ABSORBABLE INTRAVASCULAR DEVICES FOR THE TREATMENT OF VENOUS OCCLUSIVE DISEASE

Abstract

A venous stent may be used to maintain or enhance patency of a blood vessel. By using multiple, separate stent elements that are balloon expandable, the multi-element stent may be stronger than a traditional self-expanding stent but may also be more flexible, due to its multiple-element configuration, than a traditional balloon-expandable stent. The stent elements are formed from a bioresorbable polymer material. The stent elements may have thick and/or wide struts and may be deployed oversized so as to overcome venous elastic recoil and anatomic compression.

Claims

1. A device for placement within a vein to maintain or enhance blood flow through the vein comprising: multiple, balloon-expandable, bioresorbable, venous stent elements configured to be implanted in the vein as a multi-element stent, wherein the stent elements are spaced such that the stent elements do not touch one another; wherein the stent elements are formed from a bioresorbable polymer material; wherein the stent elements are configured to provide temporary, rigid, radial support to the vein following balloon angioplasty; wherein the stent elements comprise helically aligned adjacent rhombus shaped closed cells of equal size; wherein the stents elements have a thickness of approximately 425 microns or more; and wherein the stent elements are formed by struts having a width of approximately 425 microns or more.

2. The device of claim 1, further comprising a therapeutic drug, wherein the therapeutic drug prevents or attenuates inflammation, cell dysfunction, cell activation, cell proliferation, neointimal formation, thickening, late atherosclerotic change or thrombosis.

3. The device of claim 1, wherein the bioresorbable polymer material comprises poly(L-lactic acid) (PLLA), poly(D-lactic acid) (PDLA), poly(D,L-lactic acid) (PDLLA), semi crystalline polylactide, polyglycolic acid (PGA), poly(lactic-co-glycolic acid) (PLGA), poly(iodinated desamino tyrosyl-tyrosine ethyl ester) carbonate, polycaprolactone (PCL), salicylate based polymer, polydioxanone (PDS), poly(hydroxybutyrate), poly(hydroxybutyrate-co-valerate), polyorthoester, polyanhydride, poly(glycolic acid-co-trimethylene carbonate), poly(iodinated desaminotyrosyl-tyrosine ethyl ester) carbonate, polyphosphoester, polyphosphoester urethane, poly(amino acids), cyanoacrylates, poly(trimethylene carbonate), poly(iminocarbonate), polyalkylene oxalates, polyphosphazenes, polyiminocarbonates, and aliphatic polycarbonates, fibrin, fibrinogen, cellulose, starch, collagen, polyurethane including polycarbonate urethanes, polyethylene, polyethylene terephthalate, ethylene vinyl acetate, ethylene vinyl alcohol, silicone including polysiloxanes and substituted polysiloxanes, polyethylene oxide, polybutylene terephthalate-co-PEG, PCL-co-PEG, PLA-co-PEG, PLLA-co-PCL, polyacrylates, polyvinyl pyrrolidone, polyacrylamide, or combinations thereof

4. The device of claim 1, wherein the radial rigidity of the stent is slowly attenuated as its structural polymer is unlinked and metabolized such that the stent slowly becomes more flexible causing adaptation and remodeling of the vein and restoration of the vein's elasticity.

5. The device of claim 1, wherein the rhombus shaped closed cells have circular keyhole shaped corners.

6. A method for maintaining or enhancing blood flow through a vein comprising: implanting a balloon-expandable multi-element venous stent within a vein at a target location, wherein the venous stent comprises multiple bioresorbable venous stent elements spaced such that the stent elements do not touch one another; wherein the venous stent is expanded using a balloon to a diameter larger than the diameter of the vein at the target location; wherein the stent elements are formed from a bioresorbable polymer material; wherein the stent elements are configured to provide temporary, rigid, radial support to the vein following implantation; wherein the stent elements comprise helically aligned adjacent rhombus shaped closed cells of equal size; wherein the stents elements have a thickness of approximately 425 microns or more; and wherein the stent elements are formed by struts having a width of approximately 425 microns or more.

7. The method of claim 6, wherein the venous stent further comprising a therapeutic drug, wherein the therapeutic drug prevents or attenuates inflammation, cell dysfunction, cell activation, cell proliferation, neointimal formation, thickening, late atherosclerotic change or thrombosis.

