue scaffolds, the fixadon of the scaffold at the site of injury remains challenging: Various fixatiota methods have been explored, including press-fitting the scaffold into the defect (which may result in slippage or destrudaon of the implanted scaffold) or suturing the scaffold to the periosteai flaps. The tatter approach is not always ideal because the geometry of the as scaffold may not match that of the periosteal flaps or the flaps may have been destroyed or cannot be located:
.It would therefore be advantageous to overcome the above mentioned limitations with a scalffold that provides secure attachment to a defect site.
Summarv.of the Invention The limitations: of the prior art are solved by the present invention which includes a-prosthetic implant having a tissue caffoid and a.fixation device s with a scaffold support and an anchoring post: The anchoring post extends from a surface of the scaffold support at a selected angle with the scaffold support embedded within the scaffold.
Brief Description of FiQUres Figure 1 is a top perspective ~riew of an implant in accordance with an exemplary embodiment of the present invention.
Figure 2 is a aottom perspective view of the implant of Figure 1.
~s Figure 3 is a cross-sectional view of the implant of Figures 1 and 2.
Figure 4 is a cross-sectional view liic$ Figure 3 of an alternative embodiment of the present inventiocy:
2o Figure 5 is a diagrammatic cross sactionai view of the implant of Figure 4 within a rnofd for fabrica~ng-,the mplant.
Detailed Description of the Invention This invention includes an impiantable device with ~ a scaffold as component and a frxation component for mechanically holding the scaffold component in position relative vto a tissue defect to be repaired. The scaffold component is formed around a scaffold support platfomn of the fi~cation component and has a porous biocompatible polymer layer attached to a porous ceramic layer via a porous transitional interface: The scaffolds are particularly s o useful in the repeirlfegeneration of defects present at a, junctiory of tissue types . exhibiting a transitional or gradient morphoiogylphysiology such as at the cartilagelbone junction: The present invention can be utilized to a repairlregenerate a issue junction-by inducing one cell type to proliferate in the polymer phase of the scaffold and a second ceN type to grow in the ceramic phase of the scaffold. Examples of such junction regeneration sites are (a) spinal disc (nuclear and annular cells cultured on tire polymer, phase aid s osteoblasts cultured in the ceramic phase; (b) articuiar or meniscal cartilage (chondrocytes or fibrochondrocytes, respectively, cultured on the polymer phase and osteoblasts cultured in the :ceramic): The present invention may also be utilized to repair the meniscus,. fibrocattilage, tendons, and ligament. The features of the porous polymer phase can be controlled to suit a desired application by choosing the aQpropriate ~ conditions during the process of lyophilization, or freeze drying. The porous polymer foam can be directly lyophilized into the ceramic fracture creating a multiphasic material composed of a polymer foam with or inithout reinforcement structures, an interphase zone of polymer foam diffused within end interlodcingwith theporous ceramic, and the porous ceramic. A portion of the° l3xation component may be placed between the polymer and oerarr~ic layers, which are structurally integrated to resist detachment of the scaffold component. from the fixation component and/or delamination of the composije scaffold under in uivo conditions. The implant may be partially or completely absorbable:
The interphase zone exhibits a micxoporous polymer foam located within the macn~pores of a poFOUS ceramic. The interpenetcation of the two porous layers creates a strong mechanical junction while simultaneously pcovidinga gradual change in material properties for the purpose of regenerating different tissues or oo-culturing different types of cells in inmate contact with one another. The interconnecting pores and channels facilitate the transport of nutrients and/or invasion of cells into the scaffold; facilitating the ingrowth of tissue and more closely mimicking naturally ' ocxufring (issue junctions. The present. invention therefore faci~tates ~ltutar organization and the regeneration of tissue junctions with normal morphology and physiology. The composition 3o and features of the scaffold 20 are deibed in a copending Application fled , contemporaneously herewith, enfitied; "Porous CeramiclPorous Polymer Layered Scaffolds for the Repair and Regeneration of Tissue, (Serial No. to be v , assigned) and assigned to the present assignee; such application being incorporated by reference herein.
The: features of: a scaffold irt accordance with. the present invention can be tailored to suit a particular applica#ion by selecting the appropriate s ceramic, polymer and conditions for iyophifization of the polyriaer to obtain one or more of the following properties: (1 ) inferconnec~ng polymer foams attached to the porous ceramic (2) a variety of poros~ties ranging from about 20% to about 98°~ for the :polymer foam; (3) a gradient in the pore size between the polymer and ceramic-, (4) channels that nm through the porous polymer foam for improved cell invasion, vascularization and nutrient diffusion; and (5) micro-patteming of pores or the addition of other polymer structures on the surface of the polymer for cellular organization or to limit cellular invasion.
in addition, ttie scalffotd can include (1 ) porous ~mposifies with a composition gradient to elicit or, tatce advantage of. different cell response to ~s different materials; (2) reinforcement with knitted; braid; woven; or non-woven fabrics or' meshes; or truss strt~cterres in ordef to impart desired mechanical properties; (3) blends of different polymer compositions to create a potymer phase that has portions that <will break down at different rates; (4) multi-layer composite structures with layers of ;alternating porous ceramics and polymers;
Zo (5) a polymer phase co-lyophilized or coated with pharmaceutically active compounds; (6) a ceramic phase coated with pharmaceutically active compounds such as growth factors and/or (7) cells which may be cultured prior to or at the time of implantation. .
Referring to Figures 1 through 4, the implant 10 includes a scaffold is component 20 and a fixation component 30 (See Figure 3). Scaffold component 2t3 has ;polymeric phase Z2 arid ceramic phase 24; which are mechanically interlocked at interphase region 26: Polymeric phase 22, ceramic phase 24, and interphase n3gion 26 preferably have pores 23, 25, 27,' respectively, with an open cell structure. As shown in Figure 3; fixation component 3D includes scaffold support 32 and anchoring post 34. Though not shown in the figures;
anchoring post 34 may feature' ribs, aerrations; or other surtace roughness or engagement features that improve the attachment of anchoring post 34' to the implant site; e.g., a hole in bone tissue. A preferred f~cation component for use ~ 02391697 2002-06-26 in the present invention is described in U.S: Patent Application Seria( No.
091793,029; entitled, "Scaffold Fiacation Device For Use In Articular Cartilage Repair", filed on 2126L01, assigned o the preserit assignee and which is hereby incorporated herein by reference.
s . The implant 10 must have structural integrity to facilitate ease of handling iy an operating room environment, i.e.scaffold component 20 and fixation compon~nt 30 must not separate before, during; or after the surgical procedure. Adequate strength and: :physical properties ale developed in the-implant through the selection of materials used to form the scaffold 20 and fixation 3Q components, and fihe manufacturing process.
As shown in Figures 3 and 4, the scaffold component 20 fully .
encapsulates scaffold support 32 -of the frxation component 30. This encapsulation serues as ttie means of attaching the scaffold component 20 to the fixation component 30: Figure 3 shows scaffold support 32-of the fncation i5 component 30 embedded in the polymeric phase 22 with the lower surface 31 abutting the interphase region 26. to a preferred embodiment shown in Figure 4, scaffold support 32 of the fixation component 30 is fully encapsulated in all three components 22! 24; 26 of scaffold component 20. This is achieved by fully or partially countersinking scaffold support 32 in ceramic phase 24.
zo The infusion of the polymeric phase'22 into the ceramic phase24 securely fastens the finro phases 22;=24 and supports the brittle structure of the porous ceramic phase 24. The polymer 22 acts as a cushion to dissipate impact energy to shield the brittle ceramic 24 from ca#astrophically damaging Stresses:
In addition; the communicating . pores 23; 25, 2? encourage the growth of zs different types of Ails, promoting the regeneration of different adjoining layers of .
tissue at an injured tissue junction.
.The pores 25 in the ceramic phase 24 are interconnected, and may be selected to have pore sizes ranging from 25 to 600 microns, preferably from 100 to 250 microns. The pores 23 in the polymeric phase 22 are also s o interconnected and range in size from about 10 to 250 microns, preferably 30 to 150 microns. The temps "micropore" and "macropore":may be used to designate the tH/O $iZe Scales Of pOre$ 23; 25 found in the scaffold 10. If the bridle ceramic phase 24 is cracked, the polymeric phase 22 in the ihterphase region 2s holds f ' the caffold component 20 together. The composite scaffold component 20 facilitates the creation of a strong bond between different types of tissue such as in the repair and regeneration of articular cartilage, meniscus, and spinal discs.
The embedding of fixation component 30 within he scaffold s component20 minimizes their combined hickness minimizing the depth of the hole in the tissue made to receive the implant 10 and the assvaated damage o the tissue proximate to the defect. In addition, ceramic phase 24 of scaffold component 20 (in conjunction with the polymeric phase 22j provides support to the hard tissue surrounding the implant, minimizing the likelihood of the collapse io , of hard tissue in the region of implant device 10; as well as facilitating the regeneration of minerali2ed hard tissue (bone).
The implant device 10 may be' fabricated by feeding anchoring post 34 of fixation component -30 through a hole in ceramic phase 28 . such that scaffold support 32 rests on top of, or in a countersunk region of, ceramic phase ~s 24. This assembly is then partially introduced into a polymer solvent system allowing he polymer-solvent system to infiltrate into he porous ceramic phase.
The polymer phase 22 is then foamed: The desired polymers may be foamed by lyophiiization, supercritical solvent foaming. (i.e., as: described in EP
4fi416381 ), gas injection extrusion; gas injection molding or casting with an extractable zo material (i.e., salts, sugar or any other means known to dose skilled in the art):
It should be appreciated that the scaffold support 32yrnay have openings therein through which the polymer 22 mar contact fhe ceramic 14 it is preferred to foam the polymer :22 by lyophilization, or freeze drying: Suitable methods for lyophilizing elastomeric polymers to form foams is 2s described in the following examRie and in: the peeing U:S: patent applications entitled, "Process for Manufacturing Biomedical Foams°, Serial No;
09/345095, flied June 30, 1999 and 'Pcirous Tissue Scaffoldings for the Repair or Regeneration of Tissue"; Serial No091345098; filed June 30,1999, both assigned to Ethicon, Inc. and hereby incorporated, herein by reference.
30 Figure 5 illustrates a molding apparatus 50 having mold 52 and support bracket 54. Support bracket 54 includes a hrougfi note 53 which is aligned over the well 55 of motdr52. A hotder 40; having :head 42 and pin 44, may be used to hold fixation component 30: Pin 44 passes through hole 53 with head 42 abutting support bracket 54. Pin 44 inserts into bore 46, holding fixation components 30 over the welt 55 penclt~tousty; by a fricfion fit:
Palymes-solvent,syetem 28 is infused into the vNeN 55 ofimoid 52, .to a level such that polymer solvent system 28 contacts veramic phase 24.
s Polymer solvent system 28 is of love viscosity and wicks via capillary action into ceramic phase pores 25. Other methods of infiltrating include, but are not limited to, injecting the polymer-soiventaystem into the ceramic 24 under pressure and vacuum assisted inftltration. - The orientation of 5xation component 30 within the polymer-solvent system 28 determines the orientation of the fixation component 30 within imptanf 10: Although the: means of aligning fixation component 30 in the welt 55 of mold 52 include support bracket 54 anti a fricfion fit between connector pin 44 of holder 40: and fixation component 30, other means to accomplish the same objective ;should be readily apparent to one skilled in the art. The mold 52 can be made from any material that does not chemically react ~s with the polymer-solvent system 28 and is preferably formed from a heat conductive material.
The molding apparatus 50 is ptaced in a lyophilizer (freeze :dryer).
to undergo directional cooling through the wall of mold 52 that is in contact with the lyophilizes shelf, which is subjected to a thermal cyde. The heat transfer ac front moves upwards from: the lyophilizes shelf through the mold wall into the polymer solvent system 28. lAilhen the temperature of the polymer solution goes below the gelation andlor freezing point, 1t separates into polymer and solvent phases giving rise to the ceillfoam structure:
The pore morphology that ~ results from the freezing step is a is function of solution thermodynamics, freezing rate, temperature to~ which it is ~oied:; concentration of the solution, the presence of reinforcement elements, the presence of an adjoining layer, he . occurrence of t~mogeneous or heterogeneous nucleation etc. Detailed descriptions of these phase separation phenomena are known In the art and can ' be found in the references "Microcellular foams via phase eparation" by A: T. Young, J. Vac: Sri.
Technol., A 4(3),'Mayl;Jun 1986; and "Th~errnodynamics of Formation of Porous Polymeric Membrane from Solutions" by S'. Matsuda, Polymer J. 23(5), (1:991 ) 435. The lyophiiization process can therefore be used to bond the polymer and ceramic layers 22; 24 while simultaneously creating a composite material with the correct pore structure to regenerate- tissue.
The porous ceramic phase 24 of the scaffold may be composed of mono-, di-; tri-, a-tci, a-tri, and tetra-calaum phosphate, hydroxyapatite, fluoroapatites; calcium sulfates, catdum fluorides; ~Iautr~ oxides, calaum carbonates; magnesium calcium phs~sphates, bioglasses; and mixtuies thereof.
There are a number of suitable porous biocorypatible ceramic materiats currently available on the commercial market uch as Surgibone (Unilab Surgibone; Inc., Canada), Endobon (Merck Biornaterial France, France); Ceros (Mathys, A. G., io . Bettiach; Switzerlandj, and interpore (interpose, Irvine: CA, United States):
Alternatively, the ceramic phase 14 may be in the form of a porous polymer matrix with indusions of short ceramic fibers or particutates. This alternative ceramic phase 14 ray be formed: by vonventional methods fior working plastics, such as injection molding; with the porosity ther~f provided by is teachable inclusions, molds with pore forming pins, or drilling.
The polymeric phase 22 may be either a natural or synthetic polymer, or combinations of both: Natural biopotymers include collagen;
elastin, alginate, chitin, hyaluronic acid, and others. Examples of suitable synthetic biocompatible, bioabsoFbable polymers that oouki be used include aliphatic ao polyesters, poiy(araino aads), copoly(ether-esters); polyalkylene oxalates, polyamides; poly(iminocarbonates), polyorthoesters, potyoxaesters, polyamidoesters, polyoxaesters containing amine groups; pofy(anhydrides), polyphosphazenes, biomotecules; and blends thereof.
For the purpose of this- inverytion aliphatic polyesters include but 25 are not limited to homopolymers and copolymers of testicle (which includes lactic acid, D-;L- and meso testicle), gtycolide (including glycolic acid), E-caprolachone, p-dioxanone (1,4-dioxan-2-one); trirnethylene carbonate (1,3-ciioxan-2-one);
alkyl derivatives of trimethyiene cafbonate, &vaterolacton~e~ ~-butyroiacto~ne, butyrolactone, ~-decalactone, fiydroxybutyrate, hydroxyvalerate, 1,4-dio~cepan-30 one (including its dimer 1,5;8,12,tetraoxacyciotetradecane-?,14-dione), 1;5-dioxepan-2-one, 6,6-dimethyt-1,4-dio~can-2-one; 2,5-diketomorpholine;
pivalolactone, alpha, alpha-diethyipropiolactone, ethylene carbonate; ethylene oxalate, 3-methyl-1,4-dioxane:2,~-dione: 3,3-diethyl-1,4-dio~can-2;5-dlone, 68-dioxabicydoctane-7-one and polymer blends thereof:
Poly(iminocarbonates) for the purpose of this invention include those desrcxibed by Kemr~itzet and Kohn, in the Handbook of Biadearadable s Polymers; . edited by Domb; . Kost and Wisemen, Hardwooii Academic Press, 1997; pages 251-272. Copoiy(ether-esters) fvr fhe purpose of this invention include those oopoiyester-ethers described by Cohn and Younes J. Biomater:
Res., 22, :(198$) 993, and Cahrt; Polymer Preprirris, 30(1), (1989) 498. .
Polyalkylene oxalates for the pWrpose of this invent~n include ~o , those described in U.S. Patent Nos: 4,208,511; 4,141,087; 4;130,639;
4,140,678; 4;105;034; and 4,205,399-(incorporated by reference herein).
Potyphosphazenes for the purpose of his invention include cc-, ter- anti higher order mixed monomer basal polymers rriade from L-tactile; D,L-lactide, lactic acid, giycolide, glycoiicv acid; para-dioxanone, trirnethytene carbonate and s-caprofactone those described by Allcock in The Encuctopedia of Polymer Science, ~ley lntersciences, John Wiley & Sons, 13 (1988) 31, and by Vandorpe, Schacht, Dejardin and .Lenvnouchi in the Handbook of Biodecaradable PWy-mess; edited by Domb, Kost and WisemerrHardwood Academic Press, (1997) 161 (which are hereby incx~rporated by reference herein).
ac Polyanhydrides for the purpose of this invention indude those from diacids of the form H40C-C6H4-O-(CH~~"-O-CBH4-COOH where m is an integer in the range of from 2 to 8 and copolymers thereof with aliphatic alpha-omega . diacids of up to 12 carbons.
Poiyoxaesters, polyoxaamides and polyoxaestets containing as amines andtor arr~ino groups for the purpose of this' invention include those described in one or more of the failowing U:S. Patent Nos. 5;464,929;
5,595;751;
5;597,579; 5;607,fi87; 5,618;552; 5,620,698; 5;645,850; 5,648,088; 5698,213;
5,700,583;: and 5;859,150 (which are incorporated herein by reference).
Polyorthoesters for the purpose of this invention include those described by Helier in the Handbook of Biodegradable Polymers, edited by Domb, Kost and Wisemen; Hardwood Academic Press, (1997), 99 (hereby incorporated herein by reference).
