Claims for Patent: 9,237,945

Summary for Patent: 9,237,945

Title:	Bioerodible wraps and uses therefor
Abstract:	A tubular tissue graft device is provided comprising a tubular tissue and a restrictive fiber matrix of a bioerodible polymer about a circumference of the tubular tissue. The matrix may be electrospun onto the tubular tissue. In one embodiment, the tubular tissue is from a vein, such as a saphenous vein, useful as an arterial graft, for example and without limitation, in a coronary artery bypass procedure. Also provided is method of preparing a tubular graft comprising depositing a fiber matrix of a bioerodible polymer about a perimeter of a tubular tissue to produce a tubular tissue graft device. A cardiac bypass method comprising bypassing a coronary artery with a tubular tissue graft device comprising a vein and a restrictive fiber matrix of a bioerodible polymer about a circumference of the vein also is provided.
Inventor(s):	El-Kurdl; Mohammed S. (Pittsburgh, PA), Hong; Yi (Pittsburgh, PA), Soletti; Lorenzo (Pittsburgh, PA), Stankus; John J. (Campbell, CA), Vorp; David A. (Pittsburgh, PA), Wagner; William R. (Pittsburgh, PA)
Assignee:	University of Pittsburgh--Of the Commonwealth System of Higher Education (Pittsburgh, PA)
Application Number:	12/022,430
Patent Claims:	1. A tubular tissue graft device comprising: a living tubular tissue structure having a wall surrounding a lumen, the wall having an outer surface comprising a series of non-circular cross-sections varying at least in part over a portion of the length of the living tubular tissue structure; and an electrospun deposition coating formed of one or more bioerodible polymer fibers oriented circumferentially about the outer surface and along a portion of the length of the living tubular tissue structure, wherein the coating forms a restrictive fiber matrix with inherent anisotropy on the series of non-circular cross-sections that compose the outer surface of the living tubular tissue structure. 2. The device of claim 1, wherein the living tubular tissue structure is venous. 3. The device of claim 2, wherein the venous living tubular tissue structure is obtained from a saphenous vein. 4. The device of claim 1, wherein the one or more bioerodible polymer fibers comprise a polymer comprising ester and urethane linkages. 5. The device of claim 4, wherein the polymer comprising ester and urethane linkages comprises a poly(ester urethane)urea. 6. The device of claim 1, wherein the living tubular tissue structure is obtained from an artery, urethra, intestine, esophagus, ureter, trachea, bronchi, and fallopian tube, or a combination thereof. 7. The device of claim 1, wherein the one or more bioerodible polymer fibers comprise a polymer derived from an alpha-hydroxy acid, a polylactide, a poly(lactide-co-glycolide), a poly(L-lactide-co-caprolactone), a polyglycolic acid, a poly(dl-lactide-co-glycolide), a poly(1-lactide-co-dl-lactide), a polymer comprising a lactone monomer, a polycaprolactone, a polymer comprising carbonate linkages, a polycarbonate, a polyglyconate, a poly(glycolide-co-trimethylene carbonate), a poly(glycolide-co-trimethylene carbonate-co-dioxanone), a polymer comprising urethane linkages, a polyurethane, a poly(ester urethane) urea, a poly(ester urethane) urea elastomer, a polymer comprising ester linkages, a polyalkanoate, a polyhydroxybutyrate, a polyhydroxyvalerate, a polydioxanone, a polygalactin, a natural polymer, chitosan, collagen, elastin, alginate, cellulose, hyaluronic acid, gelatin, or a combination thereof. 8. The device of claim 1, wherein the one or more bioerodible polymer fibers comprise one or more polymers derived from an alpha-hydroxy acid. 9. The device of claim 8, wherein the one or more polymers derived from an alpha-hydroxy acid comprise a polylactide, a poly(lactide-co-glycolide), a poly(L-lactide-co-caprolactone), a polyglycolic acid, a poly(dl-lactide-co-glycolide), a poly(1-lactide-co-dl-lactide), or a combination thereof. 