8. The method of claim 6, wherein the bioresorbable polymer material comprises poly(L-lactic acid) (PLLA), poly(D-lactic acid) (PDLA), poly(D,L-lactic acid) (PDLLA), semi crystalline polylactide, polyglycolic acid (PGA), poly(lactic-co-glycolic acid) (PLGA), poly(iodinated desamino tyrosyl-tyrosine ethyl ester) carbonate, polycaprolactone (PCL), salicylate based polymer, polydioxanone (PDS), poly(hydroxybutyrate), poly(hydroxybutyrate-co-valerate), polyorthoester, polyanhydride, poly(glycolic acid-co-trimethylene carbonate), poly(iodinated desaminotyrosyl-tyrosine ethyl ester) carbonate, polyphosphoester, polyphosphoester urethane, poly(amino acids), cyanoacrylates, poly(trimethylene carbonate), poly(iminocarbonate), polyalkylene oxalates, polyphosphazenes, polyiminocarbonates, and aliphatic polycarbonates, fibrin, fibrinogen, cellulose, starch, collagen, polyurethane including polycarbonate urethanes, polyethylene, polyethylene terephthalate, ethylene vinyl acetate, ethylene vinyl alcohol, silicone including polysiloxanes and substituted polysiloxanes, polyethylene oxide, polybutylene terephthalate-co-PEG, PCL-co-PEG, PLA-co-PEG, PLLA-co-PCL, polyacrylates, polyvinyl pyrrolidone, polyacrylamide, or combinations thereof

9. The method of claim 6, wherein the radial rigidity of the stent is slowly attenuated as its structural polymer is unlinked and metabolized such that the stent slowly becomes more flexible causing adaptation and remodeling of the vein and restoration of the vein's elasticity.

10. The method of claim 6, wherein the rhombus shaped closed cells have circular keyhole shaped corners.

11. The method of claim 6, wherein the venous stent is expanded to a diameter 2.5% or more larger than the diameter of the vein at the target location.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0044] Present embodiments have other advantages and features which will be more readily apparent from the following detailed description and the appended claims, when taken in conjunction with the accompanying drawings, in which:

[0045] FIG. 1A illustrates one embodiment of a multi-element stent.

[0046] FIG. 1B is a magnified view of the stent elements in FIG. 1A.

[0047] FIGS. 2A depicts deployment of a balloon-expandable multi-element stent.

[0048] FIG. 2B depicts deployment of a balloon-expandable multi-element stent.

[0049] FIG. 2C depicts deployment of a balloon-expandable multi-element stent.

[0050] FIG. 3A is a two-dimensional depiction of an element of a stent pattern.

[0051] FIG. 3B shows a magnified views of the cells in FIG. 3A.

[0052] FIG. 3C shows the stent element of FIG. 3A in cylindrical form.

[0053] FIG. 3D shows a magnified views of the cells in FIG. 3A.

[0054] FIG. 3E shows a magnified views of the cells in FIG. 3A.

[0055] FIG. 3F shows the stent element of FIG. 3A in cylindrical form.

[0056] FIG. 4A shows an embodiment of a stent pattern having diamond shaped cells with rounded corners.

[0057] FIG. 4B shows an embodiment of stent pattern having diamond shaped cells with circular keyhole shaped corners.

[0058] FIG. 4C shows an embodiment of stent pattern having diamond shaped cells with circular keyhole shaped corners.

[0059] FIG. 4D shows an embodiment of stent pattern having diamond shaped cells with circular keyhole shaped corners.

[0060] FIG. 5A is a two-dimensional depiction of an element of a stent pattern.

[0061] FIG. 5B shows a magnified view of the cells in FIG. 5A.

[0062] FIG. 5C shows the stent element of FIG. 5A in cylindrical form.

[0063] FIG. 5D shows the stent element of FIG. 5A in cylindrical form.

[0064] FIG. 6A show finite element analysis of a bioresorbable venous stent.

[0065] FIG. 6B show finite element analysis of a bioresorbable venous stent.

[0066] FIG. 6C show finite element analysis of a bioresorbable venous stent.

[0067] FIG. 6D show finite element analysis of a bioresorbable venous stent.

[0068] FIG. 6E show finite element analysis of a bioresorbable venous stent.

[0069] FIG. 6F show finite element analysis of a bioresorbable venous stent.

[0070] FIGS. 7A-7E show deployment of a segmented, rigid, absorbable scaffold in the right porcine iliofemoral vein.

[0071] FIG. 8 is a schematic diagram of a micro-stereolithograph used to create a stent, according to one embodiment.

