 intricate stent designs. The process from the apparatus results in the tubular member having a discrete pattern of exposed photosensitive material with the remaining areas having unexposed photosensitive resist.
The exposed tubular member is immersed in a resist developer for a specified period of time. The developer removes the relatively soft, uncured photosensitive resist polymer and leaves behind the cured photosensitive resist which mimics the stent pattern. Thereafter, excess developer is removed from the tubular member by rinsing with an appropriate solvent. At this time, the entire tubular member is incubated for a specified period of time, allowing the remaining photosensitive resist polymer to fully cure and bond to the surface of the processed tubular member.
The processed tubular member is then exposed to an electrochemical etching process, which removes uncovered metal from the tubular member, resulting in the final tubular member or stent configuration.
In an example of the laser/etching process, a tubular member is coated with a resist and placed in a rotatable collet fixture of a machine-controlled apparatus for positioning the tubular member relative to a laser. Then, according to the machine coded instructions, the tubing is rotated and moved longitudinally relative to the laser which is also machine controlled wherein the laser selectively removes the resistant coating on the tubular member by ablation. A stent pattern is formed on the surface of the tubular member that is created by a subsequent chemical etching process.
In an example of the direct laser method, a tubular member is placed in a collet fixture of a machine-controlled apparatus for positioning the tubular member relative to a laser. Then, according to the machine coded instructions, the tubing is rotated and moved longitudinally relative to the laser which is also machine controlled wherein the laser selectively ablates and removes metal forming the stent pattern.
The presence of a stent in a vessel tends to promote thrombus formation as blood flows through the vessel, which results in an acute blockage. In addition, as the outward facing surface of the stent in contact or engagement with the inner lining of the vessel, tissue irritation can exacerbate restenosis attributable to hyperplasia. The thrombosis and occlusion caused by the placement of the stent may be reduced or even eliminated by proper modification of the surface of the stent.
Surface modification of the stent to apply a desired coating such as iridium oxide or titanium nitrate may be achieved by vapor deposition or plasma deposition, or other conventional methods. Such modification may be used to give the stent a rough surface. Alternatively, the surface may be passivated only, by oxidation of the iridium for reduced immunoresponse and less throubogenicity. Other surface modification may include Ion Implantation process which forms a barrier to metal such as nickel to leach out.
In the evolution of stents, there have been developments in the field of stents coated with a layer of polymers. The polymeric materials are typically capable of absorbing and releasing therapeutic drugs. Examples of such stents are disclosed In U.S. Pat. No. 5,443,358 to Eury; U.S. Pat. No. 5,632,840 to Campbell; U.S. Pat. No. 5,843,172 to Yan; and U.S. Ser. No. 08/837,993, filed Apr. 15, 1997, by Yan.
Stents may be coated with one or more layers (coatings). The external surfaces and intratubular surfaces may have different coatings. The coatings may incorporate any desired substances including therapeutic substances, alone or in a carrier, so that the substances are released over time after implantation. The coatings usually employ polymers that include polycarboxylic acids; cellulosic polymers including cellulose acetate and cellulose nitrate; gelatin; polyvinylpyrrolidone; crosslinked polyvinylpyrrolidone; polyanhydrides including maleic anhydride polymers; polyamides; polyvinyl alcohols; copolymers of vinyl monomers such as EVA; polyvinyl ethers; polyvinyl aromatics; polyethylene oxides; polyesters including polyethylene terephthalate; polyacrylamides; polyethers; polyether sulfone; polycarbonate; polyalkylenes including polypropylene, polyethylene and high molecular weight polyethylene; halogenated polyalkylenes including polytetrafluoroethylene; polyurethanes; polyorthoesters; silicones; siloxane polymers; polylactic acid; polyglycolic acid; polycaprolactone; polyhydroxybutyrate valerate and blends and copolymers thereof; polypeptides; proteins including fibrin, collagen and derivatives thereof; glycosaminoglycans; polysaccharides such as celluloses, starches, dextrans, alginates and derivatives; hyaluronic acid; and squalene emulsions.
