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This invention relates to endoprostheses.
The body includes various passageways such as arteries, other blood vessels, and other body lumens. These passageways sometimes become occluded or weakened. For example, the passageways can be occluded by a tumor, restricted by plaque, or weakened by an aneurysm. When this occurs, the passageway can be reopened or reinforced with a medical endoprosthesis. An endoprosthesis is typically a tubular member that is placed in a lumen in the body. Examples of endoprostheses include stents, covered stents, and stent-grafts.
Endoprostheses can be delivered inside the body by a catheter that supports the endoprosthesis in a compacted or reduced-size form as the endoprosthesis is transported to a desired site. Upon reaching the site, the endoprosthesis is expanded, e.g., so that it can contact the walls of the lumen. Stent delivery is further discussed in Heath, U.S. Pat. No. 6,290,721, the entire contents of which is hereby incorporated by reference herein.
The expansion mechanism may include forcing the endoprosthesis to expand radially. For example, the expansion mechanism can include the catheter carrying a balloon, which carries a balloon-expandable endoprosthesis. The balloon can be inflated to deform and to fix the expanded endopro sthesis at a predetermined position in contact with the lumen wall. The balloon can then be deflated, and the catheter withdrawn from the lumen.
In an aspect the invention features a stent including a stent body and a wire-form carrying a drag passing through and located along the stent body.
In an aspect, the invention features a stent including a stent body formed of metal and a wire-form formed of metal, the wire-form carrying a drug and located along the stent body.
Embodiments may include one or more of the following features. The wire-form has a diameter of about 20 micron or less. The stent body includes fenestrations and the wire-form is located in the fenestrations. The wire-form passes through the fenestrations. The wire-form passes through a passage in the stent body. The wire-form is substantially freely slideable through the passage. The wire-form is a ceramic, metal or polymer. The drug is coated on the wire-form. The drug is in a polymer carrier. The drug is in a capsule. The wire-form is composed of multiple wire-forrns joined together. The drug is provided between individual wire-forms.
Embodiments may include one or more of the following features. The wire-form extends beyond an end of the stent. The stent includes multiple wire-form strands. The density of the strands varies along the stent body. The stent body is substantially free of drug. The stent body includes an endothelialization-enhancing material on its surface. The endothelialization-enhancing material is a ceramic. The wire-form is bioerodible. The wire-form is biostable. The stent body and wire-form are formed of the same material, e.g., the same metal.
Embodiments may include one or more of the following advantages. A stent may be provided that has enhanced therapeutic, particularly drug delivery, capabilities. The drug may
be carried by a thin, wire like element instead of or in addition to being on the stent body. The drug is carried by the stent but decoupled from the stent body surface. As a result, the distribution of drug delivery is not limited to the stent geometry or position of the stent wall against the vessel. Neither the stent body nor drug coating design need to be compromised to, e. g., enhance adhesion of the coating to the stent to prevent delamination. The surface of the stent wall can be optimized to enhance endothelialization. For example, the stent wall may include a ceramic coating that encourages endothelialization. In addition, more effective drug distribution beyond the vessel wall, e.g., within the fenestrated areas of the stent and/or beyond the proximal and distal ends of the stent body may be achieved. Still further aspects, features, and advantages follow.
FIGS. 1A-1C are longitudinal cross-sectional views illustrating delivery of a stent in a collapsed state, expansion of the stent, and deployment of the stent.
FIG. 2A is a side view ofa stent.
FIG. 2B is an enlarged perspective cross-sectional view of region A in FIG. 2A.
FIGS. 3A-3C are enlarged cross sections of a stent strut.
FIG. 4 is a cross section ofa wire-form.
FIG. 5A is a schematic of a stent during processing, while FIG. 5B is a schematic of the stent post-processing.
Like reference symbols in the various drawings indicate like elements.