[0072] FIG. 9 shows a bioresorbable venous stent crimped onto a delivery balloon.

[0073] FIG. 10 shows an optical coherence tomographic (OCT) image of a venous stent deployed into a porcine iliofemoral vein.

DETAILED DESCRIPTION

[0074] While the invention has been disclosed with reference to certain embodiments, it will be understood by those skilled in the art that various changes may be made and equivalents may be substituted without departing from the scope of the invention. In addition, many modifications may be made to adapt to a particular situation or material to the teachings of the invention without departing from its scope.

[0075] Throughout the specification and claims, the following terms take the meanings explicitly associated herein unless the context clearly dictates otherwise. The meaning of “a”, “an”, and “the” include plural references. The meaning of “in” includes “in” and “on.” Referring to the drawings, like numbers indicate like parts throughout the views. Additionally, a reference to the singular includes a reference to the plural unless otherwise stated or inconsistent with the disclosure herein.

[0076] The word “exemplary” is used herein to mean “serving as an example, instance, or illustration.” Any implementation described herein as “exemplary” is not necessarily to be construed as advantageous over other implementations.

[0077] Various embodiments are described herein with reference to the figures. The figures are not drawn to scale and are only intended to facilitate the description of the embodiments. They are not intended as an exhaustive description of the invention or as a limitation on the scope of the invention. In addition, an illustrated embodiment needs not have all the aspects or advantages shown. An aspect or an advantage described in conjunction with a particular embodiment is not necessarily limited to that embodiment and can be practiced in any other embodiments even if not so illustrated.

[0078] A typical “bioresorbable vascular scaffold” (BVS) or absorbable stent has a radial resistive force of under 2 N/cm. Similarly, a typical self-expanding metal stent (SES) has a radial resistive force of under 2 N/cm. Typical balloon-expandable metal stents (BES) have a much higher radial resistive force, sometimes above 18 N/cm. The polymer, shape, cell pattern, thickness, and/or width of the stent elements may be configured to have a radial resistive force of 18 N/cm or more after implantation in the vein.

[0079] The embodiments herein describe the design of a new, intravascular absorbable device that maintains the flow channel (patency) of blood vessels by providing temporary, rigid, radial support that is far greater than that provided by a typical absorbable or metal self-expanding stent (SES) and commensurate with that provided by a metal balloon-expandable stent (BES). Once implanted, the absorbable device imparts a high degree of radial force to prop open the diseased vein; the force is roughly equivalent to a large diameter, peripheral, balloon-expandable metal stent.

[0080] In contrast to most stent patterns which are designed to marry both radial force and longitudinal flexibility, the patterns described herein are specifically tailored to maximize radial force and rigidity and forego longitudinal and axial flexibility.

[0081] The devices described herein are multi-element, vascular stents (or “vascular scaffolds”). These stents are comprised of multiple, short, rigid, cylindrical stent segments, or elements, which are separate from one another but may be referred to together as a multi-element stent.

[0082] Generally, each element of the multi-element stents described herein will be sufficiently rigid to provide a desired level of strength to withstand the stresses of the vessel in which they are placed, such as a tortuous peripheral vessel. At the same time, a multi element stent will also be flexible, due to the fact that it is made up of multiple separate elements, thus allowing for placement within a curved, torturous blood vessel.

[0083] Additionally, the multi element stents described herein will usually be balloon-expandable rather than self-expanding, since balloon-expandable stents are typically stronger than self-expanding stents. Each balloon expandable element of the stent may have relatively high radial force (rigidity) due to the described structures and materials. A stent element is defined as being radially rigid if it has a radial strength significantly higher than self-expanding stents that is similar or greater in magnitude to that of traditional, metal balloon-expandable stents, such as those made of steel or cobalt-chromium.

[0084] When mounted serially on an inflatable balloon, they can be simultaneously implanted side-by-side in long blood vessels. During motion of the organism, the elements can move independently, maintaining their individual shape and strength while the intervening, non-stented elements of the vessel can twist, bend and rotate unencumbered. The result is a treated vessel with a rigidly maintained flow channel that still enjoys unrestricted flexibility during organismal movement.

[0085] The described embodiments exploit the principles that, (1) a rigid device that is deployed via balloon-expansion represents the optimal design of an intravascular stent given its transient effect on the venous wall and relative ease of precise implantation, (2) a long, rigid device cannot be safely implanted in an vein that bends and twists with skeletal motion, (3) long veins that bend and twist could be effectively treated with multiple, short BES that allow the intervening, non-stented venous elements to move unencumbered, (4) the length, number and spacing of the stent elements could be determined by the known and predictable bending characteristics of the target veins, and (5) veins need only be scaffolded transiently; late dissolution of the stent will have little effect on the long-term effectiveness of treatment.