Aliphatic polyesters are preferred for making he polymer phase 22:
Aliphatic polyesters can be Momopoiymers; copolymers (random, block, segmented, tapered blocks, graft,; triblodcetc.) having a linear, branched or star structure: The preferred morphology ofi the: copolymer chains is linear:
Suitable s monomers: for making aliphatic hornQpolymers and copolymers may be selected from the group consisting of, but not limited to, lactic acid; lactide (including L-, D-, meso and D;L mixtures), giycolic acid, glycolide, E-caprolactone, p-dioxanone (1,4-dioxan-2-one), trimethyier~e carbonate. (1;3-dioxan-2-one), delta-valerolactone, beta-butyrolactona, epsilon-decalactone, 2,6-diketomorphoiine, pivalolactone, alpha, alpha-diethylpropiolactone, ethylene carbonate, ethylene oxalate, 3-methyl-1,4-dioxane-2,5-dione, 33-diethyl-1;4-dioxan-2;5-dione, gamma-butyrolactone, 1;4-dioxepan-2=one, 1,5-dioxepan-2-one; 6,6-dimethyl-dioxepan-2-one, 6,8-dioxabicyclo~tane-7-one and combinations thereof.
Etastomeric cop~lyrjtiers also are particu(ariy useful in the present ~s invention. Suitable bioabsorbable, biocompatible elastomers include, but are not limited to, those selected from the group consisting of eiastomeric copolymers of s-caprolactone and glycolide (preferably having a mole ratio of e-caprolactone o glycolide of from about. 35:65 .to about fi5:35, more preferably from 45:55 to 35:65); eiastomeric copolymers of ~-caprolactone and lactide; -including L-lactide, D-lactide blends thereof oc tactic acid copolymers (preferably having a mole ratio of s-caprolackone to lactide of from about 35:65 ~ to about 65:35 and more preferably from 45:55 to 30:70 or from about 95:5 to about 85:15); elastomeric copolymers of p-dioxanone (1,4-dioxan-2-one) and Iactide including L-lactide;
D
lactide and lactic-aad (preferably having a mole ratio of p-dioxanone to lactide of is from about 40:60 o about 60:40); elastameric copolymen,:of E~proiactone and p-dioxanone (preferably having a: mole ratio of ~-caprolactone to ;p-dioxanone of from about from 30:70 to about 90:30); elastomeric copolymers of p-dioxanone and trimethylene carbonate (preferably having a mote ratio of p-dioxanone to trimethylene carbonate of fnam about 30:10 to about T0:30); eiastomeric ao ~poiymers of trimethylene carbonate and giycolide (preferably having a mole ratio of trime#hyiene carbonate to giycolide of from about 30:70 to about 70:30), elastornerie copolymer of trimethylene carbonate and lactide including L-lactide, D-lactide, blends thereof or lactic acid copolymers (preferably having a mole ratio of trimethyfene carbonate to lactide of from about 30:70 to abcaut 7U:30);
and blends hereof. Examples of suitable bioabsorbable elastomers are also described in U:S: Patent Nos. 4,045:;18, 4,057;537 and 5,468;253, al( hereby incorporated by reference.
s In the preferred embodiments of his invention, ~ the elastomer from which the foams are formed will exhibit a percent elongation greater than about 200 percent and preferably greater than about 500 percent. The properties that determine the degree of elasticity of'the bioabsarbable etastomer are achieved while maintaining a tensile strength greater than about 500 psi, preferably greater than about 1 X000 psi, and a tear strength of greater than: about 50 Ibsrnch, preferably greater than about 80 Ibsiinch. , The polymer or copolymer suitable for forming the polymer phase 22 for any particular application depends on sevefal factors. The chemical composition, spatial dis#ribution of the phases, 'the molecular weight of the is polymer and ~e degree of crystallinity; all dictate to some >extent the in vitro and in vivo behavior of the poiymec.'However, the selection of the polymer to make foams for tissue regeneration largely d$pends on (but is not limited to) the following factors: (a) ,bioabsorpt'ron (or biodegradation) kinetics; (b) in vivo mechanical- performance; (c) ceN response to the material in terms of cell ao attachment; proliferation, migration and differentiatiort and (d) biocompatibility.
The ability of the polymerphase to resort in a timely fashion in vivo is critical. The differences in the: absorption time under in yivo conditions caa also be the basis for combining two different copolymers: For example, a copolymer of 35:65 s-caprolactorie and vglycolide (a relatively fast absorbing as polymer) is blended with 40:60 e-caprolactone and (L)lactlde copolymer (a relatively low absorbing polymer) to form ' a foam. Such a foam could be processed to yield several different physical structures depending upon the technique used. The two phases can be either: randomly inter-connected bicontinuous phases, or have a gradient or laminate composition with an integrated interface between the phase layers. ' The microstructure of these foams cart be optimized to regenerate or repair the desired anatomical features of the tissuethat is being engineered.
Suitable solvents for the preferred absorbable :aliphatic polyesters that will not affect the ceramic foams include but are got limited to sohrents selected from a group consisting of formic acid, ethyl formats, acetic acid, hexafluoroisopropanol (HF1P);cyc~ic ethers (i.e. THF, DMF; and PDO); acetone;
s acetates of C2 to C5 alcohol (such as ethyl acetate and t-tiutylacetate), gtyme (i.e. monoglyrne; ethyl glyme, diglyme, ethyl diglyme, triglyme, butyl diglyme and tetraglymej methylethyl ketone, dipropyleneglycol methyl ether, lactones (such as ~vaierolac~one; S-valerol~c~one(i-butyrota~one, y: butyrolactone) 1;4 dioxane; 1,3-dioxolane, 1,3-dioxolane 2~ne (ethylene c~rbonatej, dimethlycarbonate; diethytcarbonate; benzene, tc~uene, , benzyl alcohol, p xytene, naphthalene, tetrahydrofuranN-methyl pyrrotidone, dime~ylformamide;
chloroform,; 1,2-dicfiloromethane; morpholine; dirnethylsulfoxide, hexafluoroacetone esquihydrate (HFAS), anisoie and mixtures thereof. Among these solvents; the preferred solvent is 1,4-dioxane. A homogeneous solution of ns the polymer in the solvent is prepared using standard echniques:
Additionally; polymer solvent system 28 can be solidified with various reinforcements such as . films, scrims, woven, nonwoven, knitted or braided textile structures incotporated therein: In addition fio attenng he n~qhanicaf properties of the polymer 22, reinforcements can be utilized: (i) to ao modify the in vitro behavior of the polymer. 22, e.g., by introducing a different in vitro profile; (ii) as a canier for the contfolled release of a dnrg; anti (iii): as a carrier for Micro-Electro Mechanicat ~xsterns (MEt~IS).
Solids may be added to the polymer-solvent system 28 during,the processing -of the implant 10 to. act as buffers, reinforcing materials, porosity as modifiers; andlor radio~paque markers to allow imaging after implantation.
Suitable solids include, but are not limited; to, particles of demineralized bone;
calcium phosphate particles, calaurn cerbanate particles for bone repair;
teachable solids for pore creation and- particles of bioabsorbable polymers not soluble in the solvent system as reinfording agents or fio~ the creation of pores as tney aye absorbed:
Suitable teachable solids include but are not limited to nontoxic teachable materials such as ~sa#ts (ie., sodium ctfiloride, ;potassium chloride, calcium chloride, sodium tartra#e, sodium citrate; and the like).
biocompatible mono and disaccharides (i:e.; glucose, fructose, dextrose, maltose; lactose and sucrose), polysaccharides (i:e:, starch, alginate); water soluble proteins (i.e:, gelatin and agarose) and paraffin: .Generally all of these roateriais ~vitf have an average diameter of fens han about 1 mm and ,preferably will have an average s diameter of from about 50. to about 500: tem. The particles will generally constitute from about 1 to about 50 uolurt~ percent of the total volume of the particle and poiymec safvent mixture (wherein the total volume percent equals 100 volume percent). , .The teachable materials can be reranove~d~ by immersing the foam with the teachable material in a solvent in which the particle is soluble io : for a sufficient amount of time to allow leaching of subs#anfiaity ati of the particles, but which does not dissolve or detrimentally alter the foam. The preferred extraction solvent is water, most preferably distilled-deionized water.
This process is described ~ in tJ:S. Patent No. 5;514;378, hereby incorporated herein by reference: Preferably the foam will be dried-after a leaching process is is complete at low temperature and/or vacuum dried to minimize hydrolysis of the foam unless accelerated absorption of the foam is desired.
Various proteins (including short chain peptides), growth agents, chemotatic agents and therapeutic agents (antibiotics; analgesics; anti-inflammatoties, anti-rejection (e.g.: irnrnunosuppressa~ts) and anticancer dn~gs), zo or ceramic particles can be added to the composite scaffold . 20 during processing Qr adsorbed onto the surface or back-felted into the scaffold 20 after fabrication. The pores 25 of the ceramic phase 24 andlor the pores 23 of the polymer 22 may be partially or completely filled with biocompatible resorbabie synthetic :polymers or polymers (such as~ collagen or elastin} or biocompa#ible 25 ceramic materials (such as hydroxyapatite) and combinations thereof (that may or may not contain :materials that promote tissue' growth). Suitable materials include but are not limited to autograft, atlograft, ar xenograft bone, bone marrow; morphogenic proteins (BMPs); epidermal growth factor (EGF), frbroblast growth facfior (FGF)platelet derived growth factor {PDGF); insulin derived 3o growth factor (!GF-i and lGF-li), transforming growth factors (TGF-p), vascular endothelia growth factor (VEGF), platelet rich plasma (PRP) or other osteoinciuctive or osteoconductive rr~aterials known in the art: The polymer fillers could also be conductive or _chemotactic materials; or delivery vehicles -for growth factors: Examples would be recombinant or animal derived collagen or elastin or hyaturonic acid.
Bioactive coatings or surface treatments could also be applied to the surFace of the implant 10. For example; bioactive peptide sequences s (RGDsj could be applied to faciii~ate protein adsorption acrd subsequent cell tissue attachment.
Therapeutic agents may also be delivered via the implant 10. The polymers and blends that are used to form the scaffold 20 can contain therapeutic agents. Far example, polymer 22 could be mixed with a therapeutic agent prior to forming the composite scaffold 20 or loaded into the scafifold after it is formed: The variety of different therapeutic agents that can be used in conjunction with the implant 10 of the present invention is vast. In general, therapeutic agents which may be administered via ttie implant 90 include; without limitation:
antiinfec~ives such: as ant~iotics and antiviral agents; chemotherapeu#ic agents (i:e:
anticancer agents); anti-rejection agerfts; analgesics ::and analgesic combinations; anti-inflammatory agents; hormones such as steroids; growth factors (bone morphogenic proteins ti.e. BMPs 1-?), bone morphogenic-like: proteins (i.e.
GFD-5, GFD-? and Gf=D-8); epidermal growth factor (EGt=), flbroblast growth factor (i:e. FGF 1-9j; platelet derived growth factor (PDGFj, , insulin; like gfowth factor ao (iGF-! and fGF-il), transforming growth factors (i.e. TGF-~ i-111), .
vascular endothelial growth factor (V~GFjj; and other naturally derived or genetically engineered :proteins, polysaccharides, glycoproteins, ~r iipoptaoteins: These factors are described in The Cellular and Molecular Basis of Bone Formation and Re air by Vicki Rosen and R. Scott Thies, published by R:G. Landes Company a hereby incorporated herein by reference:
Composite scaffolds 20 containing bioactive materials may be formulated by mixing one or more therapeutic agents with the polymer used to make the polymer phase 22, with the solvent,-or with the polymer-solvent mixture that is then foamed via lyophiiization. Alternatively, a therapeutic agent may be o coated on the composite scaffold 20 with a Pharmaceutically acceptable carrier that does not dissolve the scaffold 2Q. The therapeutic agents; may be a liquid, a finely divided solid; or any other appropriate physical form: Typically, but optionally, the matrix will include one or more additives, such as diluents, carriers;
excipients;
stabilizers or he like. The type of pplymer and drug concentration can be varied ~to control the release. profile and the amount of-drug dispensed. Upon contact with body fluids, the drug will be released: if the drug is incorporated into the scaffold 20; then the drug is released as it undergoes gradual degradation (mainly s through hydroiysisj. This can resulk in prolonged -delivery (over, say 1 0 5,000 hours, preferably 2 to 800 hours) of~ effective amounts (say, 0:0001 mglkgfiour to mglkglhourj of the drug:
As outlined in Vacanti, U.S. Patent No. 5,??0,41 ?; cells can be harvested from a patient (before apt during urgery to repair the tissue) and he lo , cells can be processed under sterile conditions to provide a specific cell type (i.e., piuripotent cells, stem cells, ~rnarrow cells, progenitor human autologaus adipose tissue (PHAAT) cells or-precursor veils, such as; the mesenchymal stem cells described in Caplari; U.S: Patdnt No. 5,486;359). These veils, e.g., myocytes, adipocytes, fib~omyoblasts, ectodermal ceU, musvle cells; osteoblast is (i.e: bone cells), chondrocyte ~r:e. carkilage sails); endothelial ce~is, fibroblast, panvreatic veils; hepatocyte, bile duct cells, bone r~aarrow cells; neural veils;
genitourinary cells :(including nephritic cells). and combinations thereof rnay be applied or seeded into the porous composite caffold 20. Autogenous, allogeneic, xenogeneic cells maybe used. The veils may be cultured ex vivo so and then reimplanted. Tissue may be harvested from a patient, processed to select certain veils andlor growth factors, such asPRP (Platelet rich plasma), and then reimplanted with the implant 10 back into the patient. The implanted cells could also contain inserted DNA encoding a protein.that could stimulate the attachment, proliferation or differentiation of tissue.
Cells may be implanted into tip scaffold 20 by placing the scaffold in a veil culture such that the veils invade the micfopores 23. and macropores 25: The scaffold 2~ can then be implanted into the patient. The in vitro seeding of cells could provide for a more rapid development and differentiation process for the tissue. It is clear that cellular differentiation and :tee cxeation of tissue o specific extraceltular matrix is critical for the tissue engineerihg of a functions( implant: !t is known that different cell types (stromai cells and d~ondrocytes) can be cultured on different structures. A gradient stcuctuce also allows fog co-cultured tissue scaffolds 20 to be generated.
One use of the construct described herein is for the repair and regeneration of articular cartilage. A~ticular cartilage is an example of a naturally occurring structure ~nposecl of four different zones that indude the superficial or tangential zone within the first 10 20% of the stn:~ctur~e (this includes Hie s articular surface), the middle.zone, which is 40-GO% of he rniddle structure, the deep zone that is adjacent to the tide mark, :and a transition zone between the bone and cartilage that is composed of caldfceci cartilage: Subchondral bore is located adjacent to the tide mark: and this transitions into cancellous bone:
As described-above, the present invention permits the fabrication of a scaffold, e.g., 20 having multiple layers, each having its ~ own characteristics of composition, porosity, strength; etc, Accordingly; the scaffold, e.g., 20 may act as a ternptate for multiple distinct tissue zones as are present in articular cartilage.
The surface porosity of the polymer phase 22 can be con#rolled by various methods including providing a mold 52 therefore having a plurality of is upstanding pins for piercing the surface during molding or subsequently piercing the surface by needles, laser treatrner~t, chemical treatment; etc:, resulting in surface porosity ranging from impervious to porous, and thereby det$cmining fluid permeability. With regard to fabrira~ng a scaffold 20 for repairing articular cartilage; the scaffold 20 may have three zones, viz.; a porous polymeric phase ac 22 which lies adjacent to cartilage tissue, a porous veran~ic phase 24 virhidy lies adjacent to bone tissue, and an interphase region 26: The ,polymer phase 22 would have an upper urface (skin), which may be provided with a porosity; eg., 75 to 150 ,am to enable he passage of cells. to promote in growth: For articular cartilage, the polymer phase 2Z arid ceramic phase 24 in conjunction with the as fixation component 30, will need to support mechanical loading and thereby protect he invading cells until hey have differentiated and consolidated into tissue that is capable of supporting .a load. The. polymer phase 22 may have a porosity of about 80 to about 95 ;percent with pores thaf are of the order of jam (about 80 pm to about 120 um). It is expected that chor~dtocytes will invade o this zone. The ceramic phase 24 may hwe. larc,~er pores tabout 250pm to about 400 ~mj and a porosity in the range of about 50 to about 95 penrent which is strucfurally compatible with canceilous bone. The interphase region 26 resembles the structural transition between cartitage and. bone.
Several patents have proposed systerrt~ for repairing cartilage that could be used with porous scaffolds of the present invention. For example, U.S.
Patent No. 5,769;899 describes a device for repairing cartilage dafiects and U.S.
Patent No: 5,713;374; describes securing cartilage repair devices with bone s anchors (both hereby incorporated herein by reference) The mpiant 10 described herein may be used for rneniscal repair and regeneration, exhibiting biocompatibility, resistance to crumbling: at the time of surgery, sufficient resistance to compression to allow cell: invasion under load;
and high porosity: The implant is easily sterilized, remodeled by invading tissue, and degrades as new #lssue is being; formed. Furthermore, the scaffold component 20 may be s~c~rrely faed to the site of injury via the fixation component 30.
The implant 10 may have bi-tci-, or multi-layered scaffolds 20.
These layers may be spaced at regular or in~gular interwais and the polymeric I5 phases may be reinforced wi#h a number of reinfiorcements, with the fixation component 30 residing at any desired level within the scaffold 20. The relnfosoements may be In fabric, truss, or particulate form and may be placed at different heights; angles, conformations or gradients in the foam: Both the polymer 22 and ceramic 24 pfiases may. have different porosities depending on zo the applica#ion and may have open cell or doses! c:eli 'structures.
The implant 10 may be affixed to the tissue to be repaired by inserting the post 34 into a sulfaply sized hole in the tissue, e.g:, bone. A
fixative such as calcium phosphate or calcium sulfate cements, PMMA, fibrin glue, adhesives (i.e. cyanoacrylates, butyl acrytates, etc.) may also be used to secure zs the implant 10. .