Referring to FIG. 1A, a stent 20 is placed over a balloon 12 carried near a distal end of a catheter 14, and is directed through the lumen 16 (FIG. 1A) until the portion carrying the balloon and stent reaches the region of an occlusion 18. The stent 20 is then radially expanded by inflating the balloon 12 and compressed against the vessel wall with the result that occlusion 18 is compressed, and the vessel wall surrounding it undergoes a radial expansion (FIG. 1B). The pressure is then released from the balloon and the catheter is withdrawn from the vessel (FIG. 1C).
Referring to FIG. 2A, the stent 20 includes a stent body 22 shaped to define open areas or fenestrations 24. The stent body 22 extends from a proximal end 26 to a distal end 28. The stent body 22 can be formed e.g. of a metal, ceramic, or polymer. In particular embodiments, the metal is biostable, e.g. a stainless steel, niobium, tantalum or a superelastic metal e.g. a nitinol or biodegradable, e.g. magnesium, iron or tungsten. Further discussion of stents and stent delivery is provided in Heath, incorporated supra.
Referring as well to FIG. 2B, in embodiments, the stent body 22 is free of a drug coating and the stent includes a series of wire strands 30, 32, 34, 36 which carry a drug. The wires are elongate filament-forms that can extend over the stent body and can be woven through the fenestrations and/or through passageways 38 in the stent body. The wires can be formed of a metal, ceramic or a polymer. The drug can be contained within the wires or coated on the outside of the wires, e.g. in a drug eluting polymer coating. In embodiments, the drug eluting wire can include regions 40, in this embodiment loops, extending beyond the proximal and distal ends of the stent body.
The wires can be substantially smaller in cross-sectional dimensions than the stent body such that they do not substantially interfere with the mechanical performance of the stent
body. The wires can be positioned along the stent to provide a desirable number or density at wires of desired locations along the stent. The wires can be provided at a higher density than the stent body to create a more uniform drug release profile, including within the fenestrated areas. The release profile can be selected independently of the stent body pattern. The wires can be woven to provide suflicient slack such that the wires do not inhibit expansion of the stent. The wires can extend beyond the ends of the stent, e.g. by forming loops, such that drug can be delivered beyond the ends of the stent body. A single continuous wire can be woven about the stent or multiple separate wires can be provided.
Referring to FIGS. 3A-3C, passageways 38, 38', 38" in the stent body can be, respectively, from one side surface to the other, from the outside surface to a side surface, from a side surface to an inside surface or from an outside surface to an inside surface (not shown). The passageways can be formed by laser drilling. The wires can be slideable within the passageways or can be friction fit or glued to the passageways or otherwise to the stent body. In embodiments, the wires can be tied with a knot larger than the passageway to prevent the wire from being pulled through the passageway. The wires can also be looped through the fenestrations and around the stent body and tied to hold the wires to the stent. A network of thin wires along the side-wall of stents can be formed by using two thin stents and crimping one inside of the other placing the wire network in between (like a sandwich). The two stent parts can be either glued, fused, and/or a self-expanding inner stent can be provided inside of a metal balloon expandable stent on a balloon.
In embodiments, the wires have a diameter substantially less than the thickness of the stent wall, e.g. about 20% or less, e.g. 10% or less, e.g. about 0.1 to 5%. In embodiments, the diameter is about 20 micron or less, e.g. 15 micron or less, e.g. 1-10 micron. The wires can be relatively floppy or stiff. For wires that extend beyond the ends of the stent, it is desirable the wires stay close to the vessel wall either by this areas with a higher inflammation. Further discussion of Selectins is in Eniola et al., Biomaterials 26:661-670 (2005).
The drug is incorporated within and/ or deposited on top of the wires. This can be done prior to weaving the wires through the passageways and struts, or one could attach the drug post weaving. For example, the wire can be drawn through a solution containing the drug or the drug with a matrix polymer. Damage to the coating while weaving the wire through the structure can be achieved by freezing the polymer to below its glass-transition temperature. The drug can be applied to the wire after the wire has been weaved through the stent structure, by dispensing small droplets directly to the wire. In case of a polymeric or ceramic wire, drug can be applied using electrostatic spraying. A positively charged mandrel is provided inside of the stent (not in direct contact with the stent), charges the stents negative and uses a negatively charged spray. As the spray is attracted by the core wire, it will be deflected by the stent struts, flying through the openings to the core wires, however meanwhile hitting the non-charged woven wire. The holes within the strut can be made by means of an excimer or a UV laser and ultrashort pulse (pico, femto, atto) lasers. The wire can be manipulated by hand or by automated techniques. Suitable techniques are described by, for example, the CSEM (Centre Suisse d’Electronique et de Microtechnique). Referring to FIG. 4, a string of three or more ultrafine wires 50, 51, 52 can be woven, twisted or braided, and the drug/polymer coating 53 positioned over and with the inner spaces of the braided structure between the individual wires.
