Nanoporous stents with enhanced cellular adhesion and reduced neointimal formation

• US 9,770,349 B2
• Filed: 05/24/2007
• Issued: 09/26/2017
• Est. Priority Date: 11/13/2002
• Status: Active Grant

• Current Assignee: University of Virginia Patent Foundation (University of Virginia)
• Original Assignee: University of Virginia Patent Foundation (University of Virginia)
• Inventors: Owens, Gary, Lye, Whye-Kei, Reed, Michael, Spradlin, Joshua, Wamhoff, Brian, Hudson, Matthew, Looi, Kareen
• Primary Examiner(s): PREBILIC, PAUL B
• Application Number:
  US11/753,134
• Publication Number:
  US 20080086198A1
• Time in Patent Office: 3,778 Days
• Field of Search: 623 115, 623 142- 148
• CPC Class Codes: A61F 2/82 Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents stent-grafts for tubular structures of the body other than blood vessels A61F2/04; stent-grafts for blood vessels A61F2/07; instruments specially adapted for placement or removal of stents or stent-grafts A61F2/95; for closing wounds, or holding wounds closed A61B17/04 - A61B17/115; dilators A61M29/00
• CPC Class Codes: A61F 2/91 made from perforated sheet material or tubes, e.g. perforated by laser cuts or etched holes
• CPC Class Codes: A61F 2240/001 Designing or manufacturing processes
• CPC Class Codes: A61F 2250/0058 Additional features; Implant or prostheses properties not otherwise provided for

Abstract

The present invention relates generally to medical devices containing nanoporous surfaces and methods for making same. More specifically, the invention relates to implantable vascular stents or other biomedical devices having at least one dealloyed nanoporous layer that promotes improved cellular adhesion properties that promote healing and long term biocompatibility. In the case of stents, the nanoporous layer promotes re-endothelialization at sites of stent implantation vasculature, improves overall healing, and reduces inflammation and intimal disease progression. The nanoporous layer may be optionally loaded with one or more therapeutic agent to further improve the function of the implanted stent and further augment clinical efficacy.

Claims

1. A stent for insertion into a body, the stent comprising a metal stent having a dealloyed porous surface, wherein the stent with only the porous surface and devoid of a therapeutic agent exhibits reduced neointimal formation compared to a bare metal stent having the same configuration as the metal stent and lacking the porous surface.

2. The stent for insertion into a body as in claim 1, wherein the porous surface is a nanoporous surface with an average pore diameter of less than 200 nm.

3. The stent for insertion into a body as in claim 1, wherein the dealloyed surface is a nanoporous surface with an average pore diameter of less than 200 nm.

4. The stent for insertion into a body as in claim 1, wherein the stent is a coronary stent.

5. The stent for insertion into a body as in claim 1, wherein the stent further comprises a biodegradable coating bonded to the porous surface.

6. The stent for insertion into a body as in claim 1, wherein the stent exhibits a reduced percentage area of stenosis compared to the same bare metal stent lacking the porous surface.

7. The stent for insertion into a body as in claim 1, wherein the stent lacks an elutable therapeutic agent.

8. The stent for insertion into a body as in claim 3, wherein the nanoporous surface contains at least one therapeutic agent.

9. The stent for insertion into a body as in claim 8, wherein the at least one therapeutic agent is selected from a group consisting of:

actinomycin-D, batimistat, c-myc antisense, dexamethasone, paclitaxel, taxanes, sirolimus, tacrolimus, everolimus, unfractionated heparin, low-molecular weight heparin, enoxaprin, bivalirudin, tyrosine kinase inhibitors, imatinib mesylate, wortmannin, PDGF inhibitors, AG1295 (6,7-Dimethyl-2-phenylquinoxaline), rho kinase inhibitors, Y27632 ((+)-(R)-trans-4-(1-aminoethyl)-N-(4-pyridyl)cyclohexanecarboxamide dihydrochloride), calcium channel blockers, sphingosine phosphate inhibitors, amlodipine, nifedipine, ACE inhibitors, synthetic polysaccharides, ticlopinin, dipyridamole, clopidogrel, fondaparinux, streptokinase, urokinase, r-urokinase, r-prourokinase, rt-PA, APSAC (anisoylated plasminogen streptokinase activator complex), TNK-rt-PA, reteplase, alteplase, monteplase, lanoplase, pamiteplase, staphylokinase, abciximab, tirofiban, orbofiban, xemilofiban, sibrafiban, roxifiban, ABT-578, CCI-779, biolimus-A9, temsirolimus, anti-CD34 antibodies, mycophenolic acid, Vitamin E, omega-3 fatty acids, tempamine, docetaxel, an agent for altering cytochrome P450 function, cyclosporine, an azole antifungal agent, itraconazole, ketoconazole, a macrolide antibiotic, clarithromycin, erythromycin, troleandomycin, an non-nucleoside reverse transcriptase inhibitor, delavirdine, a protease inhibitor, indinavir, ritonavir, saquinavir, ritonavir, grapefruit juice extract, mifepristone, nefazodone, an anti-restenosis agent, an anti-thrombogenic agent, an antibiotic, an anti-platelet agent, an anti-clotting agent, an anti-inflammatory agent, an anti-neoplastic agent, a chelating agent, penicillamine, triethylene tetramine dihydrochloride, EDTA, DMSA (succimer), deferoxamine mesylate, a radiocontrast agent, a radio-isotope, a prodrug, antibody fragments, antibodies, live cells, therapeutic drug delivery microspheres, drug delivery microbeads, gene therapy agents, viral vectors and plasmid DNA vectors.

10. The stent for insertion into a body as in claim 2, wherein the average pore diameter is less than about 5 nm.

11. The stent for insertion into a body as in claim 3, wherein the average pore diameter is less than about 5 nm.