The following example: is illustrative of the principles and practice of this invention, although not limited thereto. Numerous additional embodiments.
within the scope and spirit of the invention will become apparent to those skilled in the art.
FOR THE REPAIR AND REGENE1~ATION OF TISSUE
Field of the invention The present :invention re~#es generally to the field of tissue mpair and more particularly o composite caffold implants and scaffold fixation devices with post type anchors received in a hole formed in underlying tissue.
Background of the Invention Porous ceramic materials uch as hydroxyapatite, soluble glasses and ceramic forms have been used as scaffolds for the-ingrowth of tissue due to compositional and morphological biocompatabi!'rty. For example, the porosity of is such materials promotes cell 'infiltration.: A variety of methods are used to prepare porous ceramic scaffolds (prostheses);; uch as hydrotherrrtally treating animal bone or coral, burning off polymer beads mixed into a ceramic body, vapor deposition on fioarn, in~itratitm of polymer foam with a ceramic slip and foaming a ceramic slip.
ao One limitation exhibited by porous ceramic materials is their inherent britgeness. Attempts to address this limitation have included back=Riling a ceramic foam with monomer solutions of PMMA or PLA, draining excess solution from the ceramic foam there polymerizing through curing and/or drying in order to impart some toughness to he ceramic foam. Others have proposed 25 laminating oiid or porous polycraeric layers o a ceramic foam structure.
independent from: proposed: uses' in combination with ceramics, polymeric foams. have utility - in the repair and regeneration of tissue. For example, amorphous; polymeric foam has been used to fill voids in bone.
Various rnethods have been explored for preparing the poiyme~ foams; using;
so e.g.. leachabies; vacuum foamirn, g techniques; precipitated polymer gel masses;
and polymer melts with fugitive compounds that sublime at temperatures greater than room temperature. The ~fom~atfon of biocompatible: absorbable foams by lyoph'rlization is discussed in a copending patent application entitled 'Porous Lt ' ' Tissue Scaffoldings for the Repaid and Regeneration of Tissue", assigned to Ethicon, Inc.; docket number 091345096, flied June 30, 1999, hereby incorporated byreference.
Hinsch et al: (EPQ274898)- describes a porous open oeli foam of s potyhydroxy acids for the in. grovi~th of blood ~essets and cells. The foam can be reinforced with fibers, yams; braids, knitted fabrics;: scrims and he like.
Athanasiou et al. (U~S: Patent No. 5,607;474) have proposed using a two-layer polymeric foam device for n:pairing osteochondraP defects at a location where two dissimilar types of tissue are present. The two polymeric lo , layers are prepared separately, arid joined together at a subsequent step. Each of the layers is designed to have stiffness and cornpressibitity values that correspond respectively to cartilage and bone tissue, mimicking the cartilagelbone interface. However, the Athanasiou device exhibits an abrupt change in properties from one hyer to the next, whereas the juncture of cartilage i5 and bone displays a gradual transition; with cartilage: cells gradually ganging welt morphology and orientation depending on the location relative to the underlying bone structure: f=urther; collagen fiber orientation within the matrix also d~anges relative ~ its location: in the structure.
H. Levene et al., U.S: Patent No. 6;103,255 describes a process zo used for making a scaffold having a ubstantuaily continuous polymer phase with a distribution of laroge and small pore sizes; with the small pores contained in the walls of the large pores.
tn a study done by G. Niederauer et al. and reported in Biomaterials 21 (2000) 2561; scaffolds for articular cartilage repair were as prepared from layers of polylacticlpalyglycolic acid (PLG) and polylacticJpoiyglycoiic aad reinforced with fibers of the same material, bioglass or calcium sulfate: The PLG layer was made porous in all cases by expanding a precipitated ge! mass of polymer under vacuum at elevated. emperatures. The reinforced layers were made porous in a similar fashion after incorporating the reinforcement. in the polymer solution and prior to precipitation of the polymeric get mass. Once the two layers were fabricated, they were adjoined using a srrtali amount of sowent to glue the two layers together:
t x The use of a porous polymer for the purpose of engineering cartilage is described in the patent by T. Mahood et ai., (EP1027897A1 ) which discloses a mufti-layer polymer scaffold in which the layers are attad~ed by sucxessive dip coating or by the attachment of the two layers to a third. The s third layer is described as a barrier to cell-diffusion, thus co(ifining chondrocytes to the polymer layer and osteobiasts, to the ceramic layer.
Krekiau et al. in 8iomatecials 20 (1999) 1743 have evaluated a fibrous polymeric fleece attached to a porous ceramic material, for the purpose of culturing chondrocytes in the polymeric caffold while simultaneously ?o providing a bone formation inducing absorbable material to simulate articular cartilage. In this study, a fibrin-.cell-solution was used to affix the :ceramic and polymeric: layers by way of encapsula#~ with the intent that.the phases would interact in vitro in order to create a ,mechanically stressabie junction. The authors discuss the possibility of providing: the surfaces of the layers with teeth to increase shear strength. However; there is no mechanism by which the two dlffererat layers are interlocked #c resist delaminating forces in directions perpendicular to the laminate function and there is an abrupt transition beiween the two ,layers. .
In addition to the limitations of the prior art relative to the composition and morphology of tissue scaffolds, the fixadon of the scaffold at the site of injury remains challenging: Various fixatiota methods have been explored, including press-fitting the scaffold into the defect (which may result in slippage or destrudaon of the implanted scaffold) or suturing the scaffold to the periosteai flaps. The tatter approach is not always ideal because the geometry of the as scaffold may not match that of the periosteal flaps or the flaps may have been destroyed or cannot be located:
.It would therefore be advantageous to overcome the above mentioned limitations with a scalffold that provides secure attachment to a defect site.
Summarv.of the Invention The limitations: of the prior art are solved by the present invention which includes a-prosthetic implant having a tissue caffoid and a.fixation device s with a scaffold support and an anchoring post: The anchoring post extends from a surface of the scaffold support at a selected angle with the scaffold support embedded within the scaffold.
Brief Description of FiQUres Figure 1 is a top perspective ~riew of an implant in accordance with an exemplary embodiment of the present invention.
Figure 2 is a aottom perspective view of the implant of Figure 1.
~s Figure 3 is a cross-sectional view of the implant of Figures 1 and 2.
Figure 4 is a cross-sectional view liic$ Figure 3 of an alternative embodiment of the present inventiocy:
2o Figure 5 is a diagrammatic cross sactionai view of the implant of Figure 4 within a rnofd for fabrica~ng-,the mplant.
Detailed Description of the Invention This invention includes an impiantable device with ~ a scaffold as component and a frxation component for mechanically holding the scaffold component in position relative vto a tissue defect to be repaired. The scaffold component is formed around a scaffold support platfomn of the fi~cation component and has a porous biocompatible polymer layer attached to a porous ceramic layer via a porous transitional interface: The scaffolds are particularly s o useful in the repeirlfegeneration of defects present at a, junctiory of tissue types . exhibiting a transitional or gradient morphoiogylphysiology such as at the cartilagelbone junction: The present invention can be utilized to a repairlregenerate a issue junction-by inducing one cell type to proliferate in the polymer phase of the scaffold and a second ceN type to grow in the ceramic phase of the scaffold. Examples of such junction regeneration sites are (a) spinal disc (nuclear and annular cells cultured on tire polymer, phase aid s osteoblasts cultured in the ceramic phase; (b) articuiar or meniscal cartilage (chondrocytes or fibrochondrocytes, respectively, cultured on the polymer phase and osteoblasts cultured in the :ceramic): The present invention may also be utilized to repair the meniscus,. fibrocattilage, tendons, and ligament. The features of the porous polymer phase can be controlled to suit a desired application by choosing the aQpropriate ~ conditions during the process of lyophilization, or freeze drying. The porous polymer foam can be directly lyophilized into the ceramic fracture creating a multiphasic material composed of a polymer foam with or inithout reinforcement structures, an interphase zone of polymer foam diffused within end interlodcingwith theporous ceramic, and the porous ceramic. A portion of the° l3xation component may be placed between the polymer and oerarr~ic layers, which are structurally integrated to resist detachment of the scaffold component. from the fixation component and/or delamination of the composije scaffold under in uivo conditions. The implant may be partially or completely absorbable:
The interphase zone exhibits a micxoporous polymer foam located within the macn~pores of a poFOUS ceramic. The interpenetcation of the two porous layers creates a strong mechanical junction while simultaneously pcovidinga gradual change in material properties for the purpose of regenerating different tissues or oo-culturing different types of cells in inmate contact with one another. The interconnecting pores and channels facilitate the transport of nutrients and/or invasion of cells into the scaffold; facilitating the ingrowth of tissue and more closely mimicking naturally ' ocxufring (issue junctions. The present. invention therefore faci~tates ~ltutar organization and the regeneration of tissue junctions with normal morphology and physiology. The composition 3o and features of the scaffold 20 are deibed in a copending Application fled , contemporaneously herewith, enfitied; "Porous CeramiclPorous Polymer Layered Scaffolds for the Repair and Regeneration of Tissue, (Serial No. to be v , assigned) and assigned to the present assignee; such application being incorporated by reference herein.
The: features of: a scaffold irt accordance with. the present invention can be tailored to suit a particular applica#ion by selecting the appropriate s ceramic, polymer and conditions for iyophifization of the polyriaer to obtain one or more of the following properties: (1 ) inferconnec~ng polymer foams attached to the porous ceramic (2) a variety of poros~ties ranging from about 20% to about 98°~ for the :polymer foam; (3) a gradient in the pore size between the polymer and ceramic-, (4) channels that nm through the porous polymer foam for improved cell invasion, vascularization and nutrient diffusion; and (5) micro-patteming of pores or the addition of other polymer structures on the surface of the polymer for cellular organization or to limit cellular invasion.
in addition, ttie scalffotd can include (1 ) porous ~mposifies with a composition gradient to elicit or, tatce advantage of. different cell response to ~s different materials; (2) reinforcement with knitted; braid; woven; or non-woven fabrics or' meshes; or truss strt~cterres in ordef to impart desired mechanical properties; (3) blends of different polymer compositions to create a potymer phase that has portions that <will break down at different rates; (4) multi-layer composite structures with layers of ;alternating porous ceramics and polymers;
Zo (5) a polymer phase co-lyophilized or coated with pharmaceutically active compounds; (6) a ceramic phase coated with pharmaceutically active compounds such as growth factors and/or (7) cells which may be cultured prior to or at the time of implantation. .
Referring to Figures 1 through 4, the implant 10 includes a scaffold is component 20 and a fixation component 30 (See Figure 3). Scaffold component 2t3 has ;polymeric phase Z2 arid ceramic phase 24; which are mechanically interlocked at interphase region 26: Polymeric phase 22, ceramic phase 24, and interphase n3gion 26 preferably have pores 23, 25, 27,' respectively, with an open cell structure. As shown in Figure 3; fixation component 3D includes scaffold support 32 and anchoring post 34. Though not shown in the figures;
anchoring post 34 may feature' ribs, aerrations; or other surtace roughness or engagement features that improve the attachment of anchoring post 34' to the implant site; e.g., a hole in bone tissue. A preferred f~cation component for use ~ 02391697 2002-06-26 in the present invention is described in U.S: Patent Application Seria( No.
091793,029; entitled, "Scaffold Fiacation Device For Use In Articular Cartilage Repair", filed on 2126L01, assigned o the preserit assignee and which is hereby incorporated herein by reference.
s . The implant 10 must have structural integrity to facilitate ease of handling iy an operating room environment, i.e.scaffold component 20 and fixation compon~nt 30 must not separate before, during; or after the surgical procedure. Adequate strength and: :physical properties ale developed in the-implant through the selection of materials used to form the scaffold 20 and fixation 3Q components, and fihe manufacturing process.
As shown in Figures 3 and 4, the scaffold component 20 fully .
encapsulates scaffold support 32 -of the frxation component 30. This encapsulation serues as ttie means of attaching the scaffold component 20 to the fixation component 30: Figure 3 shows scaffold support 32-of the fncation i5 component 30 embedded in the polymeric phase 22 with the lower surface 31 abutting the interphase region 26. to a preferred embodiment shown in Figure 4, scaffold support 32 of the fixation component 30 is fully encapsulated in all three components 22! 24; 26 of scaffold component 20. This is achieved by fully or partially countersinking scaffold support 32 in ceramic phase 24.
zo The infusion of the polymeric phase'22 into the ceramic phase24 securely fastens the finro phases 22;=24 and supports the brittle structure of the porous ceramic phase 24. The polymer 22 acts as a cushion to dissipate impact energy to shield the brittle ceramic 24 from ca#astrophically damaging Stresses:
In addition; the communicating . pores 23; 25, 2? encourage the growth of zs different types of Ails, promoting the regeneration of different adjoining layers of .
tissue at an injured tissue junction.
.The pores 25 in the ceramic phase 24 are interconnected, and may be selected to have pore sizes ranging from 25 to 600 microns, preferably from 100 to 250 microns. The pores 23 in the polymeric phase 22 are also s o interconnected and range in size from about 10 to 250 microns, preferably 30 to 150 microns. The temps "micropore" and "macropore":may be used to designate the tH/O $iZe Scales Of pOre$ 23; 25 found in the scaffold 10. If the bridle ceramic phase 24 is cracked, the polymeric phase 22 in the ihterphase region 2s holds f ' the caffold component 20 together. The composite scaffold component 20 facilitates the creation of a strong bond between different types of tissue such as in the repair and regeneration of articular cartilage, meniscus, and spinal discs.
The embedding of fixation component 30 within he scaffold s component20 minimizes their combined hickness minimizing the depth of the hole in the tissue made to receive the implant 10 and the assvaated damage o the tissue proximate to the defect. In addition, ceramic phase 24 of scaffold component 20 (in conjunction with the polymeric phase 22j provides support to the hard tissue surrounding the implant, minimizing the likelihood of the collapse io , of hard tissue in the region of implant device 10; as well as facilitating the regeneration of minerali2ed hard tissue (bone).
The implant device 10 may be' fabricated by feeding anchoring post 34 of fixation component -30 through a hole in ceramic phase 28 . such that scaffold support 32 rests on top of, or in a countersunk region of, ceramic phase ~s 24. This assembly is then partially introduced into a polymer solvent system allowing he polymer-solvent system to infiltrate into he porous ceramic phase.
The polymer phase 22 is then foamed: The desired polymers may be foamed by lyophiiization, supercritical solvent foaming. (i.e., as: described in EP
4fi416381 ), gas injection extrusion; gas injection molding or casting with an extractable zo material (i.e., salts, sugar or any other means known to dose skilled in the art):
It should be appreciated that the scaffold support 32yrnay have openings therein through which the polymer 22 mar contact fhe ceramic 14 it is preferred to foam the polymer :22 by lyophilization, or freeze drying: Suitable methods for lyophilizing elastomeric polymers to form foams is 2s described in the following examRie and in: the peeing U:S: patent applications entitled, "Process for Manufacturing Biomedical Foams°, Serial No;
09/345095, flied June 30, 1999 and 'Pcirous Tissue Scaffoldings for the Repair or Regeneration of Tissue"; Serial No091345098; filed June 30,1999, both assigned to Ethicon, Inc. and hereby incorporated, herein by reference.
30 Figure 5 illustrates a molding apparatus 50 having mold 52 and support bracket 54. Support bracket 54 includes a hrougfi note 53 which is aligned over the well 55 of motdr52. A hotder 40; having :head 42 and pin 44, may be used to hold fixation component 30: Pin 44 passes through hole 53 with head 42 abutting support bracket 54. Pin 44 inserts into bore 46, holding fixation components 30 over the welt 55 penclt~tousty; by a fricfion fit:
Palymes-solvent,syetem 28 is infused into the vNeN 55 ofimoid 52, .to a level such that polymer solvent system 28 contacts veramic phase 24.
s Polymer solvent system 28 is of love viscosity and wicks via capillary action into ceramic phase pores 25. Other methods of infiltrating include, but are not limited to, injecting the polymer-soiventaystem into the ceramic 24 under pressure and vacuum assisted inftltration. - The orientation of 5xation component 30 within the polymer-solvent system 28 determines the orientation of the fixation component 30 within imptanf 10: Although the: means of aligning fixation component 30 in the welt 55 of mold 52 include support bracket 54 anti a fricfion fit between connector pin 44 of holder 40: and fixation component 30, other means to accomplish the same objective ;should be readily apparent to one skilled in the art. The mold 52 can be made from any material that does not chemically react ~s with the polymer-solvent system 28 and is preferably formed from a heat conductive material.
The molding apparatus 50 is ptaced in a lyophilizer (freeze :dryer).
to undergo directional cooling through the wall of mold 52 that is in contact with the lyophilizes shelf, which is subjected to a thermal cyde. The heat transfer ac front moves upwards from: the lyophilizes shelf through the mold wall into the polymer solvent system 28. lAilhen the temperature of the polymer solution goes below the gelation andlor freezing point, 1t separates into polymer and solvent phases giving rise to the ceillfoam structure:
The pore morphology that ~ results from the freezing step is a is function of solution thermodynamics, freezing rate, temperature to~ which it is ~oied:; concentration of the solution, the presence of reinforcement elements, the presence of an adjoining layer, he . occurrence of t~mogeneous or heterogeneous nucleation etc. Detailed descriptions of these phase separation phenomena are known In the art and can ' be found in the references "Microcellular foams via phase eparation" by A: T. Young, J. Vac: Sri.
Technol., A 4(3),'Mayl;Jun 1986; and "Th~errnodynamics of Formation of Porous Polymeric Membrane from Solutions" by S'. Matsuda, Polymer J. 23(5), (1:991 ) 435. The lyophiiization process can therefore be used to bond the polymer and ceramic layers 22; 24 while simultaneously creating a composite material with the correct pore structure to regenerate- tissue.