[0086] Various embodiments herein describe the design of a new, intravascular absorbable device that maintains the flow channel (patency) of systemic veins by providing temporary, rigid, radial support. Once implanted, the absorbable device imparts a high degree of radial force to prop open the diseased vein. The device may be indicated for the treatment of long, occlusive lesions in bendable human veins. The device may be used to treat pathologic conditions of both peripheral veins (with diameters ranging from 5 mm to 12 mm) and central veins (with diameters ranging from 8 mm to 16 mm). In various embodiments, the device is configured to be implanted in the femoral vein, deep femoral vein, popliteal vein, common femoral vein, fibular veins, anterior tibial vein, posterior tibial vein, peroneal veins, great saphenous vein, small saphenous vein, subclavical vein, subscapular vein, axililary vein, cephalic vein, medial cubital vein, basalic vein, median antebrachial vein, radial vein, ulnar vein, brachial vein, common iliac vein, internal iliac vein, external iliac vein, splenic vein, superior mesenteric vein, superior vena cava, inferior vena cava, brachiocephalic vein, azygos vein, internal jugular vein, external jugular vein, vertebral vein, renal vein, uterine vein, pelvic vein, or ovarian vein. The device may be fashioned as a series of identical or near-identical rigid elements that are evenly spaced on a single, long balloon. The venous stent is expanded using a balloon to a diameter larger than the diameter of the vein at the target location. In various embodiments, the stent may be expanded to a diameter 1% or more greater than the diameter of the vein at the target location, 2% or more greater than the diameter of the vein at the target location, 2.5% or more greater than the diameter of the vein at the target location, 2.5%-5% greater than the diameter of the vein at the target location, 5%-7.5% greater than the diameter of the vein at the target location, 7.5%-10% greater than the diameter of the vein at the target location, 10%-12.5% greater than the diameter of the vein at the target location, 12.5%-15% greater than the diameter of the vein at the target location, 15%-17.5% greater than the diameter of the vein at the target location, 17.5%-20% greater than the diameter of the vein at the target location, 20%-22.5% greater than the diameter of the vein at the target location, 22.5%-25% greater than the diameter of the vein at the target location, 25%-27.5% greater than the diameter of the vein at the target location, 27.5%-30% greater than the diameter of the vein at the target location, or 30% or more greater than the diameter of the vein at the target location.

[0087] Drug-eluting bioresorbable scaffolds described herein with high radial strength represent an attractive option for the treatment of failing dialysis access grafts. They can provide firm scaffolding which return the vein to its original diameter, restore brisk blood, resist venous recoil, attenuate restenosis and, most importantly, soften over time preserving venous movement and facilitating the repetitive percutaneous access required for ongoing dialysis.

[0088] One embodiment of the fully assembled device in shown in FIG. 1A. A single balloon inflation and device deployment can treat a long segment of diseased vein while still preserving the critical ability of the vein to bend with skeletal motion such as sitting or walking. Multi-element stent 100 comprises multiple stent elements 101. Individual balloon-expandable stent elements 101 are crimped onto an inflatable balloon 103 to facilitate delivery. FIG. 1B is a magnified view of the stent elements 101 in FIG. 1A. Individual elements 101 are positioned serially along a longitudinal length of the balloon 103 and spaced such that the stent elements 101 do not touch one another. Further, the spacing is such that after deployment, the stent elements 101 do not touch or overlap during skeletal movement. The number of elements 101, length of elements 101, and gap 102 between elements 101 may vary depending on the target vessel location. In an embodiment, each element 101 in the multi-element stent 100 has the same length. In multi-element stents having three or more elements 101, and thus two or more gaps 102, the gaps may be of the same length.

[0089] FIGS. 2A-2C depict deployment of a balloon-expandable multi-element stent. In FIG. 2A a multi-element stent mounted on a balloon is advanced to the lesion. In FIG. 2B the balloon and stent are expanded. In FIG. 2C the balloon is withdrawn leaving the multi-element stent still within the vein.