Referring to FIGS. 5A and 5B, the drug can be incorporated within drug release controlling and fully biodegradable capsules 70. These capsules are made using polyelectric layers and the outermost shell can therefore be made both positive as well as negatively charged. Suitable capsules are described in U.S. Published Patent Application No. 2005/ 0129727. Polyelectric layer techniques are described in U.S. Patent Application No. 60/845,136, filed Sep. 15, 2006. The wires can be covered with a couple of polyelectrolytic layers before weaving them through the stent structure. These layers by themselves are very thin (e.g. single nanometers) as well as robust and will survive the mechanical friction as encountered weaving the wires through the holes. After the wires have been added to the stent, the stent plus wires are dipped into a stiffness and/ or the flow of body fluid through the stent. In embodiments, the wires can extend beyond the stent by about 5%, e.g. 10% or more than the length of the stent body. In embodiments, the wires extend about 0.2 to 1 cm beyond the ends of the stent. The wires can be formed of metal, ceramic, or polymer. The wires can be formed of the same material as the stent body or different material. The wires can be biostable or bioerodible. In particular embodiments, particularly with wires using biostable metals, the wires are formed of the same material as the stent body to reduce galvanic corrosion effects. In other embodiments, in which bioerosion is desireable, the stent body and wire can be formed of different metals to encourage galvanic corrosion. Suitable metals include stainless steel, niobium, titanium, magnesium, iron, and tungsten. Stainless steel wires with single micrometer diameter can be obtained from Bekaert (Belgium). Stainless steel wires are also described in Wang et al., Materials Science and Technology, 2005 Vol. 21(01) 1323. Ceramic (Alumina-oxide) fibers with diameters of 10-12 micrometer can be obtained from 3M (St. Paul, Minn.). Polymeric fibers with small dimensions can be made of dissolvable polymers using electro-spinning (see A review on polymer nanofibers by electro-spinning and their applications in nanocomposites. Composites Science and Technology 63 (2003) 2223-2253). Suitable polymers are described in US2005/0165470. The polymer may be bioerodible such that it disintegrates in a desired time in the body. In a particular embodiment wire is made out of PLGA with an embedded drug and coated as well with biotinylataead-Sialyl LewisX (sLeX), a carbohydrate that serves as a ligant to selectins, mimicing the adhesive behavior of leukocytes on selectins. The site-specific expression of selectins (P- and E-selectin) on endothelial cells of blood vessels during inflammation provides an opportunity for the targeted delivery of antiinflammatory drugs to sites of chronic inflammation. Selectins mediate the initial interaction (rolling) of leukocytes in an inflamed vessel by binding to carbohydrate-presenting counterreceptors displayed on leukocytes. A ring or stent can be placed just proximal to a site of inflammation. Micro sized PLGA (or PLGA coated iron) wires provided on the stent or ring are coated with the (sLeX). The ends of the drug wires are allowed to extend beyond the stent or ring, flowing downstream with blood flow (anchored by the ring). Most of the wires attach themselves to the vessel wall at the location of an inflammation, providing as such a coating which self redistributes itself to solution 72 containing the drug filled capsules 70, whereby these would assemble themselves to the wires given that the charge on the wires and the charge on the capsule is opposite. As the stent surface is non-charged, no capsules will assemble on the stent surface. Optionally, different wires can be coated with different outer coating such that at a given pH, one could only coat specific wires with these capsules and other capsules with other capsules. In