The porous ceramic phase 24 of the scaffold may be composed of mono-, di-; tri-, a-tci, a-tri, and tetra-calaum phosphate, hydroxyapatite, fluoroapatites; calcium sulfates, catdum fluorides; ~Iautr~ oxides, calaum carbonates; magnesium calcium phs~sphates, bioglasses; and mixtuies thereof.
There are a number of suitable porous biocorypatible ceramic materiats currently available on the commercial market uch as Surgibone (Unilab Surgibone; Inc., Canada), Endobon (Merck Biornaterial France, France); Ceros (Mathys, A. G., io . Bettiach; Switzerlandj, and interpore (interpose, Irvine: CA, United States):
Alternatively, the ceramic phase 14 may be in the form of a porous polymer matrix with indusions of short ceramic fibers or particutates. This alternative ceramic phase 14 ray be formed: by vonventional methods fior working plastics, such as injection molding; with the porosity ther~f provided by is teachable inclusions, molds with pore forming pins, or drilling.
The polymeric phase 22 may be either a natural or synthetic polymer, or combinations of both: Natural biopotymers include collagen;
elastin, alginate, chitin, hyaluronic acid, and others. Examples of suitable synthetic biocompatible, bioabsoFbable polymers that oouki be used include aliphatic ao polyesters, poiy(araino aads), copoly(ether-esters); polyalkylene oxalates, polyamides; poly(iminocarbonates), polyorthoesters, potyoxaesters, polyamidoesters, polyoxaesters containing amine groups; pofy(anhydrides), polyphosphazenes, biomotecules; and blends thereof.
For the purpose of this- inverytion aliphatic polyesters include but 25 are not limited to homopolymers and copolymers of testicle (which includes lactic acid, D-;L- and meso testicle), gtycolide (including glycolic acid), E-caprolachone, p-dioxanone (1,4-dioxan-2-one); trirnethylene carbonate (1,3-ciioxan-2-one);
alkyl derivatives of trimethyiene cafbonate, &vaterolacton~e~ ~-butyroiacto~ne, butyrolactone, ~-decalactone, fiydroxybutyrate, hydroxyvalerate, 1,4-dio~cepan-30 one (including its dimer 1,5;8,12,tetraoxacyciotetradecane-?,14-dione), 1;5-dioxepan-2-one, 6,6-dimethyt-1,4-dio~can-2-one; 2,5-diketomorpholine;
pivalolactone, alpha, alpha-diethyipropiolactone, ethylene carbonate; ethylene oxalate, 3-methyl-1,4-dioxane:2,~-dione: 3,3-diethyl-1,4-dio~can-2;5-dlone, 68-dioxabicydoctane-7-one and polymer blends thereof:
Poly(iminocarbonates) for the purpose of this invention include those desrcxibed by Kemr~itzet and Kohn, in the Handbook of Biadearadable s Polymers; . edited by Domb; . Kost and Wisemen, Hardwooii Academic Press, 1997; pages 251-272. Copoiy(ether-esters) fvr fhe purpose of this invention include those oopoiyester-ethers described by Cohn and Younes J. Biomater:
Res., 22, :(198$) 993, and Cahrt; Polymer Preprirris, 30(1), (1989) 498. .
Polyalkylene oxalates for the pWrpose of this invent~n include ~o , those described in U.S. Patent Nos: 4,208,511; 4,141,087; 4;130,639;
4,140,678; 4;105;034; and 4,205,399-(incorporated by reference herein).
Potyphosphazenes for the purpose of his invention include cc-, ter- anti higher order mixed monomer basal polymers rriade from L-tactile; D,L-lactide, lactic acid, giycolide, glycoiicv acid; para-dioxanone, trirnethytene carbonate and s-caprofactone those described by Allcock in The Encuctopedia of Polymer Science, ~ley lntersciences, John Wiley & Sons, 13 (1988) 31, and by Vandorpe, Schacht, Dejardin and .Lenvnouchi in the Handbook of Biodecaradable PWy-mess; edited by Domb, Kost and WisemerrHardwood Academic Press, (1997) 161 (which are hereby incx~rporated by reference herein).
ac Polyanhydrides for the purpose of this invention indude those from diacids of the form H40C-C6H4-O-(CH~~"-O-CBH4-COOH where m is an integer in the range of from 2 to 8 and copolymers thereof with aliphatic alpha-omega . diacids of up to 12 carbons.
Poiyoxaesters, polyoxaamides and polyoxaestets containing as amines andtor arr~ino groups for the purpose of this' invention include those described in one or more of the failowing U:S. Patent Nos. 5;464,929;
5,595;751;
5;597,579; 5;607,fi87; 5,618;552; 5,620,698; 5;645,850; 5,648,088; 5698,213;
5,700,583;: and 5;859,150 (which are incorporated herein by reference).
Polyorthoesters for the purpose of this invention include those described by Helier in the Handbook of Biodegradable Polymers, edited by Domb, Kost and Wisemen; Hardwood Academic Press, (1997), 99 (hereby incorporated herein by reference).
Aliphatic polyesters are preferred for making he polymer phase 22:
Aliphatic polyesters can be Momopoiymers; copolymers (random, block, segmented, tapered blocks, graft,; triblodcetc.) having a linear, branched or star structure: The preferred morphology ofi the: copolymer chains is linear:
Suitable s monomers: for making aliphatic hornQpolymers and copolymers may be selected from the group consisting of, but not limited to, lactic acid; lactide (including L-, D-, meso and D;L mixtures), giycolic acid, glycolide, E-caprolactone, p-dioxanone (1,4-dioxan-2-one), trimethyier~e carbonate. (1;3-dioxan-2-one), delta-valerolactone, beta-butyrolactona, epsilon-decalactone, 2,6-diketomorphoiine, pivalolactone, alpha, alpha-diethylpropiolactone, ethylene carbonate, ethylene oxalate, 3-methyl-1,4-dioxane-2,5-dione, 33-diethyl-1;4-dioxan-2;5-dione, gamma-butyrolactone, 1;4-dioxepan-2=one, 1,5-dioxepan-2-one; 6,6-dimethyl-dioxepan-2-one, 6,8-dioxabicyclo~tane-7-one and combinations thereof.
Etastomeric cop~lyrjtiers also are particu(ariy useful in the present ~s invention. Suitable bioabsorbable, biocompatible elastomers include, but are not limited to, those selected from the group consisting of eiastomeric copolymers of s-caprolactone and glycolide (preferably having a mole ratio of e-caprolactone o glycolide of from about. 35:65 .to about fi5:35, more preferably from 45:55 to 35:65); eiastomeric copolymers of ~-caprolactone and lactide; -including L-lactide, D-lactide blends thereof oc tactic acid copolymers (preferably having a mole ratio of s-caprolackone to lactide of from about 35:65 ~ to about 65:35 and more preferably from 45:55 to 30:70 or from about 95:5 to about 85:15); elastomeric copolymers of p-dioxanone (1,4-dioxan-2-one) and Iactide including L-lactide;
D
lactide and lactic-aad (preferably having a mole ratio of p-dioxanone to lactide of is from about 40:60 o about 60:40); elastameric copolymen,:of E~proiactone and p-dioxanone (preferably having a: mole ratio of ~-caprolactone to ;p-dioxanone of from about from 30:70 to about 90:30); elastomeric copolymers of p-dioxanone and trimethylene carbonate (preferably having a mote ratio of p-dioxanone to trimethylene carbonate of fnam about 30:10 to about T0:30); eiastomeric ao ~poiymers of trimethylene carbonate and giycolide (preferably having a mole ratio of trime#hyiene carbonate to giycolide of from about 30:70 to about 70:30), elastornerie copolymer of trimethylene carbonate and lactide including L-lactide, D-lactide, blends thereof or lactic acid copolymers (preferably having a mole ratio of trimethyfene carbonate to lactide of from about 30:70 to abcaut 7U:30);
and blends hereof. Examples of suitable bioabsorbable elastomers are also described in U:S: Patent Nos. 4,045:;18, 4,057;537 and 5,468;253, al( hereby incorporated by reference.
s In the preferred embodiments of his invention, ~ the elastomer from which the foams are formed will exhibit a percent elongation greater than about 200 percent and preferably greater than about 500 percent. The properties that determine the degree of elasticity of'the bioabsarbable etastomer are achieved while maintaining a tensile strength greater than about 500 psi, preferably greater than about 1 X000 psi, and a tear strength of greater than: about 50 Ibsrnch, preferably greater than about 80 Ibsiinch. , The polymer or copolymer suitable for forming the polymer phase 22 for any particular application depends on sevefal factors. The chemical composition, spatial dis#ribution of the phases, 'the molecular weight of the is polymer and ~e degree of crystallinity; all dictate to some >extent the in vitro and in vivo behavior of the poiymec.'However, the selection of the polymer to make foams for tissue regeneration largely d$pends on (but is not limited to) the following factors: (a) ,bioabsorpt'ron (or biodegradation) kinetics; (b) in vivo mechanical- performance; (c) ceN response to the material in terms of cell ao attachment; proliferation, migration and differentiatiort and (d) biocompatibility.
The ability of the polymerphase to resort in a timely fashion in vivo is critical. The differences in the: absorption time under in yivo conditions caa also be the basis for combining two different copolymers: For example, a copolymer of 35:65 s-caprolactorie and vglycolide (a relatively fast absorbing as polymer) is blended with 40:60 e-caprolactone and (L)lactlde copolymer (a relatively low absorbing polymer) to form ' a foam. Such a foam could be processed to yield several different physical structures depending upon the technique used. The two phases can be either: randomly inter-connected bicontinuous phases, or have a gradient or laminate composition with an integrated interface between the phase layers. ' The microstructure of these foams cart be optimized to regenerate or repair the desired anatomical features of the tissuethat is being engineered.
Suitable solvents for the preferred absorbable :aliphatic polyesters that will not affect the ceramic foams include but are got limited to sohrents selected from a group consisting of formic acid, ethyl formats, acetic acid, hexafluoroisopropanol (HF1P);cyc~ic ethers (i.e. THF, DMF; and PDO); acetone;
s acetates of C2 to C5 alcohol (such as ethyl acetate and t-tiutylacetate), gtyme (i.e. monoglyrne; ethyl glyme, diglyme, ethyl diglyme, triglyme, butyl diglyme and tetraglymej methylethyl ketone, dipropyleneglycol methyl ether, lactones (such as ~vaierolac~one; S-valerol~c~one(i-butyrota~one, y: butyrolactone) 1;4 dioxane; 1,3-dioxolane, 1,3-dioxolane 2~ne (ethylene c~rbonatej, dimethlycarbonate; diethytcarbonate; benzene, tc~uene, , benzyl alcohol, p xytene, naphthalene, tetrahydrofuranN-methyl pyrrotidone, dime~ylformamide;
chloroform,; 1,2-dicfiloromethane; morpholine; dirnethylsulfoxide, hexafluoroacetone esquihydrate (HFAS), anisoie and mixtures thereof. Among these solvents; the preferred solvent is 1,4-dioxane. A homogeneous solution of ns the polymer in the solvent is prepared using standard echniques:
Additionally; polymer solvent system 28 can be solidified with various reinforcements such as . films, scrims, woven, nonwoven, knitted or braided textile structures incotporated therein: In addition fio attenng he n~qhanicaf properties of the polymer 22, reinforcements can be utilized: (i) to ao modify the in vitro behavior of the polymer. 22, e.g., by introducing a different in vitro profile; (ii) as a canier for the contfolled release of a dnrg; anti (iii): as a carrier for Micro-Electro Mechanicat ~xsterns (MEt~IS).
Solids may be added to the polymer-solvent system 28 during,the processing -of the implant 10 to. act as buffers, reinforcing materials, porosity as modifiers; andlor radio~paque markers to allow imaging after implantation.
Suitable solids include, but are not limited; to, particles of demineralized bone;
calcium phosphate particles, calaurn cerbanate particles for bone repair;
teachable solids for pore creation and- particles of bioabsorbable polymers not soluble in the solvent system as reinfording agents or fio~ the creation of pores as tney aye absorbed:
Suitable teachable solids include but are not limited to nontoxic teachable materials such as ~sa#ts (ie., sodium ctfiloride, ;potassium chloride, calcium chloride, sodium tartra#e, sodium citrate; and the like).
biocompatible mono and disaccharides (i:e.; glucose, fructose, dextrose, maltose; lactose and sucrose), polysaccharides (i:e:, starch, alginate); water soluble proteins (i.e:, gelatin and agarose) and paraffin: .Generally all of these roateriais ~vitf have an average diameter of fens han about 1 mm and ,preferably will have an average s diameter of from about 50. to about 500: tem. The particles will generally constitute from about 1 to about 50 uolurt~ percent of the total volume of the particle and poiymec safvent mixture (wherein the total volume percent equals 100 volume percent). , .The teachable materials can be reranove~d~ by immersing the foam with the teachable material in a solvent in which the particle is soluble io : for a sufficient amount of time to allow leaching of subs#anfiaity ati of the particles, but which does not dissolve or detrimentally alter the foam. The preferred extraction solvent is water, most preferably distilled-deionized water.
This process is described ~ in tJ:S. Patent No. 5;514;378, hereby incorporated herein by reference: Preferably the foam will be dried-after a leaching process is is complete at low temperature and/or vacuum dried to minimize hydrolysis of the foam unless accelerated absorption of the foam is desired.
Various proteins (including short chain peptides), growth agents, chemotatic agents and therapeutic agents (antibiotics; analgesics; anti-inflammatoties, anti-rejection (e.g.: irnrnunosuppressa~ts) and anticancer dn~gs), zo or ceramic particles can be added to the composite scaffold . 20 during processing Qr adsorbed onto the surface or back-felted into the scaffold 20 after fabrication. The pores 25 of the ceramic phase 24 andlor the pores 23 of the polymer 22 may be partially or completely filled with biocompatible resorbabie synthetic :polymers or polymers (such as~ collagen or elastin} or biocompa#ible 25 ceramic materials (such as hydroxyapatite) and combinations thereof (that may or may not contain :materials that promote tissue' growth). Suitable materials include but are not limited to autograft, atlograft, ar xenograft bone, bone marrow; morphogenic proteins (BMPs); epidermal growth factor (EGF), frbroblast growth facfior (FGF)platelet derived growth factor {PDGF); insulin derived 3o growth factor (!GF-i and lGF-li), transforming growth factors (TGF-p), vascular endothelia growth factor (VEGF), platelet rich plasma (PRP) or other osteoinciuctive or osteoconductive rr~aterials known in the art: The polymer fillers could also be conductive or _chemotactic materials; or delivery vehicles -for growth factors: Examples would be recombinant or animal derived collagen or elastin or hyaturonic acid.
Bioactive coatings or surface treatments could also be applied to the surFace of the implant 10. For example; bioactive peptide sequences s (RGDsj could be applied to faciii~ate protein adsorption acrd subsequent cell tissue attachment.
Therapeutic agents may also be delivered via the implant 10. The polymers and blends that are used to form the scaffold 20 can contain therapeutic agents. Far example, polymer 22 could be mixed with a therapeutic agent prior to forming the composite scaffold 20 or loaded into the scafifold after it is formed: The variety of different therapeutic agents that can be used in conjunction with the implant 10 of the present invention is vast. In general, therapeutic agents which may be administered via ttie implant 90 include; without limitation:
antiinfec~ives such: as ant~iotics and antiviral agents; chemotherapeu#ic agents (i:e:
anticancer agents); anti-rejection agerfts; analgesics ::and analgesic combinations; anti-inflammatory agents; hormones such as steroids; growth factors (bone morphogenic proteins ti.e. BMPs 1-?), bone morphogenic-like: proteins (i.e.
GFD-5, GFD-? and Gf=D-8); epidermal growth factor (EGt=), flbroblast growth factor (i:e. FGF 1-9j; platelet derived growth factor (PDGFj, , insulin; like gfowth factor ao (iGF-! and fGF-il), transforming growth factors (i.e. TGF-~ i-111), .
vascular endothelial growth factor (V~GFjj; and other naturally derived or genetically engineered :proteins, polysaccharides, glycoproteins, ~r iipoptaoteins: These factors are described in The Cellular and Molecular Basis of Bone Formation and Re air by Vicki Rosen and R. Scott Thies, published by R:G. Landes Company a hereby incorporated herein by reference:
Composite scaffolds 20 containing bioactive materials may be formulated by mixing one or more therapeutic agents with the polymer used to make the polymer phase 22, with the solvent,-or with the polymer-solvent mixture that is then foamed via lyophiiization. Alternatively, a therapeutic agent may be o coated on the composite scaffold 20 with a Pharmaceutically acceptable carrier that does not dissolve the scaffold 2Q. The therapeutic agents; may be a liquid, a finely divided solid; or any other appropriate physical form: Typically, but optionally, the matrix will include one or more additives, such as diluents, carriers;
excipients;
stabilizers or he like. The type of pplymer and drug concentration can be varied ~to control the release. profile and the amount of-drug dispensed. Upon contact with body fluids, the drug will be released: if the drug is incorporated into the scaffold 20; then the drug is released as it undergoes gradual degradation (mainly s through hydroiysisj. This can resulk in prolonged -delivery (over, say 1 0 5,000 hours, preferably 2 to 800 hours) of~ effective amounts (say, 0:0001 mglkgfiour to mglkglhourj of the drug:
As outlined in Vacanti, U.S. Patent No. 5,??0,41 ?; cells can be harvested from a patient (before apt during urgery to repair the tissue) and he lo , cells can be processed under sterile conditions to provide a specific cell type (i.e., piuripotent cells, stem cells, ~rnarrow cells, progenitor human autologaus adipose tissue (PHAAT) cells or-precursor veils, such as; the mesenchymal stem cells described in Caplari; U.S: Patdnt No. 5,486;359). These veils, e.g., myocytes, adipocytes, fib~omyoblasts, ectodermal ceU, musvle cells; osteoblast is (i.e: bone cells), chondrocyte ~r:e. carkilage sails); endothelial ce~is, fibroblast, panvreatic veils; hepatocyte, bile duct cells, bone r~aarrow cells; neural veils;
genitourinary cells :(including nephritic cells). and combinations thereof rnay be applied or seeded into the porous composite caffold 20. Autogenous, allogeneic, xenogeneic cells maybe used. The veils may be cultured ex vivo so and then reimplanted. Tissue may be harvested from a patient, processed to select certain veils andlor growth factors, such asPRP (Platelet rich plasma), and then reimplanted with the implant 10 back into the patient. The implanted cells could also contain inserted DNA encoding a protein.that could stimulate the attachment, proliferation or differentiation of tissue.