[0090] The stents described herein may be formed from various different materials. In an embodiment, stents may be formed a polymer. In various alternative embodiments, the stent or stent element may be made from any suitable bioresorbable material such that it will dissolve non-toxically in the human body, such as but not limited to poly(L-lactic acid) (PLLA), polyglycolic acid (PGA), poly(iodinated desaminotyrosyl-tyrosine ethyl ester) carbonate, or the like.

[0091] In alternative embodiments, any suitable polymer may be used to construct the stent. The term “polymer” is intended to include a product of a polymerization reaction inclusive of homopolymers, copolymers, terpolymers, etc., whether natural or synthetic, including random, alternating, block, graft, branched, cross-linked, blends, compositions of blends and variations thereof. The polymer may be in true solution, saturated, or suspended as particles or supersaturated in the beneficial agent. The polymer can be biocompatible, or biodegradable. For purpose of illustration and not limitation, the polymeric material may include, but is not limited to, poly(D-lactic acid) (PDLA), poly(D,L-lactic acid) (PDLLA), poly(iodinated desamino tyrosyl-tyrosine ethyl ester) carbonate, poly(lactic-co-glycolic acid) (PLGA), salicylate based polymer, semicrystalline polylactide, phosphorylcholine, polycaprolactone (PCL), poly-D,L-lactic acid, poly-L-lactic acid, poly(lactideco-glycolide), poly(hydroxybutyrate), poly(hydroxybutyrate-co-valerate), polydioxanone (PDS), polyorthoester, polyanhydride, poly(glycolic acid), poly(glycolic acid-co-trimethylene carbonate), polyphosphoester, polyphosphoester urethane, poly(amino acids), cyanoacrylates, poly(trimethylene carbonate), poly(iminocarbonate), polyalkylene oxalates, polyphosphazenes, polyiminocarbonates, and aliphatic polycarbonates, fibrin, fibrinogen, cellulose, starch, collagen, polyurethane including polycarbonate urethanes, polyethylene, polyethylene terephthalate, ethylene vinyl acetate, ethylene vinyl alcohol, silicone including polysiloxanes and substituted polysiloxanes, polyethylene oxide, polybutylene terephthalate-co-PEG, PCL-co-PEG, PLA-co-PEG, PLLA-co-PCL, polyacrylates, polyvinyl pyrrolidone, polyacrylamide, and combinations thereof. Non-limiting examples of other suitable polymers include thermoplastic elastomers in general, polyolefin elastomers, EPDM rubbers and polyamide elastomers, and biostable plastic material including acrylic polymers, and its derivatives, nylon, polyesters and expoxies. In some embodiments, the stent may include one or more coatings, with materials like poly(D,L-lactic acid) (PDLLA). These materials are merely examples, however, and should not be seen as limiting the scope of the invention.

[0092] Stent elements may comprise various shapes and configurations. Some or all of the stent elements may comprise closed-cell structures formed by intersecting struts. Closed-cell structures may comprise diamond, rhombus, rhomboid, trapezium, kite, square, rectangular, parallelogrammatic, triangular, pentagonal, hexagonal, heptagonal, octagonal, clover, lobular, circular, elliptical, and/or ovoid geometries. Closed-cells may also comprise slotted shapes such as H-shaped slots, I-shaped slots, J-shaped slots, and the like. Additionally or alternatively, stent may comprise open cell structures such as spiral structures, serpentine structures, zigzags structures, etc. Strut intersections may form pointed, perpendicular, rounded, bullnosed, flat, beveled, and/or chamfered cell corners. In an embodiment, stent may comprise multiple different cells having different cell shapes, orientations, and/or sizes. In an embodiment, stent elements may comprise a plurality of diamond or rhombus shaped closed cells longer in a longitudinal direction than in a radial direction when in an unexpanded state. The stent elements may also comprise a plurality of diamond or rhombus shaped closed cells longer in a radial direction than in a longitudinal direction in the expanded state.

[0093] One embodiment of a stent pattern is shown in shown in FIGS. 3A-3F. The stent elements 301 have a diamond or rhombus shaped closed-cell pattern. Elements 301 comprise intermixed diamond or rhombus shaped closed cells 304, 305. Diamond or rhombus shaped cells 304 may be aligned in the longitudinal and/or the circumferential directions in a repeating pattern. Similarly, diamond or rhombus shaped cells 305 may be aligned in the longitudinal and/or the circumferential directions in a repeating pattern. Additionally or alternatively, diamond or rhombus shaped cells 304 and diamond or rhombus shaped cells 305 may be helically aligned in an alternating pattern. In an embodiment, diamond or rhombus shaped cells 304 and diamond or rhombus shaped cells 305 are circumferentially offset. Additionally, diamond or rhombus shaped cells 305 may be formed at a central location between four adjacent diamond or rhombus shaped cells 304. The width and/or the height of struts 306 between two corners of longitudinally aligned diamond or rhombus shaped cells 304 may be larger or smaller than the width and/or height of struts 307 between two corners of longitudinally aligned diamond shaped cells 305.