10. The device of claim 1, wherein the one or more bioerodible polymer fibers comprise one or more polymers comprising a lactone monomer. 11. The device of claim 10, wherein the one or more polymers comprising a lactone monomer comprise polycaprolactone. 12. The device of claim 1, wherein the one or more bioerodible polymer fibers comprise one or more polymers comprising carbonate linkages. 13. The device of claim 12, wherein the one or more polymers comprising carbonate linkages comprise polycarbonate, polyglyconate, poly(glycolide-co-trimethylene carbonate), poly(glycolide-co-trimethylene carbonate-co-dioxanone), or a combination thereof. 14. The device of claim 1, wherein the one or more bioerodible polymer fibers comprise one or more polymers comprising urethane linkages. 15. The device of claim 14, wherein the one or more polymers comprising urethane linkages comprise a polyurethane, a poly(ester urethane) urea elastomer, or a combination thereof. 16. The device of claim 15, wherein the one or more polymers comprising urethane linkages comprise the poly(ester urethane) urea elastomer. 17. The device of claim 16, wherein the one or more bioerodible polymer fibers further comprise collagen. 18. The device of claim 17, wherein the restrictive fiber matrix comprises from about 25% wt. to about 75% wt. collagen. 19. The device of claim 17, wherein one or more bioerodible polymer fibers further comprise elastin. 20. The device of claim 19, wherein the restrictive fiber matrix comprises from about 25% wt. to about 75% wt. of a mixture of collagen and elastin. 21. The device of claim 19, wherein the elastin and the collagen are present in the restrictive fiber matrix in approximately equal amounts. 22. The device of claim 1, wherein the one or more bioerodible polymer fibers comprise ester linkages. 23. The device of claim 22, wherein the one or more bioerodible polymer fibers comprising ester linkages comprise a polyalkanoate. 24. The device of claim 23, wherein the polyalkanoate comprises a polyhydroxybutyrate, polyhydroxyvalerate, and polydioxanone, or a combination thereof. 25. The device of claim 22, wherein the one or more bioerodible polymer fibers comprising ester linkages comprise a polygalactin. 26. The device of claim 1, wherein the one or more bioerodible polymer fibers comprise one or more natural polymers. 27. The device of claim 26, wherein the one or more natural polymers comprise chitosan, collagen, elastin, alginate, cellulose, polyalkanoates, hyaluronic acid, gelatin, or a combination thereof. 28. The device of claim 1, wherein the one or more bioerodible polymer fibers comprise collagen. 29. The device of claim 28, wherein the one or more bioerodible polymer fibers further comprise elastin. 30. The device of claim 28, wherein the restrictive fiber matrix bioerodes in situ over a time period ranging from 12 hours to two weeks. 31. The device of claim 1, further comprising one or more cells, active agents, or a combination thereof, associated with the restrictive fiber matrix. 32. The device of claim 31, comprising the one or more cells that are stem cells, progenitor (precursor) cells, smooth muscle cells, skeletal myoblasts, myocardial cells, endothelial cells, endothelial progenitor cells, bone-marrow derived mesenchymal cells, genetically modified cells, or a combination thereof. 33. The device of claim 31, comprising the one or more active agents that comprise a growth factor. 34. The device of claim 33, wherein the growth factor comprises basic fibroblast growth factor (bFGF), acidic fibroblast growth factor (aFGF), vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF), insulin-like growth factors (IGF), transforming growth factor-beta pleiotrophin protein, midkine protein, IGF-1, or a combination thereof. 