Cells may be implanted into tip scaffold 20 by placing the scaffold in a veil culture such that the veils invade the micfopores 23. and macropores 25: The scaffold 2~ can then be implanted into the patient. The in vitro seeding of cells could provide for a more rapid development and differentiation process for the tissue. It is clear that cellular differentiation and :tee cxeation of tissue o specific extraceltular matrix is critical for the tissue engineerihg of a functions( implant: !t is known that different cell types (stromai cells and d~ondrocytes) can be cultured on different structures. A gradient stcuctuce also allows fog co-cultured tissue scaffolds 20 to be generated.
One use of the construct described herein is for the repair and regeneration of articular cartilage. A~ticular cartilage is an example of a naturally occurring structure ~nposecl of four different zones that indude the superficial or tangential zone within the first 10 20% of the stn:~ctur~e (this includes Hie s articular surface), the middle.zone, which is 40-GO% of he rniddle structure, the deep zone that is adjacent to the tide mark, :and a transition zone between the bone and cartilage that is composed of caldfceci cartilage: Subchondral bore is located adjacent to the tide mark: and this transitions into cancellous bone:
As described-above, the present invention permits the fabrication of a scaffold, e.g., 20 having multiple layers, each having its ~ own characteristics of composition, porosity, strength; etc, Accordingly; the scaffold, e.g., 20 may act as a ternptate for multiple distinct tissue zones as are present in articular cartilage.
The surface porosity of the polymer phase 22 can be con#rolled by various methods including providing a mold 52 therefore having a plurality of is upstanding pins for piercing the surface during molding or subsequently piercing the surface by needles, laser treatrner~t, chemical treatment; etc:, resulting in surface porosity ranging from impervious to porous, and thereby det$cmining fluid permeability. With regard to fabrira~ng a scaffold 20 for repairing articular cartilage; the scaffold 20 may have three zones, viz.; a porous polymeric phase ac 22 which lies adjacent to cartilage tissue, a porous veran~ic phase 24 virhidy lies adjacent to bone tissue, and an interphase region 26: The ,polymer phase 22 would have an upper urface (skin), which may be provided with a porosity; eg., 75 to 150 ,am to enable he passage of cells. to promote in growth: For articular cartilage, the polymer phase 2Z arid ceramic phase 24 in conjunction with the as fixation component 30, will need to support mechanical loading and thereby protect he invading cells until hey have differentiated and consolidated into tissue that is capable of supporting .a load. The. polymer phase 22 may have a porosity of about 80 to about 95 ;percent with pores thaf are of the order of jam (about 80 pm to about 120 um). It is expected that chor~dtocytes will invade o this zone. The ceramic phase 24 may hwe. larc,~er pores tabout 250pm to about 400 ~mj and a porosity in the range of about 50 to about 95 penrent which is strucfurally compatible with canceilous bone. The interphase region 26 resembles the structural transition between cartitage and. bone.
Several patents have proposed systerrt~ for repairing cartilage that could be used with porous scaffolds of the present invention. For example, U.S.
Patent No. 5,769;899 describes a device for repairing cartilage dafiects and U.S.
Patent No: 5,713;374; describes securing cartilage repair devices with bone s anchors (both hereby incorporated herein by reference) The mpiant 10 described herein may be used for rneniscal repair and regeneration, exhibiting biocompatibility, resistance to crumbling: at the time of surgery, sufficient resistance to compression to allow cell: invasion under load;
and high porosity: The implant is easily sterilized, remodeled by invading tissue, and degrades as new #lssue is being; formed. Furthermore, the scaffold component 20 may be s~c~rrely faed to the site of injury via the fixation component 30.
The implant 10 may have bi-tci-, or multi-layered scaffolds 20.
These layers may be spaced at regular or in~gular interwais and the polymeric I5 phases may be reinforced wi#h a number of reinfiorcements, with the fixation component 30 residing at any desired level within the scaffold 20. The relnfosoements may be In fabric, truss, or particulate form and may be placed at different heights; angles, conformations or gradients in the foam: Both the polymer 22 and ceramic 24 pfiases may. have different porosities depending on zo the applica#ion and may have open cell or doses! c:eli 'structures.
The implant 10 may be affixed to the tissue to be repaired by inserting the post 34 into a sulfaply sized hole in the tissue, e.g:, bone. A
fixative such as calcium phosphate or calcium sulfate cements, PMMA, fibrin glue, adhesives (i.e. cyanoacrylates, butyl acrytates, etc.) may also be used to secure zs the implant 10. .
The following example: is illustrative of the principles and practice of this invention, although not limited thereto. Numerous additional embodiments.
within the scope and spirit of the invention will become apparent to those skilled in the art.
3 o In ttx following example, the abbreviation PCL indicates polymerized s-caprolactone; PGA indicates polymerized glycolide; and PLA
indicates polymerized (L~lactide. Additionally, the percentage in front of the copolymer indicates the respective mole percentage of each phase::
Example 1-This example describes the preparation of a composite scaffold with an integral fixation device. ~ .
s A solution of ~e polymer to be lyophilized into a foam was prepared, composed of a 95/5 weight ratio of 1,4-dioxane to 35!65 PCL/PGA.
The polymer and solvent were placed into a flask which was placed into a water bath and heated to 70°C. The solution was heated and stirred for 5 hours.
Afterwards, the solution was filtered using an extraction thimble (extra coarse porosity, type ASTM 170-220(EC)) and stored in the flask.
A ceramic tablet of porous hydroxyapa~te (CERAbio, Prescott, WI) was fabricated with the following dimensions: 7-mm outer diameter; 2 mm inner diameter and 2 mm thickness.
A bioabsorbabie fixation component was manufactured using an ~s injection molding process. The design of the fixation component used is described in copending U.S. Patent Application Serial No: ~9/793,029 entitled;
"Scaffold Fixation Device For Use in Articular Cartilage Repair", which is incorporated herein by reference. The polymer used to manufacture he fixation ~mponents was a copolymer of 85~o PLA and 15% PGA (85/15 PLA/PGA) zo produced by Purac (Gorinchem; The Netherlands) with an i:V: of 1:79 dUg as measured in chloroform. The injection molder (Niigata NN35M1) had a barrel diameter of 18 mm: The hopper was fitted with a nitrogen purge to keep the polymer dry. The feed, transition and compression zone temperatures were 185°C, 185°C and 191 °C, respectively. The die and mold temperatures were 2s 191 °C and 24°C, respectively: The maximum injection-.speed was 80 mmls.
Under cylinder number two, the maximum injection pressure was 85 Kgf/cm2.
The hold pressure was 70 Kgflcxn2. The total time for injection and hold was 3 seconds and the cooling time at the end of hold cycle was 20 seconds:
The fixation cornponent proposed by the foregoing process was so threaded through he 2 mm hole prefabricated in the ceramic tablet and suspended approximately 1.0 - 1.5 millimeters above the bottom surface of a mold as described in reference to Figure 5:
indicates polymerized (L~lactide. Additionally, the percentage in front of the copolymer indicates the respective mole percentage of each phase::
Example 1-This example describes the preparation of a composite scaffold with an integral fixation device. ~ .
s A solution of ~e polymer to be lyophilized into a foam was prepared, composed of a 95/5 weight ratio of 1,4-dioxane to 35!65 PCL/PGA.
The polymer and solvent were placed into a flask which was placed into a water bath and heated to 70°C. The solution was heated and stirred for 5 hours.
Afterwards, the solution was filtered using an extraction thimble (extra coarse porosity, type ASTM 170-220(EC)) and stored in the flask.
A ceramic tablet of porous hydroxyapa~te (CERAbio, Prescott, WI) was fabricated with the following dimensions: 7-mm outer diameter; 2 mm inner diameter and 2 mm thickness.
A bioabsorbabie fixation component was manufactured using an ~s injection molding process. The design of the fixation component used is described in copending U.S. Patent Application Serial No: ~9/793,029 entitled;
"Scaffold Fixation Device For Use in Articular Cartilage Repair", which is incorporated herein by reference. The polymer used to manufacture he fixation ~mponents was a copolymer of 85~o PLA and 15% PGA (85/15 PLA/PGA) zo produced by Purac (Gorinchem; The Netherlands) with an i:V: of 1:79 dUg as measured in chloroform. The injection molder (Niigata NN35M1) had a barrel diameter of 18 mm: The hopper was fitted with a nitrogen purge to keep the polymer dry. The feed, transition and compression zone temperatures were 185°C, 185°C and 191 °C, respectively. The die and mold temperatures were 2s 191 °C and 24°C, respectively: The maximum injection-.speed was 80 mmls.
Under cylinder number two, the maximum injection pressure was 85 Kgf/cm2.
The hold pressure was 70 Kgflcxn2. The total time for injection and hold was 3 seconds and the cooling time at the end of hold cycle was 20 seconds:
The fixation cornponent proposed by the foregoing process was so threaded through he 2 mm hole prefabricated in the ceramic tablet and suspended approximately 1.0 - 1.5 millimeters above the bottom surface of a mold as described in reference to Figure 5:
Claims (25)
1. A prosthetic implant, comprising:
a tissue scaffold;
a fixation device with a scaffold support and an anchoring post, said anchoring post extending from a surface of said scaffold support at a selected angle, said anchoring post insertable into a receptacle formed in tissue, said scaffold support embedded within said scaffold.
a tissue scaffold;
a fixation device with a scaffold support and an anchoring post, said anchoring post extending from a surface of said scaffold support at a selected angle, said anchoring post insertable into a receptacle formed in tissue, said scaffold support embedded within said scaffold.
2. The implant of Claim 1, wherein said scaffold is a composite of a plurality of different materials disposed generally in layers and conjoined at an interface.
3. The implant of Claim 2, wherein a first material of said plurality of materials is a ceramic having a first plurality of pores and a second of said plurality of materials is a polymer having a second plurality of pores, said polymer attached to said ceramic at an interphase region, said polymer infused at least partially into said first plurality of pores in said interphase region.
4. The implant of Claim 3, wherein a portion of said second plurality of pores communicate at least partially with said first plurality of pores in said interphase region.
5. The implant of Claim 4, wherein said ceramic has a hole therein, said anchoring post extending through said hole, said scaffold support abutting against said ceramic proximate said hole; said scaffold support being larger than said hole, preventing said scaffold support from passing through said hole, said interphase region extending proximate to a periphery of said scaffold support.
6. The implant of Claim 5, wherein said ceramic has a countersunk area disposed about said hole, said scaffold support being at least partially contained within said countersunk area.
7. The implant of Claim 6, wherein said scaffold support has at least one opening extending therethrough, said at least one opening permitting said polymer to extend therethrough.
8. The implant of Claim 3, further including a mechanical reinforcement embedded in sand polymer, said mechanical reinforcement selected from the group consisting of films, scrims, woven textiles, non-woven textiles, knitted textiles, braided textiles and trusses.
9. The implant of Claim 3, further including fillers within said polymer selected from the group consisting of growth factors and therapeutic materials.
10. The implant of Claim 3, further including living cells residing on a surface of said scaffold.
11. The implant of Claim 3, wherein at least one of said polymer and said ceramic is biodegradable.
12. The implant of Claim 3, wherein said ceramic is selected from the group consisting of hydroxyapatite, tricalcium phosphate, tetracalcium phosphate, fluoroapatite, magnesium calcium phosphate, calcium sulfate, calcium fluoride, calcium oxide and calcium carbonate.
13. The implant of Claim 3, wherein said polymer is selected from the group consisting of collagen, elastin, hyaluronic acid, chitin and alginate.
14. The implant of Claim 3, wherein said polymer is selected from the group consisting of aliphatic polyester homopolymers and aliphatic polyester copolymers.
15. The implant of Claim 14, wherein said polymer is selected from the group consisting of lactic acid, lactide mixtures of L-, D-, meso and D,L
lactides, glycolic acid, glycolide, epsilon-caprolactone, p-dioxanone (1,4-dioxan-2-one) and trimethylene carbonate (1,3-dioxan-2-one).
lactides, glycolic acid, glycolide, epsilon-caprolactone, p-dioxanone (1,4-dioxan-2-one) and trimethylene carbonate (1,3-dioxan-2-one).
16. The implant of Claim 3, wherein said polymer is an aliphatic polyester elastomeric copolymer.
17. The implant of Claim 16, wherein said copolymer is formed from epsilon-caprolactone and glycolide in a mole ratio of from about 35:65 to about 55:35.
18. The implant of Claim 16, wherein said copolymer is formed from epsilon-caprolactone and glycolide in a mole ratio of from about 45:55 to about 35:65.
19. The implant of Claim 16, wherein said copolymer is formed from epsilon-caprolactone and lactide selected from the group consisting of L-lactide, D-lactide and lactic acid copolymers in a mole ratio of epsilon-caprolactone to lactide of from about 35:65 to about 65:35.
20. The implant of Claim 16, wherein said copolymer is formed from epsilon-caprolactone and lactide selected from the group consisting of L-lactide, D-lactide and lactic acid copolymers in a mole ratio of epsilon-caprolactone to lactide of from about 45:55 to about 30:70.
21. The implant of Claim 16, wherein said copolymer is formed from epsilon-caprolactone and lactide selected from the group consisting of L-lactide, D-lactide and lactic acid copolymers in a mole ratio of epsilon-caprolactone to lactide of from about 95:5 to about 85:15.
22. A method for making a prosthetic implant having a tissue scaffold and an embedded fixation device with a scaffold support and an anchoring post, comprising the steps of:
a) providing a porous ceramic body with a hole extending therethrough;
b) providing a polymer solution;
c) inserting the anchoring post of the fixation device through the hole in the ceramic body such that the scaffold support contacts the ceramic body forming a first subassembly;
d) placing the support scaffold and the ceramic body of the subassembly in contact with the polymer solution;
e) permitting the polymer solution to at least partially infuse into pores in the ceramic body;
f) foaming the polymer solution to produce a polymer foam, the polymer foam interlocking with the ceramic body where the polymer solution was permitted to infuse into the ceramic body and embedding the scaffold support within the resulting conjoined composite.
a) providing a porous ceramic body with a hole extending therethrough;
b) providing a polymer solution;
c) inserting the anchoring post of the fixation device through the hole in the ceramic body such that the scaffold support contacts the ceramic body forming a first subassembly;
d) placing the support scaffold and the ceramic body of the subassembly in contact with the polymer solution;
e) permitting the polymer solution to at least partially infuse into pores in the ceramic body;
f) foaming the polymer solution to produce a polymer foam, the polymer foam interlocking with the ceramic body where the polymer solution was permitted to infuse into the ceramic body and embedding the scaffold support within the resulting conjoined composite.
23. The method of Claim 22, wherein said step of foaming is by lyophilization.
24. The method of Claim 23, wherein said polymer solution is poured into a mold with a hollow well and an implant support overarching the well, and further comprising the step of suspending the implant from the implant support such that the subassembly is submerged in the polymer solution to a selected level.