[0094] FIGS. 4A-4D show various embodiments stent patterns with diamond or rhombus shaped closed-cell patterns. Diamond or rhombus shaped cells 404 may have rounded corners 405. In various embodiments diamond or rhombus shaped cells 404 may comprise circular keyhole shaped corners 406.

[0095] Unique characteristics of the scaffold patterns may include wide and/or thick struts and closed-cell structure designed for maximal strength without appreciable axial or bending flexibility (unlike metal stents). Thick and rigid scaffolds may be deployed oversized so as to overcome venous elastic recoil and anatomic compression, and remain securely imbedded within their venous target. Their high radial force, combined with the compressive force of the vein in which they are implanted, serves to specifically resist dislodgement and migration.

[0096] One embodiment of a stent pattern is shown in shown in FIGS. 5A-5D. The stent elements 501 have a diamond or rhombus shaped closed-cell pattern. Elements 501 comprise diamond or rhombus shaped closed cells 504. Elements 501 may comprise wide struts of 425 microns or larger. Elements 501 may similarly comprise thick struts of 425 microns or larger. In an embodiment, elements 501 comprise struts with a width 508 and/or thickness 509 of approximately 250 microns or more, 275 microns or more, 300 microns or more, 325 microns or more, 350 microns or more, 375 microns or more, 400 microns or more, 425 microns or more, 450 microns or more, 475 microns or more, 500 microns or more, 525 microns or more, or 550 microns or more. The width and/or the height of struts between two corners of diamond or rhombus shaped cells 504 may be larger or smaller than the width and/or height of struts forming the sides of diamond or rhombus shaped cells 504.

[0097] FIGS. 6A-6F show finite element analysis (FEA) of a bioresorbable venous stent showing thick struts than can withstand the stress of crimping. The stress scale is shown at the left. FIGS. 5A-5F show progressive crimping of a single cell 604. Note the maximal stress of 156 mises even when fully crimped (FIG. 6F) demonstrates that the device can be effectively crimped without undue strain or fracture.

[0098] FIGS. 7A-7E show deployment of a segmented, rigid, absorbable scaffold in the right porcine iliofemoral vein. FIG. 7A shows a pre-procedure venogram via direct injection into the right iliofemoral vein. Device advancement is seen in FIG. 7B. The two segments of the device are located between the balloon markers 701. FIG. 7C shows device deployment via balloon inflation 702. FIG. 7D shows a fully deployed device; note the slight dilatation of the venous wall provided by the two scaffolds 703. FIG. 7E is a magnified view of the image in 7D.

[0099] The device described herein may include incorporation of a therapeutic drug intended to prevent or attenuate pathologic consequences of intraluminal intervention such as inflammation, cell dysfunction, cell activation, cell proliferation, neointimal formation, thickening, late atherosclerotic change and/or thrombosis. Any suitable therapeutic agent (or “drug”) may be incorporated into, coated on, or otherwise attached to the stent, in various embodiments. Examples of such therapeutic agents include, but are not limited to, antithrombotics, anticoagulants, antiplatelet agents, anti-lipid agents, thrombolytics, antiproliferatives, anti-inflammatories, agents that inhibit hyperplasia, smooth muscle cell inhibitors, antibiotics, growth factor inhibitors, cell adhesion inhibitors, cell adhesion promoters, antimitotics, antifibrins, antioxidants, anti-neoplastics, agents that promote endothelial cell recovery, matrix metalloproteinase inhibitors, anti-metabolites, antiallergic substances, viral vectors, nucleic acids, monoclonal antibodies, inhibitors of tyrosine kinase, antisense compounds, oligonucleotides, cell permeation enhancers, hypoglycemic agents, hypolipidemic agents, proteins, nucleic acids, agents useful for erythropoiesis stimulation, angiogenesis agents, anti-ulcer/anti-reflux agents, and anti-nauseants/anti-emetics, PPAR alpha agonists such as fenofibrate, PPAR-gamma agonists selected such as rosiglitazaone and pioglitazone, sodium heparin, LMW heparins, heparoids, hirudin, argatroban, forskolin, vapriprost, prostacyclin and prostacylin analogues, dextran, D-phe-pro-arg-chloromethylketone (synthetic anti-thrombin), glycoprotein IIb/IIIa (platelet membrane receptor antagonist antibody), recombinant hirudin, thrombin inhibitors, indomethacin, phenyl salicylate, beta-estradiol, vinblastine, ABT-627 (astrasentan), testosterone, progesterone, paclitaxel, methotrexate, fotemusine, RPR-101511A, cyclosporine A, vincristine, carvediol, vindesine, dipyridamole, methotrexate, folic acid, thrombospondin mimetics, estradiol, dexamethasone, metrizamide, iopamidol, iohexol, iopromide, iobitridol, iomeprol, iopentol, ioversol, ioxilan, iodixanol, and iotrolan, antisense compounds, inhibitors of smooth muscle cell proliferation, lipid-lowering agents, radiopaque agents, antineoplastics, HMG CoA reductase inhibitors such as lovastatin, atorvastatin, simvastatin, pravastatin, cerivastatin and fluvastatin, and combinations thereof