35. The device of claim 31 further comprising the one or more active agents that comprise a drug. 36. The device of claim 35, wherein the drug comprises a non-steroidal anti-inflammatory drug, an antibiotic, an anticlotting factor, an immunosuppressant, a glucocorticoid, a drug acting on an immunophilin, an interferon, a TNF binding proteins, a taxane, a statin, and a nitric oxide donor or precursor, or a combination thereof. 37. The device of claim 35, wherein the drug comprises an NSAID, salicylic acid, indomethacin, sodium indomethacin trihydrate, salicylamide, naproxen, colchicine, fenoprofen, sulindac, diflunisal, diclofenac, indoprofen sodium salicylamide, antiinflammatory cytokines, antiinflammatory proteins, steroidal anti-inflammatory agents, heparin, Pebac, enoxaprin, aspirin, hirudin, plavix, bivalirudin, prasugrel, idraparinux, warfarin, coumadin, clopidogrel, PPACK, GGACK, tissue plasminogen activator, urokinase, streptokinase, a glucocorticoid, hydrocortisone, betamethisone, dexamethasone, flumethasone, isoflupredone, methylpred-nisolone, prednisone, prednisolone, triamcinolone acetonide, an antiangiogenic, fluorouracil, paclitaxel, doxorubicin, cisplatin, methotrexate, cyclophosphamide, etoposide, pegaptanib, lucentis, tryptophanyl-tRNA synthetase, retaane, CA4P, AdPEDF, VEGF-TRAP-EYE, AG-103958, Avastin, JSM6427, TG100801, ATG3, OT-551, endostatin, thalidomide, becacizumab, neovastat, an antiproliferative, sirolimus, paclitaxel, perillyl alcohol, famesyl transferase inhibitors, FPTIII, L744, antiproliferative factor, Van 10/4, doxorubicin, 5-FU, Daunomycin, Mitomycin, dexamethasone, azathioprine, chlorambucil, cyclophosphamide, methotrexate, mofetil, vasoactive intestinal polypeptide, an antibody, a drug acting on immunophilins, cyclosporine, zotarolimus, everolimus, tacrolimus, sirolimus, an interferon, a TNF binding protein, a taxane, paclitaxel, docetaxel, a statin, atorvastatin, lovastatin, simvastatin, pravastatin, fluvastatin, rosuvastatin a nitric oxide donor or precursor, Angeli's Salt, L-Arginine, Free Base, Diethylamine NONOate, Diethylamine NONOate/AM, Glyco-SNAP-1, Glyco-SNAP-2, (O)--S-Nitroso-N-acetylpenicillamine, S-Nitrosoglutathione, NOC-5, NOC-7, NOC-9, NOC-12, NOC-18, NOR-1, NOR-3, SIN-1, Hydrochloride, Sodium Nitroprusside, Dihydrate, Spermine NONOate, Streptozotocin, an antibiotic, acyclovir, afloxacin, ampicillin, amphotericin B, atovaquone, azithromycin, ciprofloxacin, clarithromycin, clindamycin, clofazimine, dapsone, diclazaril, doxycycline, erythromycin, ethambutol, fluconazole, fluoroquinolones, foscarnet, ganciclovir, gentamicin, iatroconazole, isoniazid, ketoconazole, levofloxacin, lincomycin, miconazole, neomycin, norfloxacin, ofloxacin, paromomycin, penicillin, pentamidine, polymixin B, pyrazinamide, pyrimethamine, rifabutin, rifampin, sparfloxacin, streptomycin, sulfadiazine, tetracycline, tobramycin, trifluorouridine, trimethoprim sulphate, Zn-pyrithione, silver salts such as chloride, bromide, iodide and periodate, or a combination thereof. 38. A method of preparing a tubular tissue graft device, the method comprising: providing a living tubular tissue structure having a wall surrounding a lumen, the wall having an outer surface comprising a series of non-circular cross-sections varying at least in part over a portion of the length of the living tubular tissue structure; and electrospinning a deposition coating formed of one or more bioerodible polymer fibers oriented circumferentially about the outer surface and along a portion of the length of the living tubular tissue structure, wherein the coating forms a restrictive fiber matrix with inherent anisotropy on the series of non-circular cross-sections that compose the outer surface of the living tubular tissue structure. 