25
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US09/893,813 US6626950B2 (en) | 2001-06-28 | 2001-06-28 | Composite scaffold with post anchor for the repair and regeneration of tissue |
US09/893,813 | 2001-06-28 |
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Families Citing this family (293)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
ATE220564T1 (en) | 1997-08-14 | 2002-08-15 | Sulzer Innotec Ag | COMPOSITION AND DEVICE FOR REPAIRING CARTILAGE TISSUE IN VIVO CONSISTING OF NANOCAPSULES WITH OSTEOINDUCTIVE AND/OR CHONDROINDUCTIVE FACTORS |
US6179840B1 (en) | 1999-07-23 | 2001-01-30 | Ethicon, Inc. | Graft fixation device and method |
US20020095157A1 (en) | 1999-07-23 | 2002-07-18 | Bowman Steven M. | Graft fixation device combination |
JP2003516803A (en) * | 1999-12-15 | 2003-05-20 | ズルツァー・オルトペディクス・リミテッド | Device for repairing cartilage defects or cartilage / bone defects in human or animal joints |
US8177841B2 (en) | 2000-05-01 | 2012-05-15 | Arthrosurface Inc. | System and method for joint resurface repair |
US7678151B2 (en) | 2000-05-01 | 2010-03-16 | Ek Steven W | System and method for joint resurface repair |
US6610067B2 (en) * | 2000-05-01 | 2003-08-26 | Arthrosurface, Incorporated | System and method for joint resurface repair |
US7896883B2 (en) * | 2000-05-01 | 2011-03-01 | Arthrosurface, Inc. | Bone resurfacing system and method |
US7163541B2 (en) | 2002-12-03 | 2007-01-16 | Arthrosurface Incorporated | Tibial resurfacing system |
US6520964B2 (en) | 2000-05-01 | 2003-02-18 | Std Manufacturing, Inc. | System and method for joint resurface repair |
CA2365376C (en) | 2000-12-21 | 2006-03-28 | Ethicon, Inc. | Use of reinforced foam implants with enhanced integrity for soft tissue repair and regeneration |
US7597715B2 (en) | 2005-04-21 | 2009-10-06 | Biomet Manufacturing Corp. | Method and apparatus for use of porous implants |
US8123814B2 (en) | 2001-02-23 | 2012-02-28 | Biomet Manufacturing Corp. | Method and appartus for acetabular reconstruction |
US20020120340A1 (en) * | 2001-02-23 | 2002-08-29 | Metzger Robert G. | Knee joint prosthesis |
US20030003127A1 (en) * | 2001-06-27 | 2003-01-02 | Ethicon, Inc. | Porous ceramic/porous polymer layered scaffolds for the repair and regeneration of tissue |
DE60219646T2 (en) * | 2001-09-24 | 2007-12-27 | Millenium Biologix Technologies Inc., Kingston | POROUS CERAMIC COMPOSITE BONE IMPLANTS |
US7371258B2 (en) | 2001-10-26 | 2008-05-13 | St. Jude Medical, Inc. | Valved prosthesis with porous substrate |
PT1455689E (en) * | 2001-10-30 | 2007-05-31 | Eyeborn Proprietary Ltd | Orbital implant |
US6712850B2 (en) * | 2001-11-30 | 2004-03-30 | Ethicon, Inc. | Porous tissue scaffolds for the repair and regeneration of dermal tissue |
US8187326B2 (en) * | 2002-05-22 | 2012-05-29 | Advanced Technologies And Regenerative Medicine, Llc. | Attachment of absorbable tissue scaffolds to fixation devices |
US6989034B2 (en) | 2002-05-31 | 2006-01-24 | Ethicon, Inc. | Attachment of absorbable tissue scaffolds to fixation devices |
US7622562B2 (en) | 2002-06-26 | 2009-11-24 | Zimmer Orthobiologics, Inc. | Rapid isolation of osteoinductive protein mixtures from mammalian bone tissue |
US20040002770A1 (en) * | 2002-06-28 | 2004-01-01 | King Richard S. | Polymer-bioceramic composite for orthopaedic applications and method of manufacture thereof |
JP4353510B2 (en) * | 2002-09-09 | 2009-10-28 | 株式会社カネカ | Tissue regeneration support and method for producing the same |
US7824701B2 (en) | 2002-10-18 | 2010-11-02 | Ethicon, Inc. | Biocompatible scaffold for ligament or tendon repair |
US20040078090A1 (en) | 2002-10-18 | 2004-04-22 | Francois Binette | Biocompatible scaffolds with tissue fragments |
US7901408B2 (en) | 2002-12-03 | 2011-03-08 | Arthrosurface, Inc. | System and method for retrograde procedure |
US6994730B2 (en) | 2003-01-31 | 2006-02-07 | Howmedica Osteonics Corp. | Meniscal and tibial implants |
US8388624B2 (en) | 2003-02-24 | 2013-03-05 | Arthrosurface Incorporated | Trochlear resurfacing system and method |
US8197837B2 (en) | 2003-03-07 | 2012-06-12 | Depuy Mitek, Inc. | Method of preparation of bioabsorbable porous reinforced tissue implants and implants thereof |
US6993406B1 (en) | 2003-04-24 | 2006-01-31 | Sandia Corporation | Method for making a bio-compatible scaffold |
US7067123B2 (en) | 2003-04-29 | 2006-06-27 | Musculoskeletal Transplant Foundation | Glue for cartilage repair |
GB0311221D0 (en) * | 2003-05-15 | 2003-06-18 | Orthogem Ltd | Biomaterial |
US7901457B2 (en) | 2003-05-16 | 2011-03-08 | Musculoskeletal Transplant Foundation | Cartilage allograft plug |
DE60321328D1 (en) * | 2003-06-24 | 2008-07-10 | Robert Mathys Foundation Dr H | Prosthetic device for repairing cartilage |
US8226715B2 (en) | 2003-06-30 | 2012-07-24 | Depuy Mitek, Inc. | Scaffold for connective tissue repair |
US10583220B2 (en) | 2003-08-11 | 2020-03-10 | DePuy Synthes Products, Inc. | Method and apparatus for resurfacing an articular surface |
AU2004293042A1 (en) | 2003-11-20 | 2005-06-09 | Arthrosurface, Inc. | Retrograde delivery of resurfacing devices |
US7951163B2 (en) | 2003-11-20 | 2011-05-31 | Arthrosurface, Inc. | Retrograde excision system and apparatus |
EP1845890A4 (en) | 2003-11-20 | 2010-06-09 | Arthrosurface Inc | System and method for retrograde procedure |
US7316822B2 (en) | 2003-11-26 | 2008-01-08 | Ethicon, Inc. | Conformable tissue repair implant capable of injection delivery |
EP1537839A1 (en) * | 2003-12-02 | 2005-06-08 | Dr. h. c. Robert Mathys Foundation | Prosthetic device for cartilage repair |
US7901461B2 (en) * | 2003-12-05 | 2011-03-08 | Ethicon, Inc. | Viable tissue repair implants and methods of use |
US7666230B2 (en) * | 2003-12-08 | 2010-02-23 | Depuy Products, Inc. | Implant device for cartilage regeneration in load bearing articulation regions |
ES2404682T3 (en) | 2003-12-11 | 2013-05-28 | Isto Technologies Inc. | Particle Cartilage System |
US11395865B2 (en) | 2004-02-09 | 2022-07-26 | DePuy Synthes Products, Inc. | Scaffolds with viable tissue |
US7592431B2 (en) * | 2004-02-26 | 2009-09-22 | Immunovative Therapies, Ltd. | Biodegradable T-cell Activation device |
WO2005081982A2 (en) * | 2004-02-26 | 2005-09-09 | Immunovative Therapies, Ltd. | Methods for preparing t-cells for cell therapy |
WO2005089127A2 (en) * | 2004-03-05 | 2005-09-29 | The Trustees Of Columbia University In The City Of New York | Polymer-ceramic-hydrogel composite scaffold for osteochondral repair |
US7767221B2 (en) * | 2004-03-05 | 2010-08-03 | The Trustees Of Columbia University In The City Of New York | Multi-phased, biodegradable and osteointegrative composite scaffold for biological fixation of musculoskeletal soft tissue to bone |
US8137686B2 (en) | 2004-04-20 | 2012-03-20 | Depuy Mitek, Inc. | Nonwoven tissue scaffold |
US8221780B2 (en) | 2004-04-20 | 2012-07-17 | Depuy Mitek, Inc. | Nonwoven tissue scaffold |
US7803182B2 (en) * | 2004-05-28 | 2010-09-28 | Cordis Corporation | Biodegradable vascular device with buffering agent |
US7785615B2 (en) * | 2004-05-28 | 2010-08-31 | Cordis Corporation | Biodegradable medical implant with encapsulated buffering agent |
JP2008504107A (en) | 2004-06-28 | 2008-02-14 | アースロサーフィス・インコーポレーテッド | Joint surface replacement system |
US8512730B2 (en) * | 2004-07-12 | 2013-08-20 | Isto Technologies, Inc. | Methods of tissue repair and compositions therefor |
US8192759B2 (en) * | 2004-07-12 | 2012-06-05 | Isto Technologies, Inc. | Matrix made of polyester polymers entangled with hyaluronic polymers useful for supporting tissue repair |
DE102004044102B4 (en) * | 2004-09-07 | 2014-07-31 | Technische Universität Dresden | Implant for the treatment of osteochondral defects, and process for its preparation |
US20080140184A1 (en) * | 2004-09-30 | 2008-06-12 | Pellegrino-Gensey J Lee | Scaffold device |
US7837740B2 (en) | 2007-01-24 | 2010-11-23 | Musculoskeletal Transplant Foundation | Two piece cancellous construct for cartilage repair |
US8796015B2 (en) * | 2004-11-09 | 2014-08-05 | Proxy Biomedical Limited | Tissue scaffold |
US7828853B2 (en) | 2004-11-22 | 2010-11-09 | Arthrosurface, Inc. | Articular surface implant and delivery system |
US20060157882A1 (en) * | 2004-12-10 | 2006-07-20 | Simona Percec | Filled ultramicrocellular structures |
US8017395B2 (en) | 2004-12-17 | 2011-09-13 | Lifescan, Inc. | Seeding cells on porous supports |
US20060140915A1 (en) * | 2004-12-28 | 2006-06-29 | Schatz Richard A | Veterinary protocol for cellular regeneration |
US7879275B2 (en) | 2004-12-30 | 2011-02-01 | Depuy Products, Inc. | Orthopaedic bearing and method for making the same |
US7896921B2 (en) | 2004-12-30 | 2011-03-01 | Depuy Products, Inc. | Orthopaedic bearing and method for making the same |
US7883653B2 (en) | 2004-12-30 | 2011-02-08 | Depuy Products, Inc. | Method of making an implantable orthopaedic bearing |
ITMI20050343A1 (en) * | 2005-03-04 | 2006-09-05 | Fin Ceramica Faenza S R L | CARTRIDGE REPLACEMENT AND OSTEOCINDRAL INCLUDING A MULTILAYER STRUCTURE AND ITS USE |
US8266780B2 (en) | 2005-04-21 | 2012-09-18 | Biomet Manufacturing Corp. | Method and apparatus for use of porous implants |
US8021432B2 (en) * | 2005-12-05 | 2011-09-20 | Biomet Manufacturing Corp. | Apparatus for use of porous implants |
US8066778B2 (en) | 2005-04-21 | 2011-11-29 | Biomet Manufacturing Corp. | Porous metal cup with cobalt bearing surface |
US8292967B2 (en) | 2005-04-21 | 2012-10-23 | Biomet Manufacturing Corp. | Method and apparatus for use of porous implants |
US7531190B2 (en) * | 2005-05-25 | 2009-05-12 | Biomet Manufacturing Corp. | Porous ceramic structure containing biologics |
AU2006202209B2 (en) * | 2005-05-27 | 2011-04-14 | Lifescan, Inc. | Amniotic fluid derived cells |
PL1888123T3 (en) * | 2005-06-08 | 2013-06-28 | Janssen Biotech Inc | A cellular therapy for ocular degeneration |
US7815926B2 (en) | 2005-07-11 | 2010-10-19 | Musculoskeletal Transplant Foundation | Implant for articular cartilage repair |
WO2007025290A2 (en) * | 2005-08-26 | 2007-03-01 | Isto Technologies, Inc. | Implants and methods for repair, replacement and treatment of joint disease |
US20070055373A1 (en) * | 2005-09-08 | 2007-03-08 | Zimmer Spine, Inc. | Facet replacement/spacing and flexible spinal stabilization |
EP1926459B1 (en) | 2005-09-19 | 2015-01-07 | Histogenics Corporation | Cell-support matrix having narrowly defined uniformly vertically and non-randomly organized porosity and pore density and a method for preparation thereof |
US20070087033A1 (en) * | 2005-10-14 | 2007-04-19 | Sigg Daniel C | Self-fixating scaffolds |
US20070100460A1 (en) * | 2005-10-27 | 2007-05-03 | Rhodes James M | Orthopaedic implant systems with anti-abrasion studs |
US8216319B2 (en) * | 2005-10-27 | 2012-07-10 | Depuy Products, Inc. | Method of repairing a knee joint |
US20070122448A1 (en) * | 2005-11-28 | 2007-05-31 | Alireza Rezania | Compositions and methods to create a vascularized environment for cellular transplantation |
WO2007067637A2 (en) | 2005-12-07 | 2007-06-14 | Isto Technologies, Inc. | Cartilage repair methods |
CN100446817C (en) * | 2006-02-24 | 2008-12-31 | 东华大学 | Microwave heating process for preparing tissue carrier material of polycaprolactone |
CN100446818C (en) * | 2006-02-24 | 2008-12-31 | 东华大学 | Tissue engineering carrier material of polycaprolactone and its prepn process |
US7941875B1 (en) * | 2006-02-27 | 2011-05-17 | Brown Medical Industries | Trabecular matrix like protectors and method |
WO2007127927A2 (en) | 2006-04-28 | 2007-11-08 | Lifescan, Inc. | Differentiation of human embryonic stem cells |
US8741643B2 (en) * | 2006-04-28 | 2014-06-03 | Lifescan, Inc. | Differentiation of pluripotent stem cells to definitive endoderm lineage |
KR100737167B1 (en) | 2006-06-16 | 2007-07-10 | 한국과학기술연구원 | Method for preparing of a porous osteochondral composite scaffold |
EP1878450A1 (en) * | 2006-07-10 | 2008-01-16 | Ecole Polytechnique Federale De Lausanne (Epfl) | Cellular gradient polymer composites |
US20110213375A1 (en) | 2006-07-17 | 2011-09-01 | Arthrosurface, Inc. | Tibial Resurfacing System and Method |
EP2065017B1 (en) * | 2006-08-22 | 2014-01-01 | Mitsubishi Electric Corporation | Laser processing apparatus |
WO2008045807A2 (en) | 2006-10-09 | 2008-04-17 | Active Implants Corporation | Meniscus prosthetic device |
US8192491B2 (en) | 2006-10-09 | 2012-06-05 | Active Implants Corporation | Meniscus prosthetic device |
US20110282392A1 (en) * | 2006-10-30 | 2011-11-17 | Tissue Regeneration Systems, Inc. | Degradable cage for bone fusion |
WO2008054725A2 (en) * | 2006-10-31 | 2008-05-08 | Surmodics Pharmaceuticals, Inc. | Spheronized polymer particles |
CN100421736C (en) * | 2006-11-01 | 2008-10-01 | 华中科技大学 | A gradient laminated composite supporting frame material based on bionic structures and its preparation method |
NL1032851C2 (en) * | 2006-11-10 | 2008-05-14 | Fondel Finance B V | Kit and method for fixing a prosthesis or part thereof and / or filling bony defects. |
US20100047309A1 (en) * | 2006-12-06 | 2010-02-25 | Lu Helen H | Graft collar and scaffold apparatuses for musculoskeletal tissue engineering and related methods |
US9358029B2 (en) | 2006-12-11 | 2016-06-07 | Arthrosurface Incorporated | Retrograde resection apparatus and method |
EP2097117B1 (en) * | 2006-12-11 | 2013-05-22 | Medizinische Hochschule Hannover | Implant of cross-linked spider silk threads |
US8163549B2 (en) | 2006-12-20 | 2012-04-24 | Zimmer Orthobiologics, Inc. | Method of obtaining viable small tissue particles and use for tissue repair |
US20080154372A1 (en) * | 2006-12-21 | 2008-06-26 | Peckham Steven M | Osteochondral implant using a growth factor concentration gradient for repair of bone and cartilage tissue |
PT2097116E (en) * | 2006-12-22 | 2012-12-06 | Medidom Lab | In situ system for intra-articular chondral and osseous tissue repair |
US8328873B2 (en) | 2007-01-10 | 2012-12-11 | Biomet Manufacturing Corp. | Knee joint prosthesis system and method for implantation |
US8163028B2 (en) | 2007-01-10 | 2012-04-24 | Biomet Manufacturing Corp. | Knee joint prosthesis system and method for implantation |
US8187280B2 (en) | 2007-10-10 | 2012-05-29 | Biomet Manufacturing Corp. | Knee joint prosthesis system and method for implantation |
US8157869B2 (en) | 2007-01-10 | 2012-04-17 | Biomet Manufacturing Corp. | Knee joint prosthesis system and method for implantation |
US8562616B2 (en) | 2007-10-10 | 2013-10-22 | Biomet Manufacturing, Llc | Knee joint prosthesis system and method for implantation |
CN103627671A (en) * | 2007-01-30 | 2014-03-12 | 佐治亚大学研究基金会 | Method for generating endoderm and mesoderm lineages and multipotent migratory cells (MMC), and cell population and use |
EP1964583A1 (en) | 2007-02-09 | 2008-09-03 | Royal College of Surgeons in Ireland | Process for producing a collagen/hydroxyapatite composite scaffold |
US8753391B2 (en) * | 2007-02-12 | 2014-06-17 | The Trustees Of Columbia University In The City Of New York | Fully synthetic implantable multi-phased scaffold |
US7758643B2 (en) * | 2007-02-26 | 2010-07-20 | Biomet Sports Medicine, Llc | Stable cartilage defect repair plug |
US8435551B2 (en) | 2007-03-06 | 2013-05-07 | Musculoskeletal Transplant Foundation | Cancellous construct with support ring for repair of osteochondral defects |