[0100] Examples of antithrombotics, anticoagulants, antiplatelet agents, and thrombolytics include, but are not limited to, sodium heparin, unfractionated heparin, low molecular weight heparins, such as dalteparin, enoxaparin, nadroparin, reviparin, ardoparin and certaparin, heparinoids, hirudin, argatroban, forskolin, vapriprost, prostacyclin and prostacylin analogues, dextran, D-phe-pro-arg-chloromethylketone (synthetic antithrombin), dipyridamole, glycoprotein IIb/IIIa (platelet membrane receptor antagonist antibody), recombinant hirudin, and thrombin inhibitors such as bivalirudin, thrombin inhibitors, and thrombolytic agents, such as urokinase, recombinant urokinase, pro-urokinase, tissue plasminogen activator, ateplase and tenecteplase.

[0101] Examples of cytostatic or antiproliferative agents include, but are not limited to, rapamycin and its analogs, including everolimus, zotarolimus, tacrolimus, novolimus, and pimecrolimus, angiopeptin, angiotensin converting enzyme inhibitors, such as captopril, cilazapril or lisinopril, calcium channel blockers, such as nifedipine, amlodipine, cilnidipine, lercanidipine, benidipine, trifluperazine, diltiazem and verapamil, fibroblast growth factor antagonists, fish oil (omega 3-fatty acid), histamine antagonists, lovastatin, topoisomerase inhibitors, such as etoposide and topotecan, as well as antiestrogens such as tamoxifen.

[0102] Examples of anti-inflammatory agents include, but are not limited to, colchicine and glucocorticoids, such as betamethasone, cortisone, dexamethasone, budesonide, prednisolone, methylprednisolone and hydrocortisone. Non-steroidal anti-inflammatory agents include, but are not limited to, flurbiprofen, ibuprofen, ketoprofen, fenoprofen, naproxen, diclofenac, diflunisal, acetominophen, indomethacin, sulindac, etodolac, diclofenac, ketorolac, meclofenamic acid, piroxicam and phenylbutazone.

[0103] Examples of antineoplastic agents include, but are not limited to, alkylating agents including altretamine, bendamucine, carboplatin, carmustine, cisplatin, cyclophosphamide, fotemustine, ifosfamide, lomustine, nimustine, prednimustine, and treosulfin, antimitotics, including vincristine, vinblastine, paclitaxel, docetaxel, antimetabolites including methotrexate, mercaptopurine, pentostatin, trimetrexate, gemcitabine, azathioprine, and fluorouracil, antibiotics, such as doxorubicin hydrochloride and mitomycin, and agents that promote endothelial cell recovery such as estradiol.

[0104] Antiallergic agents include, but are not limited to, permirolast potassium nitroprusside, phosphodiesterase inhibitors, prostaglandin inhibitors, suramin, serotonin blockers, steroids, thioprotease inhibitors, triazolopyrimidine, and nitric oxide.