Therapeutic substances which can be delivered from stents include anti-thrombogenic agents such as heparin, heparin derivatives, urokinase, and PPack (dextrophenylalanine proline arginine chloromethylketone); anti-proliferative agents such as enoxaprin, angiopeptin, or monoclonal antibodies capable of blocking smooth muscle cell proliferation, hirudin, and acetylsalicylic acid; anti-inflammatory agents such as dexamethasone, prednisolone, corticosterone, budesonide, estrogen, sulfasalazine, and mesalamine; antineoplastic/antiproliferative/anti-miotic agents such as paclitaxel, 5-fluorouracil, cisplatin, vinblastine, vincristine, epothilones, endostatin, anglostatin and thymidine kinase inhibitors; anesthetic agents such as lidocaine, bupivacaine, and ropivacaine; anticoagulants such as D-Phe-Pro-Arg chloromethyl keton, an RGD peptide-containing compound, heparin, antithrombin compounds, platelet receptor antagonists, antithrombin anticodies, anti-platelet receptor antibodies, aspirin, prostaglandin inhibitors, platelet inhibitors and tick antiplatelet peptides; vascular cell growth prornotors such as growth factor inhibitors, growth factor receptor antagonists, transcriptional activators, and translational promotors; vascular cell growth inhibitors such as growth factor inhibitors, growth factor receptor antagonists, transcriptional repressors, translational repressors, replication inhibitors, inhibitory antibodies, antibodies directed against growth factors, bifunctional molecules consisting of a growth factor and a cytotoxin, bifunctional molecules consisting of an antibody and a cytotoxin; cholesterol-lowering agents; vasodilating agents; and agents which interfere with endogenous vascoactive mechanisms; anti-sense DNA and RNA; DNA coding for anti-sense RNA; tRNA or rRNA to replace defective or deficient endogenous molecules; angiogenic factors including growth factors such as acidic and basic fibroblast growth factors, vascular endothelial growth factor, epidermal growth factor, transforming growth factor α and β, platelet-derived endothelial growth factor, platelet-derived growth factor, tumor necrosis factor α, hepatocyte growth factor and insulin like growth factor; cell cycle inhibitors including CD inhibitors; thymidine kinase (“TK”) and other agents useful for interfering with cell proliferation; the family of bone morphogenic proteins (“BMP's”); and BMP-2, BMP-3, BMP-4, BMP-5, BMP-6 (Vgr-1), BMP-7 (OP-1), BMP-8, BMP-9, BMP-10, BMP-11, BMP-12, BMP-13, BMP-14, BMP-15, and BMP-16. Currently preferred BMP's are any of BMP-2, BMP-3, BMP BMP-5, BMP-6 and BMP. These dimeric proteins can be provided as homodimers, heterodimers, or combinations thereof, alone or together with other molecules. Alternatively or, in addition, molecules capable of inducing an upstream or downstream effect of a BMP can be provided. Such molecules include any of the “hedgehog” proteins, or the DNA's encoding them.
Stents or prostheses have been largely used in vascular structures including arteries and veins. Aside from vascular usage, other ducts or tracts of the human body in which a stent might be installed to maintain an open lumen include the tracheo-bronchial system, the biliary hepatic system, the esophageal bowel system, and the urinary tract. Many of the same requirements are found in these other endoluminal usages of stents.
Stents are used in many ways. For instance, stents have been used after atherectomy or standard balloon angioplasty to maintain acute and long-term patency of the vessel. Stents have also been used to overlie an aortic dissecting aneurysm, tack dissections to the vessel wall, eliminate the risk of occlusion caused by flaps resulting from the intimal tears associated with primary interventional procedure, or prevent elastic recoil of the vessel. Stents may be utilized in by-pass grafts as well, to maintain vessel patency. Stents can also be used to reinforce collapsing structures in the respiratory, biliary, urological, and other tracts.
Referring to FIG. 4, a diagram of ICA and Circle of Willis (CW) arteries is shown. The stents are suitable for placement in small vascular structures such as of the brain. The internal carotid artery (ICA) 117 supplying blood to arteries such as the middle cerebral artery (MCA), and Circle of Willis. Also, vertebral arteries (VA) supplying blood to basilar (BA) and intracranial arteries through Circle of Willis are shown. Ischemic disease is shown in VA, ICA, BA and MCA. Aneurysms are shown on CW and ICA.
Access to small occluded arteries of the brain to allow adequate blood flow (Ischemic) or repairing a ruptured aneurysm is a highly desirable objective for treating millions of people who suffer from stroke each year. One of the technical prerequisites for successful treatment in these respects is the availability of a stent, and related delivery system, which is sufficiently small and thin that it can navigate and be deployed in these tiny vessels without occluding or damaging the lumen