JP2008272453A (en) * | 2007-03-30 | 2008-11-13 | Jms Co Ltd | Process for production of porous body and uses thereof |
US20080255665A1 (en) * | 2007-04-11 | 2008-10-16 | Active Implants Corporation | Anchored prosthetic meniscus device |
CA2684040C (en) | 2007-04-12 | 2016-12-06 | Isto Technologies, Inc. | Method of forming an implant using a mold that mimics the shape of the tissue defect site and implant formed therefrom |
ITTO20070373A1 (en) * | 2007-05-29 | 2008-11-30 | Torino Politecnico | ACETABULAR CUP CERAMIC MONOBLOCK FOR HIP PROSTHESIS. |
US8066770B2 (en) * | 2007-05-31 | 2011-11-29 | Depuy Products, Inc. | Sintered coatings for implantable prostheses |
WO2008157285A1 (en) * | 2007-06-13 | 2008-12-24 | Fmc Corporation | Biopolymer based implantable degradable devices |
CN104250632B (en) | 2007-07-01 | 2018-09-11 | 生命扫描有限公司 | Single pluripotent stem cell culture |
US9080145B2 (en) | 2007-07-01 | 2015-07-14 | Lifescan Corporation | Single pluripotent stem cell culture |
EP2014256A1 (en) * | 2007-07-12 | 2009-01-14 | Straumann Holding AG | Composite bone repair material |
US7998380B2 (en) * | 2007-07-13 | 2011-08-16 | Wisconsin Alumni Research Foundation | Method of fabricating a tissue engineering scaffold |
US20090018655A1 (en) * | 2007-07-13 | 2009-01-15 | John Brunelle | Composite Implant for Surgical Repair |
WO2009012428A2 (en) | 2007-07-18 | 2009-01-22 | Lifescan, Inc. | Differentiation of human embryonic stem cells |
WO2009018453A1 (en) * | 2007-07-31 | 2009-02-05 | Lifescan, Inc. | Differentiation of human embryonic stem cells |
US8128703B2 (en) | 2007-09-28 | 2012-03-06 | Depuy Products, Inc. | Fixed-bearing knee prosthesis having interchangeable components |
US8715359B2 (en) * | 2009-10-30 | 2014-05-06 | Depuy (Ireland) | Prosthesis for cemented fixation and method for making the prosthesis |
US8632600B2 (en) | 2007-09-25 | 2014-01-21 | Depuy (Ireland) | Prosthesis with modular extensions |
US9204967B2 (en) | 2007-09-28 | 2015-12-08 | Depuy (Ireland) | Fixed-bearing knee prosthesis having interchangeable components |
CN101878298B (en) * | 2007-11-27 | 2017-08-15 | 生命扫描有限公司 | The differentiation of human embryo stem cell |
US9040072B2 (en) | 2007-12-07 | 2015-05-26 | Ethicon, Inc. | Use of coupling agents to improve the interface in absorbable polymer composites |
JP2011509157A (en) * | 2008-01-09 | 2011-03-24 | イノベイテイブ ヘルス テクノロジーズ エルエルシー | Implant pellets and methods for bone formation and preservation |
JP5232484B2 (en) * | 2008-01-31 | 2013-07-10 | 日本特殊陶業株式会社 | Biological implant |
KR101731474B1 (en) | 2008-02-21 | 2017-05-11 | 얀센 바이오테크 인코포레이티드 | Methods, surface modified plates and compositions for cell attachment, cultivation and detachment |
DE102008010893B3 (en) * | 2008-02-23 | 2009-07-09 | Resorba Wundversorgung Gmbh & Co. Kg | Implant for insertion into an alveolar space |
WO2009111069A1 (en) | 2008-03-05 | 2009-09-11 | Musculoskeletal Transplant Foundation | Cancellous constructs, cartilage particles and combinations of cancellous constructs and cartilage particles |
US8043375B2 (en) | 2008-03-06 | 2011-10-25 | MoiRai Orthopaedic, LLC | Cartilage implants |
FR2928828B1 (en) * | 2008-03-21 | 2010-04-02 | Tornier Sa | CARTILAGE RESURFACING IMPLANT |
US8016884B2 (en) * | 2008-04-09 | 2011-09-13 | Active Implants Corporation | Tensioned meniscus prosthetic devices and associated methods |
US7991599B2 (en) * | 2008-04-09 | 2011-08-02 | Active Implants Corporation | Meniscus prosthetic device selection and implantation methods |
US7611653B1 (en) * | 2008-04-09 | 2009-11-03 | Active Implants Corporation | Manufacturing and material processing for prosthetic devices |
US8361147B2 (en) | 2008-04-09 | 2013-01-29 | Active Implants Corporation | Meniscus prosthetic devices with anti-migration features |
US8623648B2 (en) | 2008-04-24 | 2014-01-07 | Janssen Biotech, Inc. | Treatment of pluripotent cells |
KR101829310B1 (en) | 2008-06-30 | 2018-02-14 | 얀센 바이오테크 인코포레이티드 | Differentiation of pluripotent stem cells |
US8012217B2 (en) * | 2008-07-03 | 2011-09-06 | Fellowship of Orthopaedic Researchers, LLC | Talar implants and methods of use |
CA2729917C (en) * | 2008-07-06 | 2016-09-13 | The Curators Of The University Of Missouri | Osteochondral implants, arthroplasty methods, devices, and systems |
AU2009274517B2 (en) | 2008-07-25 | 2015-03-26 | The University Of Georgia Research Foundation, Inc. | Compositions for Mesoderm derived ISL1+ Multipotent cells (IMPs), epicardial progenitor cells (EPCs) and multipotent CXCR4+CD56+ cells (C56Cs) and methods of use |
US20110305672A1 (en) | 2008-07-25 | 2011-12-15 | University Of Georgia Research Foundation, Inc. | COMPOSITIONS FOR MESODERM DERIVED ISL1+ MULTIPOTENT CELLS (IMPs), EPICARDIAL PROGENITOR CELLS (EPCs) AND MULTIPOTENT CD56C CELLS (C56Cs) AND METHODS OF PRODUCING AND USING SAME |
US20100028307A1 (en) * | 2008-07-31 | 2010-02-04 | O'neil John J | Pluripotent stem cell differentiation |
US10842645B2 (en) | 2008-08-13 | 2020-11-24 | Smed-Ta/Td, Llc | Orthopaedic implant with porous structural member |
WO2010019807A1 (en) * | 2008-08-13 | 2010-02-18 | Smed-Ta/Td, Llc | Orthopaedic implant with spatially varying porosity |
US9616205B2 (en) | 2008-08-13 | 2017-04-11 | Smed-Ta/Td, Llc | Drug delivery implants |
US20100042213A1 (en) | 2008-08-13 | 2010-02-18 | Nebosky Paul S | Drug delivery implants |
JP5774989B2 (en) | 2008-08-13 | 2015-09-09 | スメド−ティーエイ/ティーディー・エルエルシー | Orthopedic screw |
US9700431B2 (en) | 2008-08-13 | 2017-07-11 | Smed-Ta/Td, Llc | Orthopaedic implant with porous structural member |
EP2341852B1 (en) | 2008-08-29 | 2018-08-15 | SMed-TA/TD, LLC | Orthopaedic implant |
US9387280B2 (en) * | 2008-09-05 | 2016-07-12 | Synovis Orthopedic And Woundcare, Inc. | Device for soft tissue repair or replacement |
ES2634445T3 (en) * | 2008-10-31 | 2017-09-27 | Janssen Biotech, Inc. | Differentiation of human embryonic stem cells with pancreatic endocrine lineage |
MX349178B (en) | 2008-10-31 | 2017-07-17 | Centocor Ortho Biotech Inc | Differentiation of human embryonic stem cells to the pancreatic endocrine lineage. |
JP5719305B2 (en) * | 2008-11-20 | 2015-05-13 | ヤンセン バイオテツク,インコーポレーテツド | Methods and compositions for cell attachment and culture on a planar support |
MX356756B (en) | 2008-11-20 | 2018-06-11 | Centocor Ortho Biotech Inc | Pluripotent stem cell culture on micro-carriers. |
US20100151114A1 (en) * | 2008-12-17 | 2010-06-17 | Zimmer, Inc. | In-line treatment of yarn prior to creating a fabric |
US8822610B2 (en) | 2008-12-22 | 2014-09-02 | ATRP Solutions, Inc. | Control over controlled radical polymerization processes |
US8815971B2 (en) | 2008-12-22 | 2014-08-26 | ATRP Solutions, Inc. | Control over controlled radical polymerization processes |
EP2389204B1 (en) | 2009-01-23 | 2019-07-03 | Royal College of Surgeons in Ireland | Layered scaffold suitable for osteochondral repair |
GB2479514A (en) * | 2009-02-23 | 2011-10-12 | Arthrosurface Inc | Nanorough alloy substrate |
KR101073050B1 (en) * | 2009-03-17 | 2011-10-12 | 주식회사 제네웰 | Method For Preparing Porous Scaffold By Cartilage-bone Complex For Cartilage Regeneration |
US20100249832A1 (en) * | 2009-03-31 | 2010-09-30 | Joshua Stopek | Multizone Implants |
US20100249854A1 (en) * | 2009-03-31 | 2010-09-30 | Thomas Jonathan D | Multizone Implants |
US9592043B2 (en) * | 2009-03-31 | 2017-03-14 | Covidien Lp | Multizone implants |
US8556972B2 (en) * | 2009-04-02 | 2013-10-15 | Sevika Holding AG | Monolithic orthopedic implant with an articular finished surface |
US20100256758A1 (en) * | 2009-04-02 | 2010-10-07 | Synvasive Technology, Inc. | Monolithic orthopedic implant with an articular finished surface |
WO2016154393A1 (en) | 2009-04-17 | 2016-09-29 | Arthrosurface Incorporated | Glenoid repair system and methods of use thereof |
EP2429429B1 (en) | 2009-04-17 | 2018-07-25 | Arthrosurface Incorporated | Glenoid resurfacing system |
WO2010121250A1 (en) | 2009-04-17 | 2010-10-21 | Arthrosurface Incorporated | Glenoid resurfacing system and method |
US8475531B1 (en) * | 2009-04-21 | 2013-07-02 | Scott A. Maxson | Anchored multi-phasic osteochondral construct |
WO2010123574A1 (en) | 2009-04-23 | 2010-10-28 | Atrp Solutions Inc | Star macromolecules for personal and home care |
WO2014036498A2 (en) | 2012-08-30 | 2014-03-06 | ATRP Solutions, Inc. | Dual mechanism thickening agents for hydraulic fracturing fluids |
US8173750B2 (en) | 2009-04-23 | 2012-05-08 | ATRP Solutions, Inc. | Star macromolecules for personal and home care |
US9783628B2 (en) | 2009-04-23 | 2017-10-10 | ATRP Solutions, Inc. | Dual-mechanism thickening agents for hydraulic fracturing fluids |
US9775721B2 (en) | 2009-07-10 | 2017-10-03 | Bio2 Technologies, Inc. | Resorbable interbody device |
CN102470195B (en) | 2009-07-10 | 2014-07-23 | 百傲图科技有限公司 | Devices and methods for tissue engineering |
US20110206828A1 (en) * | 2009-07-10 | 2011-08-25 | Bio2 Technologies, Inc. | Devices and Methods for Tissue Engineering |
EP2453937A2 (en) * | 2009-07-14 | 2012-05-23 | Doctor's Research Group, Inc. | Multi-density polymeric interbody spacer and method for fabrication thereof |
US20110015743A1 (en) * | 2009-07-14 | 2011-01-20 | Doctors Research Group, Inc. | Multi-density polymeric interbody spacer |
RU2540021C2 (en) * | 2009-07-20 | 2015-01-27 | Янссен Байотек, Инк. | Differentiating human embryonic stem cells |
AU2010276438B2 (en) | 2009-07-20 | 2015-06-11 | Janssen Biotech Inc. | Differentiation of human embryonic stem cells |
CN103952372B (en) | 2009-07-20 | 2016-10-05 | 詹森生物科技公司 | The differentiation of human embryo stem cell |
ES2566026T3 (en) | 2009-08-25 | 2016-04-08 | Fellowship Of Orthopaedic Researchers, Inc. | Trochlear implants |
AU2010319921A1 (en) * | 2009-10-29 | 2012-05-17 | Janssen Biotech Inc. | Pluripotent stem cells |
WO2011079018A2 (en) * | 2009-12-23 | 2011-06-30 | Centocor Ortho Biotech Inc. | Differentiation of human embryonic stem cells |
WO2011079017A2 (en) * | 2009-12-23 | 2011-06-30 | Centocor Ortho Biotech Inc. | Differentiation of human embryonic stem cells |
US9011547B2 (en) | 2010-01-21 | 2015-04-21 | Depuy (Ireland) | Knee prosthesis system |
US8444699B2 (en) * | 2010-02-18 | 2013-05-21 | Biomet Manufacturing Corp. | Method and apparatus for augmenting bone defects |
US8974519B2 (en) | 2010-02-19 | 2015-03-10 | Cardiovascular Systems, Inc. | Therapeutic agent delivery system, device and method for localized application of therapeutic substances to a biological conduit |
IT1398443B1 (en) * | 2010-02-26 | 2013-02-22 | Lima Lto S P A Ora Limacorporate Spa | INTEGRATED PROSTHETIC ELEMENT |
CN102791851B (en) | 2010-03-01 | 2017-07-14 | 詹森生物科技公司 | The method of cell of the purifying derived from multipotential stem cell |
EP3498825A1 (en) | 2010-05-12 | 2019-06-19 | Janssen Biotech, Inc. | Differentiation of human embryonic stem cells |
EP2389901B8 (en) | 2010-05-24 | 2013-05-15 | Episurf IP Management AB | An implant for cartilage repair |
EP2389900B1 (en) * | 2010-05-24 | 2013-03-27 | Episurf Medical AB | An implant for cartilage repair comprising an extending post |
EP2389899B1 (en) | 2010-05-24 | 2015-04-29 | Episurf IP Management AB | Method of manufacturing a surgical kit for cartilage repair in a joint |
EP2389904B1 (en) | 2010-05-24 | 2013-07-24 | Episurf IP Management AB | Surgical kit for cartilage repair comprising implant and a set of tools |
EP2389905B1 (en) | 2010-05-24 | 2012-05-23 | Episurf Medical AB | Method of designing a surgical kit for cartilage repair in a joint |
JP2013533319A (en) | 2010-08-12 | 2013-08-22 | ヤンセン バイオテツク,インコーポレーテツド | Treatment of diabetes with pancreatic endocrine precursor cells |
US8690956B2 (en) | 2010-08-23 | 2014-04-08 | Fellowship Of Orthopaedic Researchers, Inc. | Talar implants and methods of use |
SG187947A1 (en) | 2010-08-31 | 2013-03-28 | Janssen Biotech Inc | Differentiation of pluripotent stem cells |
WO2012030539A2 (en) | 2010-08-31 | 2012-03-08 | Janssen Biotech, Inc. | Differentiation of human embryonic stem cells |
MX355340B (en) | 2010-08-31 | 2018-04-16 | Janssen Biotech Inc | Differentiation of human embryonic stem cells. |
US8435305B2 (en) | 2010-08-31 | 2013-05-07 | Zimmer, Inc. | Osteochondral graft delivery device and uses thereof |
WO2012048275A2 (en) | 2010-10-08 | 2012-04-12 | Caridianbct, Inc. | Configurable methods and systems of growing and harvesting cells in a hollow fiber bioreactor system |
EP2640430B1 (en) * | 2010-11-17 | 2016-03-09 | Zimmer, Inc. | Ceramic monoblock implants with osseointegration fixation surfaces |
US9587064B2 (en) | 2010-12-08 | 2017-03-07 | ATRP Solutions, Inc. | Salt-tolerant star macromolecules |
WO2014121188A1 (en) | 2013-02-04 | 2014-08-07 | ATRP Solutions, Inc. | Salt-tolerant star macromolecules |
US9404087B2 (en) | 2010-12-15 | 2016-08-02 | Kadimastem Ltd. | Insulin producing cells derived from pluripotent stem cells |
US8551525B2 (en) | 2010-12-23 | 2013-10-08 | Biostructures, Llc | Bone graft materials and methods |
US8691126B2 (en) | 2011-01-18 | 2014-04-08 | Wisconsin Alumni Research Foundation | Method of fabricating an injection molded component |
EP2967665B1 (en) * | 2011-02-28 | 2020-03-25 | Tissue Regeneration Systems, Inc. | Modular tissue scaffolds |
US8771353B2 (en) | 2011-03-08 | 2014-07-08 | DePuy Synthes Products, LLC | Method and implant for replacing damaged meniscal tissue |
US9066716B2 (en) | 2011-03-30 | 2015-06-30 | Arthrosurface Incorporated | Suture coil and suture sheath for tissue repair |
KR101375828B1 (en) * | 2011-03-31 | 2014-03-17 | 인제대학교 산학협력단 | Complex Scaffold For Bone-Cartilage Regeneration, Method For Preparing Thereof And Composition for Treating Bone Cartilage Disease Comprising The Same |
SG10201901391RA (en) | 2011-05-03 | 2019-03-28 | Immunovative Therapies Ltd | Induction of il-12 using immunotherapy |
HUE034995T2 (en) | 2011-05-03 | 2018-05-02 | Immunovative Therapies Ltd | Methods for handling biological drugs containing living cells |
CH705356A2 (en) * | 2011-08-11 | 2013-02-15 | Regenhu Ag | Body with a basic structure made from bone substitute material and methods of making. |
US9351834B2 (en) | 2011-09-12 | 2016-05-31 | Biomet Manufacturing, Llc | Negative-positive pressurizable implant |
US9113879B2 (en) | 2011-12-15 | 2015-08-25 | Ethicon Endo-Surgery, Inc. | Devices and methods for endoluminal plication |
US9113866B2 (en) | 2011-12-15 | 2015-08-25 | Ethicon Endo-Surgery, Inc. | Devices and methods for endoluminal plication |
RU2705001C2 (en) | 2011-12-22 | 2019-11-01 | Янссен Байотек, Инк. | Differentiation of human embryonic stem cells into single-hormonal insulin-positive cells |
WO2013096746A1 (en) | 2011-12-22 | 2013-06-27 | Arthrosurface Incorporated | System and method for bone fixation |
JP6383292B2 (en) | 2012-03-07 | 2018-08-29 | ヤンセン バイオテツク,インコーポレーテツド | Clear media for proliferation and maintenance of pluripotent stem cells |
US8992547B2 (en) | 2012-03-21 | 2015-03-31 | Ethicon Endo-Surgery, Inc. | Methods and devices for creating tissue plications |
US9498334B2 (en) * | 2012-03-27 | 2016-11-22 | DePuy Synthes Products, Inc. | Glenoid defect-filling component |
ITUD20120059A1 (en) * | 2012-04-06 | 2013-10-07 | Limacorporate Spa | PROSTHETIC ELEMENT FOR BONE ENDS WHAT FINGERS OR TEETH AND ITS RELATION PROCEDURE |