39. The method of claim 38, wherein the living tubular tissue structure is obtained from a vein. 40. The method of claim 38, wherein the living tubular tissue structure is obtained from a portion of a saphenous vein. 41. The method of claim 38, wherein the one or more bioerodible polymer fibers comprise a polymer derived from an alpha-hydroxy acid, a polylactide, a poly(lactide-co-glycolide), a poly(L-lactide-co-caprolactone), a polyglycolic acid, a poly(dl-lactide-co-glycolide), a poly(1-lactide-co-dl-lactide), a polymer comprising a lactone monomer, a polycaprolactone, a polymer comprising carbonate linkages, a polycarbonate, a polyglyconate, a poly(glycolide-co-trimethylene carbonate), a poly(glycolide-co-trimethylene carbonate-co-dioxanone), a polymer comprising urethane linkages, a polyurethane, a poly(ester urethane) urea, a poly(ester urethane) urea elastomer, a polymer comprising ester linkages, a polyalkanoate, a polyhydroxybutyrate, a polyhydroxyvalerate, a polydioxanone, a polygalactin, a natural polymer, chitosan, collagen, elastin, alginate, cellulose, hyaluronic acid, and gelatin, or a combination thereof. 42. The method of claim 38, wherein the one or more bioerodible polymer fibers comprise a polymer comprising ester and urethane linkages. 43. The method of claim 42, wherein the polymer comprising ester and urethane linkages comprises a poly(ester urethane)urea. 44. The method of claim 38, wherein the living tubular tissue structure is obtained from an artery, urethra, intestine, esophagus, ureter, trachea, bronchi, fallopian tube, or a combination thereof. 45. The method of claim 38, wherein the one or more bioerodible polymer fibers comprise one or more polymers derived from an alpha-hydroxy acid. 46. The method of claim 45, wherein the one or more polymers derived from an alpha-hydroxy acid comprise a polylactide, a poly(lactide-co-glycolide), a poly(L-lactide-co-caprolactone), a polyglycolic acid, a poly(dl-lactide-co-glycolide), a poly(1-lactide-co-dl-lactide), or a combination thereof. 47. The method of claim 38, wherein the one or more bioerodible polymer fibers comprise one or more polymers comprising a lactone monomer. 48. The method of claim 47, wherein the one or more polymers comprising a lactone monomer comprise polycaprolactone. 49. The method of claim 38, wherein the one or more bioerodible polymer fibers comprise one or more polymers comprising carbonate linkages. 50. The method of claim 49, wherein the one or more polymers comprising carbonate linkages comprise polycarbonate, polyglyconate, poly(glycolide-co-trimethylene carbonate), poly(glycolide-co-trimethylene carbonate-co-dioxanone), or a combination thereof. 51. The method of claim 38, wherein the one or more bioerodible polymer fibers comprise one or more polymers comprising urethane linkages. 52. The method of claim 51, wherein the one or more polymers comprising urethane linkages comprise a polyurethane, a poly(ester urethane) urea elastomer, or a combination thereof. 53. The method of claim 52, wherein the one or more polymers comprising urethane linkages comprise the poly(ester urethane) urea elastomer. 54. The method of claim 53, wherein the one or more bioerodible polymer fibers further comprise collagen. 55. The method of claim 54, wherein the restrictive fiber matrix comprises from about 25% wt. to about 75% wt. collagen. 56. The method of claim 54, wherein one or more bioerodible polymer fibers further comprise elastin. 57. The method of claim 38, wherein the restrictive fiber matrix bioerodes in situ over a time period ranging from 12 hours to two weeks. 58. The method of claim 56, wherein the restrictive fiber matrix comprises from about 25% wt. to about 75% wt. of a mixture of collagen and elastin. 59. The method of claim 56, wherein the elastin and the collagen are present in the restrictive fiber matrix in approximately equal amounts. 60. The method of claim 38, wherein the one or more bioerodible polymer fibers comprise ester linkages. 61. The method of claim 60 wherein the one or more bioerodible polymer fibers comprising ester linkages comprise a polyalkanoate. 62. The method of claim 61, wherein the polyalkanoate comprises a polyhydroxybutyrate, polyhydroxyvalerate, polydioxanone, or a combination thereof. 