[0105] The beneficial agent may include a solvent. The solvent may be any single solvent or a combination of solvents. For purpose of illustration and not limitation, examples of suitable solvents include water, aliphatic hydrocarbons, aromatic hydrocarbons, alcohols, ketones, dimethyl sulfoxide, tetrahydrofuran, dihydrofuran, dimethylacetamide, acetates, and combinations thereof

[0106] Stents may be manufactured using an additive or a subtractive. In any of the described embodiments, stents or stent elements may be manufactured as a sheet and wrapped into cylindrical form. Alternatively, stents or stent elements may be manufactured in cylindrical form using an additive manufacturing process. In an embodiment, stents maybe formed by extruding a material into a cylindrical tubing. In some embodiments, a longer stent element, may be formed during the manufacturing process and then cut into smaller stent elements/elements to provide a multi-element stent. In an embodiment, stent tubing may be laser cut with a pattern to form a stent element.

[0107] Referring now to FIG. 8, in one embodiment, stents may be manufactured using a micro-stereolithography system 800 (or “3D printing system”). Several examples of currently available systems that might be used in various embodiments include, but are not limited to: MakiBox A6, Makible Limited, Hong Kong; CubeX, 3D Systems, Inc., Circle Rock Hill, S.C.; and 3D-Bioplotter, (EnvisionTEC GmbH, Gladbeck, Germany).

[0108] The micro-stereolithography system may include an illuminator, a dynamic pattern generator, an image-former and a Z-stage. The illuminator may include a light source, a filter, an electric shutter, a collimating lens and a reflecting mirror that projects a uniformly intense light on a digital mirror device (DMD), which generates a dynamic mask. FIG. 8 shows some of these components of one embodiment of the micro-stereolithography system 800, including a DMD board, Z-stage, lamp, platform, resin vat and an objective lens. The details of 3D printing/micro-stereolithography systems and other additive manufacturing systems will not be described here, since they are well known in the art. However, according to various embodiments, any additive manufacturing system or process, whether currently known or hereafter developed, may potentially be used to fabricate stents within the scope of the present invention. In other words, the scope of the invention is not limited to any particular additive manufacturing system or process.

[0109] In one embodiment, the system 800 may be configured to fabricate stents using dynamic mask projection micro-stereolithography. In one embodiment, the fabrication method may include first producing 3D microstructural scaffolds by slicing a 3D model with a computer program and solidifying and stacking images layer by layer in the system. In one embodiment, the reflecting mirror of the system is used to project a uniformly intense light on the DMD, which generates a dynamic mask. The dynamic pattern generator creates an image of the sliced section of the fabrication model by producing a black-and-white region similar to the mask. Finally, to stack the images, a resolution Z-stage moves up and down to refresh the resin surface for the next curing. The Z-stage build subsystem, in one embodiment, has a resolution of about 100 nm and includes a platform for attaching a substrate, a vat for containing the polymer liquid solution, and a hot plate for controlling the temperature of the solution. The Z-stage makes a new solution surface with the desired layer thickness by moving downward deeply, moving upward to the predetermined position, and then waiting for a certain time for the solution to be evenly distributed.

[0110] Because the device is comprised of fully bioresorbable material, it slowly begins to weaken and dissolve soon after being subjected to a warm, biologically active environment. The device is designed such that its rigidity is slowly attenuated as its structural polymer is unlinked and metabolized. As the device weakens, its effect on the venous wall is slowly released. Eventually, the device ceases to exert any radial effect on its host vein thus completely removing any pathologic stimuli for neointimal hyperplasia formation, ongoing thickening and maladaptation. The lack of continuous stimulation by an intravascular foreign body allows the vessel to re-enter a quiescent, patent state until such time that further plaque might be generated by its host.

[0111] To demonstrate the feasibility of the device described herein, an endovascular device consisting of two, closely spaced, polylactide-based, balloon-expandable scaffolds of ˜10 mm length crimped onto a single delivery balloon was created (FIG. 9). An experimental domestic farm pig was induced with general anesthesia, intubation and mechanical ventilation. The jugular vein was surgically exposed with the animal in dorsal recumbency. A sheath was inserted and advanced through the vena cava to the right femoral vein under fluoroscopic control. Heparin was administered to achieve an activated clotting time >300 s. The venous scaffold device was deployed into the right femoral vein using balloon inflation necessary to achieve complete wall apposition. Intraluminal scaffold imaging was performed using Optimal Coherence Tomography. The images revealed successful delivery of the device, close apposition of the struts to the venous wall and wide patency of the vein (FIG. 10). FIG. 10 shows the close apposition of the struts to the venous wall and wide patency of the vein.

[0112] Although particular embodiments have been shown and described, they are not intended to limit the invention. Various changes and modifications may be made to any of the embodiments, without departing from the spirit and scope of the invention. The invention is intended to cover alternatives, modifications, and equivalents.