JP6469003B2 (en) | 2012-06-08 | 2019-02-13 | ヤンセン バイオテツク,インコーポレーテツド | Differentiation of human embryonic stem cells into pancreatic endocrine cells |
US20130345826A1 (en) | 2012-06-22 | 2013-12-26 | Collagen Matrix, Inc. | Implants for Bone and Cartilage Repair |
DE112013003358T5 (en) | 2012-07-03 | 2015-03-19 | Arthrosurface, Inc. | System and procedure for joint surface replacement and repair |
US9125967B2 (en) * | 2012-11-13 | 2015-09-08 | University Of Iowa Research Foundation | Fluorapatite glass-ceramics |
US10245306B2 (en) | 2012-11-16 | 2019-04-02 | Isto Technologies Ii, Llc | Flexible tissue matrix and methods for joint repair |
WO2014089711A1 (en) * | 2012-12-11 | 2014-06-19 | Dr.H.C. Robert Mathys Stiftung | Bone substitute and method for producing same |
US20140178343A1 (en) | 2012-12-21 | 2014-06-26 | Jian Q. Yao | Supports and methods for promoting integration of cartilage tissue explants |
ES2942484T3 (en) | 2012-12-31 | 2023-06-01 | Janssen Biotech Inc | Differentiation of human embryonic stem cells into pancreatic endocrine cells using HB9 regulators |
BR112015015714A2 (en) | 2012-12-31 | 2017-07-11 | Janssen Biotech Inc | suspension and agglomeration of human pluripotent cells for differentiation into pancreatic endocrine cells |
US10370644B2 (en) | 2012-12-31 | 2019-08-06 | Janssen Biotech, Inc. | Method for making human pluripotent suspension cultures and cells derived therefrom |
ES2837763T3 (en) | 2012-12-31 | 2021-07-01 | Janssen Biotech Inc | Culture of human embryonic stem cells in the air-liquid interface for differentiation into pancreatic endocrine cells |
CN103083729B (en) * | 2013-01-28 | 2014-08-20 | 西南科技大学 | Production method of three-dimensional porous composite bar |
US9630346B2 (en) | 2013-03-05 | 2017-04-25 | Wisconsin Alumni Research Foundation | Method of fabricating an injection molded component |
US9408699B2 (en) | 2013-03-15 | 2016-08-09 | Smed-Ta/Td, Llc | Removable augment for medical implant |
US9681966B2 (en) | 2013-03-15 | 2017-06-20 | Smed-Ta/Td, Llc | Method of manufacturing a tubular medical implant |
US9724203B2 (en) | 2013-03-15 | 2017-08-08 | Smed-Ta/Td, Llc | Porous tissue ingrowth structure |
EP2983643A4 (en) | 2013-04-12 | 2016-12-28 | Univ Columbia | Methods for host cell homing and dental pulp regeneration |
US10143556B2 (en) * | 2013-04-15 | 2018-12-04 | Eisurf IP-Managment AB | System of designing a guide tool and/ or surgical kit tools and/or an implant comprising a positioning mark |
US9492200B2 (en) | 2013-04-16 | 2016-11-15 | Arthrosurface Incorporated | Suture system and method |
ITMI20130636A1 (en) * | 2013-04-18 | 2014-10-19 | Novagenit S R L | METHOD FOR THE PREPARATION OF BIO-COMPATIBLE AND BIODEGRADABLE BIOMATERIALS BASED ON COLLAGEN AND HYDROXYAPATITIS GRANULES / ¿-TRICALCOSUS PHOSPHATE FOR USE IN ORTHOPEDIC SURGERY AND BIOMATERIALS SO OBTAINED |
US9555564B2 (en) | 2013-11-11 | 2017-01-31 | Wisconsin Alumni Research Foundation | Method of fabricating a foamed, injection molded component with improved ductility and toughness |
US10633625B2 (en) | 2013-11-16 | 2020-04-28 | Terumo Bct, Inc. | Expanding cells in a bioreactor |
US10624748B2 (en) | 2014-03-07 | 2020-04-21 | Arthrosurface Incorporated | System and method for repairing articular surfaces |
US20150250472A1 (en) | 2014-03-07 | 2015-09-10 | Arthrosurface Incorporated | Delivery System for Articular Surface Implant |
US11607319B2 (en) | 2014-03-07 | 2023-03-21 | Arthrosurface Incorporated | System and method for repairing articular surfaces |
EP3122866B1 (en) | 2014-03-25 | 2019-11-20 | Terumo BCT, Inc. | Passive replacement of media |
CA2949056A1 (en) | 2014-05-16 | 2015-11-19 | Janssen Biotech, Inc. | Use of small molecules to enhance mafa expression in pancreatic endocrine cells |
US10336848B2 (en) | 2014-07-03 | 2019-07-02 | Pilot Polymer Technologies, Inc. | Surfactant-compatible star macromolecules |
WO2016044721A1 (en) | 2014-09-19 | 2016-03-24 | Regenerative Medical Solutions, Inc. | Compositions and methods for differentiating stem cells into cell populations comprising beta-like cells |
JP6830059B2 (en) | 2014-09-26 | 2021-02-17 | テルモ ビーシーティー、インコーポレーテッド | Scheduled cell feeding |
US10179191B2 (en) | 2014-10-09 | 2019-01-15 | Isto Technologies Ii, Llc | Flexible tissue matrix and methods for joint repair |
US10077420B2 (en) | 2014-12-02 | 2018-09-18 | Histogenics Corporation | Cell and tissue culture container |
US11666447B1 (en) * | 2015-03-05 | 2023-06-06 | Taq Ortho, LLC | Bone implant augment and offset device |
US11678917B1 (en) * | 2015-03-05 | 2023-06-20 | Taq Ortho, LLC | Bone insert augment and offset method |
WO2017004592A1 (en) | 2015-07-02 | 2017-01-05 | Terumo Bct, Inc. | Cell growth with mechanical stimuli |
ITUB20152661A1 (en) * | 2015-07-30 | 2017-01-30 | Tecres Spa | Antibiotic prosthetic device |
US9925298B2 (en) | 2015-10-27 | 2018-03-27 | Council Of Scientific & Industrial Research | Porous polymer scaffold useful for tissue engineering in stem cell transplantation |
US11679133B2 (en) | 2015-11-30 | 2023-06-20 | Kadimastem Ltd. | Methods for differentiating and purifying pancreatic endocrine cells |
EP3187196A1 (en) * | 2015-12-29 | 2017-07-05 | Fundacíon Tecnalia Research & Innovation | Uhmwpe-type polymer article, process for its production and implantand/or scaffold made thereof |
GB201600385D0 (en) | 2016-01-08 | 2016-02-24 | Ucl Business Plc | Osteochondral scaffold |
MA45479A (en) | 2016-04-14 | 2019-02-20 | Janssen Biotech Inc | DIFFERENTIATION OF PLURIPOTENT STEM CELLS IN ENDODERMAL CELLS OF MIDDLE INTESTINE |
EP3464565A4 (en) | 2016-05-25 | 2020-01-01 | Terumo BCT, Inc. | Cell expansion |
US11104874B2 (en) | 2016-06-07 | 2021-08-31 | Terumo Bct, Inc. | Coating a bioreactor |
US11685883B2 (en) | 2016-06-07 | 2023-06-27 | Terumo Bct, Inc. | Methods and systems for coating a cell growth surface |
US20190365956A1 (en) * | 2017-01-23 | 2019-12-05 | BONWRx, LTD. | Method and apparatus for using elastomeric materials in surgical applications |
US11624046B2 (en) | 2017-03-31 | 2023-04-11 | Terumo Bct, Inc. | Cell expansion |
WO2018184028A2 (en) | 2017-03-31 | 2018-10-04 | Terumo Bct, Inc. | Cell expansion |
US20180326123A1 (en) * | 2017-05-10 | 2018-11-15 | Board Of Trustees Of The University Of Arkansas | Biocompatible structure for tissue regeneration and methods of making and using same |
US11788062B2 (en) | 2017-07-27 | 2023-10-17 | Board Of Supervisors Of Louisiana State University And Agricultural And Mechanical College | Functional feline pancreatic cells from adipose tissue |
CA3108761A1 (en) | 2017-08-04 | 2019-02-07 | Arthrosurface Incorporated | Multicomponent articular surface implant |
US10786370B2 (en) * | 2017-12-28 | 2020-09-29 | Industrial Technology Research Institute | Cartilage repair implant, auxiliary surgical tool kit and cartilage repair system |
US20190314163A1 (en) * | 2018-04-16 | 2019-10-17 | Brahm Holdings, Llc | Spinal implant and related methods |
SE543241C2 (en) | 2018-04-27 | 2020-10-27 | Episurf Ip Man Ab | An implant for cartilage and/or bone repair |
US11478358B2 (en) | 2019-03-12 | 2022-10-25 | Arthrosurface Incorporated | Humeral and glenoid articular surface implant systems and methods |
US11565021B1 (en) * | 2019-08-12 | 2023-01-31 | Ortho Development Corporation | Composite structure porous implant for replacing bone stock |
CN112451741B (en) * | 2020-12-30 | 2022-09-09 | 杭州电子科技大学 | Bioactive stent for controlling multistage release of drugs and manufacturing method thereof |
WO2022204377A1 (en) | 2021-03-24 | 2022-09-29 | Salk Institute For Biological Studies | NOVEL CHEMICAL COMBINATIONS AND METHODS OF USE THEREOF, TOWARDS DIFFERENTIATION OF HUMAN PROGENITOR CELLS INTO FUNCTIONAL β CELLS |
Family Cites Families (59)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3929971A (en) | 1973-03-30 | 1975-12-30 | Research Corp | Porous biomaterials and method of making same |
US4057537A (en) | 1975-01-28 | 1977-11-08 | Gulf Oil Corporation | Copolymers of L-(-)-lactide and epsilon caprolactone |
US4045418A (en) | 1975-01-28 | 1977-08-30 | Gulf Oil Corporation | Copolymers of D,L-lactide and epsilon caprolactone |
US4186448A (en) | 1976-04-16 | 1980-02-05 | Brekke John H | Device and method for treating and healing a newly created bone void |
US4141087A (en) | 1977-01-19 | 1979-02-27 | Ethicon, Inc. | Isomorphic copolyoxalates and sutures thereof |
US4208511A (en) | 1977-01-19 | 1980-06-17 | Ethicon, Inc. | Isomorphic copolyoxalates and sutures thereof |
US4105034A (en) | 1977-06-10 | 1978-08-08 | Ethicon, Inc. | Poly(alkylene oxalate) absorbable coating for sutures |
US4140678A (en) | 1977-06-13 | 1979-02-20 | Ethicon, Inc. | Synthetic absorbable surgical devices of poly(alkylene oxalates) |
US4205399A (en) | 1977-06-13 | 1980-06-03 | Ethicon, Inc. | Synthetic absorbable surgical devices of poly(alkylene oxalates) |
US4130639A (en) | 1977-09-28 | 1978-12-19 | Ethicon, Inc. | Absorbable pharmaceutical compositions based on isomorphic copolyoxalates |
US4479271A (en) * | 1981-10-26 | 1984-10-30 | Zimmer, Inc. | Prosthetic device adapted to promote bone/tissue ingrowth |
US5133755A (en) | 1986-01-28 | 1992-07-28 | Thm Biomedical, Inc. | Method and apparatus for diodegradable, osteogenic, bone graft substitute device |
FI80605C (en) | 1986-11-03 | 1990-07-10 | Biocon Oy | Bone surgical biocomposite material |
CA1340581C (en) | 1986-11-20 | 1999-06-08 | Joseph P. Vacanti | Chimeric neomorphogenesis of organs by controlled cellular implantation using artificial matrices |
DE3644588C1 (en) | 1986-12-27 | 1988-03-10 | Ethicon Gmbh | Implant and process for its manufacture |
US4861733A (en) | 1987-02-13 | 1989-08-29 | Interpore International | Calcium phosphate bone substitute materials |
US5306311A (en) | 1987-07-20 | 1994-04-26 | Regen Corporation | Prosthetic articular cartilage |
GB2215209B (en) | 1988-03-14 | 1992-08-26 | Osmed Inc | Method and apparatus for biodegradable, osteogenic, bone graft substitute device |
US5108755A (en) * | 1989-04-27 | 1992-04-28 | Sri International | Biodegradable composites for internal medical use |
US5067964A (en) | 1989-12-13 | 1991-11-26 | Stryker Corporation | Articular surface repair |
GB8928250D0 (en) | 1989-12-14 | 1990-02-21 | Erba Carlo Spa | Use of supercritical fluids to obtain porous sponges of biodegradable polymers |
US5486359A (en) | 1990-11-16 | 1996-01-23 | Osiris Therapeutics, Inc. | Human mesenchymal stem cells |
JP3007903B2 (en) | 1991-03-29 | 2000-02-14 | 京セラ株式会社 | Artificial disc |
US5502159A (en) | 1991-04-17 | 1996-03-26 | United States Surgical Corporation | Absorbable composition |
US5225520A (en) | 1991-04-17 | 1993-07-06 | United States Surgical Corporation | Absorbable composition |
JPH07503869A (en) | 1992-02-14 | 1995-04-27 | ボード・オヴ・リージェンツ,ザ・ユニヴァーシティ・オヴ・テキサス・システム | Multiphasic bioerodible implant materials or carriers and methods of manufacture and use thereof |
US5468253A (en) | 1993-01-21 | 1995-11-21 | Ethicon, Inc. | Elastomeric medical device |
US5514378A (en) | 1993-02-01 | 1996-05-07 | Massachusetts Institute Of Technology | Biocompatible polymer membranes and methods of preparation of three dimensional membrane structures |
US5403347A (en) | 1993-05-27 | 1995-04-04 | United States Surgical Corporation | Absorbable block copolymers and surgical articles fabricated therefrom |
US5522895A (en) | 1993-07-23 | 1996-06-04 | Rice University | Biodegradable bone templates |
WO1995005083A1 (en) | 1993-08-13 | 1995-02-23 | Smith & Nephew Richards Inc | Microporous polymeric foams and microtextured surfaces |
DE69426414T2 (en) | 1993-09-24 | 2001-05-03 | Takiron Co | IMPLANT MATERIAL |
US5431679A (en) | 1994-03-10 | 1995-07-11 | United States Surgical Corporation | Absorbable block copolymers and surgical articles fabricated therefrom |
US5686091A (en) | 1994-03-28 | 1997-11-11 | The Johns Hopkins University School Of Medicine | Biodegradable foams for cell transplantation |
US5632745A (en) | 1995-02-07 | 1997-05-27 | R&D Biologicals, Inc. | Surgical implantation of cartilage repair unit |
US5769899A (en) | 1994-08-12 | 1998-06-23 | Matrix Biotechnologies, Inc. | Cartilage repair unit |
US5749874A (en) | 1995-02-07 | 1998-05-12 | Matrix Biotechnologies, Inc. | Cartilage repair unit and method of assembling same |
US5713374A (en) | 1995-02-10 | 1998-02-03 | The Hospital For Joint Diseases Orthopaedic Institute | Fixation method for the attachment of wound repair materials to cartilage defects |
US5700583A (en) | 1995-03-06 | 1997-12-23 | Ethicon, Inc. | Hydrogels of absorbable polyoxaesters containing amines or amido groups |
US5698213A (en) | 1995-03-06 | 1997-12-16 | Ethicon, Inc. | Hydrogels of absorbable polyoxaesters |
US5597579A (en) | 1995-03-06 | 1997-01-28 | Ethicon, Inc. | Blends of absorbable polyoxaamides |
US5607687A (en) | 1995-03-06 | 1997-03-04 | Ethicon, Inc. | Polymer blends containing absorbable polyoxaesters |
US5464929A (en) | 1995-03-06 | 1995-11-07 | Ethicon, Inc. | Absorbable polyoxaesters |
US5648088A (en) | 1995-03-06 | 1997-07-15 | Ethicon, Inc. | Blends of absorbable polyoxaesters containing amines and/or amide groups |
US5595751A (en) | 1995-03-06 | 1997-01-21 | Ethicon, Inc. | Absorbable polyoxaesters containing amines and/or amido groups |
US5859150A (en) | 1995-03-06 | 1999-01-12 | Ethicon, Inc. | Prepolymers of absorbable polyoxaesters |
US5618552A (en) | 1995-03-06 | 1997-04-08 | Ethicon, Inc. | Absorbable polyoxaesters |
US5716413A (en) | 1995-10-11 | 1998-02-10 | Osteobiologics, Inc. | Moldable, hand-shapable biodegradable implant material |
GB9522478D0 (en) * | 1995-11-02 | 1996-01-03 | Howmedica | Prosthetic bearing element and implant incorporating such an element |
US5723508A (en) | 1996-01-25 | 1998-03-03 | Northwestern University | Method of fabricating emulsion freeze-dried scaffold bodies and resulting products |
US6296667B1 (en) | 1997-10-01 | 2001-10-02 | Phillips-Origen Ceramic Technology, Llc | Bone substitutes |
US6136029A (en) | 1997-10-01 | 2000-10-24 | Phillips-Origen Ceramic Technology, Llc | Bone substitute materials |
NL1010248C1 (en) | 1998-10-05 | 2000-04-06 | Armand Francois Victor Mathijs | Method for impregnating porous, stony objects. |
EP1027897B1 (en) | 1999-02-10 | 2005-04-13 | IsoTis N.V. | Cartillage tissue engineering |
US6103255A (en) | 1999-04-16 | 2000-08-15 | Rutgers, The State University | Porous polymer scaffolds for tissue engineering |
US6251143B1 (en) | 1999-06-04 | 2001-06-26 | Depuy Orthopaedics, Inc. | Cartilage repair unit |
DE19933382A1 (en) | 1999-07-16 | 2001-02-01 | Eska Implants Gmbh & Co | Filling implant for cartilage and bone defects in one joint |
JP2003516803A (en) | 1999-12-15 | 2003-05-20 | ズルツァー・オルトペディクス・リミテッド | Device for repairing cartilage defects or cartilage / bone defects in human or animal joints |
US20020183858A1 (en) | 2001-06-05 | 2002-12-05 | Contiliano Joseph H. | Attachment of absorbable tissue scaffolds to scaffold fixation devices |
-
2001
- 2001-06-28 US US09/893,813 patent/US6626950B2/en not_active Expired - Lifetime
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2002
- 2002-06-25 AU AU48942/02A patent/AU784508B2/en not_active Ceased
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