63. The device of claim 60, wherein the one or more bioerodible polymer fibers comprising ester linkages comprise a polygalactin. 64. The method of claim 38, wherein the one or more bioerodible polymer fibers comprise one or more natural polymers. 65. The method of claim 64, wherein the one or more natural polymers comprise chitosan, collagen, elastin, alginate, cellulose, polyalkanoates, hyaluronic acid, gelatin, or a combination thereof. 66. The method of claim 38, wherein the one or more bioerodible polymer fibers comprise collagen. 67. The method of claim 66, wherein the one or more bioerodible polymer fibers further comprise elastin. 68. The method of claim 38, wherein the living tubular tissue structure is portion of a saphenous vein. 69. The method of claim 38, further comprising removing the living tubular tissue structure from a patient prior to electrospinning the deposition, and grafting the tubular tissue graft device into the patient after electrospinning the deposition. 70. The method of claim 38, further comprising associating one or more cells, active agents, or a combination thereof with the restrictive fiber matrix. 71. The method of claim 70, comprising associating the one or more cells comprising stem cells, progenitor (precursor) cells, smooth muscle cells, skeletal myoblasts, myocardial cells, endothelial cells, endothelial progenitor cells, bone-marrow derived mesenchymal cells, genetically modified cells, or a combination thereof with the restrictive fiber matrix. 72. The method of claim 70, comprising associating the one or more active agents that comprise a growth factor with the restrictive fiber matrix. 73. The method of claim 72, wherein the growth factor comprises basic fibroblast growth factor (bFGF), acidic fibroblast growth factor (aFGF), vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF), insulin-like growth factors (IGF), transforming growth factor-beta pleiotrophin protein, midkine protein, IGF-1, or a combination thereof. 74. The method of claim 70, comprising associating the one or more active agents that comprise a drug with the restrictive fiber matrix. 75. The method of claim 74, wherein the drug comprises a non-steroidal anti-inflammatory drug, an antibiotic, an anticlotting factor, an immunosuppressant, a glucocorticoid, a drug acting on an immunophilin, an interferon, a TNF binding proteins, a taxane, a statin, a nitric oxide donor or precursor, or a combination thereof. 76. The method of claim 74, wherein the comprises an NSAID, salicylic acid, indomethacin, sodium indomethacin trihydrate, salicylamide, naproxen, colchicine, fenoprofen, sulindac, diflunisal, diclofenac, indoprofen sodium salicylamide, antiinflammatory cytokines, antiinflammatory proteins, steroidal anti-inflammatory agents, heparin, Pebac, enoxaprin, aspirin, hirudin, plavix, bivalirudin, prasugrel, idraparinux, warfarin, coumadin, clopidogrel, PPACK, GGACK, tissue plasminogen activator, urokinase, streptokinase, a glucocorticoid, hydrocortisone, betamethisone, dexamethasone, flumethasone, isoflupredone, methylpred-nisolone, prednisone, prednisolone, triamcinolone acetonide, an antiangiogenic, fluorouracil, paclitaxel, doxorubicin, cisplatin, methotrexate, cyclophosphamide, etoposide, pegaptanib, lucentis, tryptophanyl-tRNA synthetase, retaane, CA4P, AdPEDF, VEGF-TRAP-EYE, AG-103958, Avastin, JSM6427, TG100801, ATG3, OT-551, endostatin, thalidomide, becacizumab, neovastat, an antiproliferative, sirolimus, paclitaxel, perillyl alcohol, farnesyl transferase inhibitors, FPTIII, L744, antiproliferative factor, Van 10/4, doxorubicin, 5-FU, Daunomycin, Mitomycin, dexamethasone, azathioprine, chlorambucil, cyclophosphamide, methotrexate, mofetil, vasoactive intestinal polypeptide, an antibody, a drug acting on immunophilins, cyclosporine, zotarolimus, everolimus, tacrolimus, sirolimus, an interferon, a TNF binding protein, a taxane, paclitaxel, docetaxel, a statin, atorvastatin, lovastatin, simvastatin, pravastatin, fluvastatin, rosuvastatin a nitric oxide donor or precursor, Angeli's Salt, L-Arginine, Free Base, Diethylamine NONOate, Diethylamine NONOate/AM, Glyco-SNAP-1, Glyco-SNAP-2, (.+-.)-S-Nitroso-N-acetylpenicillamine, S-Nitrosoglutathione, NOC-5, NOC-7, NOC-9, NOC-12, NOC-18, NOR-1, NOR-3, SIN-1, Hydrochloride, Sodium Nitroprusside, Dihydrate, Spermine NONOate, Streptozotocin, an antibiotic, acyclovir, afloxacin, ampicillin, amphotericin B, atovaquone, azithromycin, ciprofloxacin, clarithromycin, clindamycin, clofazimine, dapsone, diclazaril, doxycycline, erythromycin, ethambutol, fluconazole, fluoroquinolones, foscarnet, ganciclovir, gentamicin, iatroconazole, isoniazid, ketoconazole, levofloxacin, lincomycin, miconazole, neomycin, norfloxacin, ofloxacin, paromomycin, penicillin, pentamidine, polymixin B, pyrazinamide, pyrimethamine, rifabutin, rifampin, sparfloxacin, streptomycin, sulfadiazine, tetracycline, tobramycin, trifluorouridine, trimethoprim sulphate, Zn-pyrithione, and silver salts such as chloride, bromide, iodide, periodate, or a combination thereof. 77. A tubular tissue graft device comprising: a living tubular tissue structure having a wall surrounding a lumen, the wall having an outer surface comprising a series of non-circular cross-sections varying at least in part over a portion of the length of the living tubular tissue structure; and an electrospun deposition coating formed of bioerodible polymer fibers oriented circumferentially about the outer surface and along a portion of the length of the living tubular tissue structure, wherein the coating forms a restrictive fiber matrix with inherent anisotropy on the series of non-circular cross-sections that compose the outer surface of the living tubular tissue structure such that the fiber matrix limits the living tubular tissue structure from expanding beyond a predetermined maximum distension size for the living tubular tissue structure. 78. A method of preparing a tubular tissue graft device, the method comprising: providing a living tubular tissue structure having a wall surrounding a lumen, the wall having an outer surface comprising a series of non-circular cross-sections varying at least in part over a portion of the length of the living tubular tissue structure; and electrospinning a deposition coating formed of one or more bioerodible polymer fibers oriented circumferentially about the outer surface and along a portion of the length of the living tubular tissue structure by applying a potential difference between a deposition nozzle and a target where the target has a negative electrical potential relative to ground, wherein the coating forms a restrictive fiber matrix with inherent anisotropy on the series of non-circular cross-sections that compose the outer surface of the living tubular tissue structure. 79. The method of claim 78, wherein the negative electrical potential comprises a voltage between -2 Kv and -10 kV. 80. The method of claim 78, wherein the deposition nozzle is charged at an electrical potential having a voltage between +3 kV and +15 kV. 81. The method of claim 78, wherein the living tubular tissue structure is rotated at approximately 250 rpm during the electrospinning. 82. The method of claim 78, wherein the deposition nozzle is translated over the living tubular tissue structure between two ends of the living tubular tissue structure at approximately 8 centimeter per second during the electro spinning. 83. The method of claim 78 wherein electrospinning the deposition comprises expelling a polymer solution from the deposition nozzle at a flow rate of approximately 1.0 mL/hr.

Details for Patent 9,237,945

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Microbix Biosystems Inc.	KINLYTIC	urokinase	For Injection	021846	01/16/1978		2027-01-30
Genentech, Inc.	AVASTIN	bevacizumab	Injection	125085	02/26/2004		2027-01-30
Genentech, Inc.	LUCENTIS	ranibizumab	Injection	125156	06/30/2006		2027-01-30