Methods And Compositions For Enhacing Vascular Access

• US 20080119946A1
• Filed: 12/06/2005
• Published: 05/22/2008
• Est. Priority Date: 12/08/2004
• Status: Abandoned Application

• Current Assignee: Shire Regenerative Medicine Incorporated (Shire plc)
• Original Assignee: Shire Regenerative Medicine Incorporated (Shire plc)
• Inventors: Edelman, Elazer, Nugent, Helen Marie, Bollinger, Steve, Dalal, Anupam, Epperly, Scott
• Application Number:
  US11/792,350
• Publication Number:
  US 20080119946A1
• Time in Patent Office: Days
• US Class Current: 623/23.72
• CPC Class Codes: A61F 2310/00365 Proteins; Polypeptides; Degradation products thereof
• CPC Class Codes: A61L 27/3808 Endothelial cells
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 7/02 Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
• CPC Class Codes: A61P 7/04 Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/08 Vasodilators for multiple indications
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis

Abstract

Disclosed is an implantable material comprising a biocompatible matrix and cells which, when provided to a vascular access structure, can promote functionality generally. For example, implantable material of the present invention can enhance maturation of an arteriovenous native fistula as well as prolong the fistula in a mature, functional state suitable for dialysis. Additionally, the present invention can promote formation of a functional arteriovenous graft suitable for dialysis as well as promote formation of a functional peripheral bypass graft. Implantable material can be configured as a flexible planar form or a flowable composition with shape retaining properties suitable for implantation at, adjacent or in the vicinity of an anastomoses or arteriovenous graft. According to the methods disclosed herein, the implantable material is provided to an exterior surface of a blood vessel. Certain embodiments of the flexible planar form define a slot. The materials and methods of the present invention comprise cells, preferably endothelial cells or cells having an endothelial-like phenotype.

Claims

1. A method for treating a vascular access structure in a patient, the method comprising the step of locating at, adjacent or in the vicinity of the vascular access structure in said patient an implantable material comprising cells and a biocompatible matrix, wherein the implantable material is effective to promote functionality of said structure.

2. The method of claim 1 wherein the vascular access structure is an arteriovenous native fistula, an arteriovenous graft, or a venous catheter.

3. The method of claim 2 wherein the arteriovenous graft comprises a prosthetic bridge.

4. The method of claim 2 wherein the catheter is an indwelling dual lumen catheter.

5. The method of claim 1 wherein the vascular access structure is for dialysis.

6. The method of claim 2 wherein treating the arteriovenous fistula promotes repetitive cannulation.

7. The method of claim 1 wherein treating the vascular access structure promotes normal or near-normal blood flow through and downstream of the structure.

8. The method of claim 7 wherein blood flow is at a rate sufficient to prevent re-circulation during hemodialysis.

9. The method of claim 1 wherein treating the vascular access structure promotes normal or near-normal vessel diameter.

10. The method of claim 1 wherein treating the vascular access structure reduces flow recirculation during hemodialysis.

11. The method of claim 2 wherein treating the arteriovenous native fistula promotes clinical maturation sufficient to permit hemodialysis.

12. The method of claim 2 wherein the implantable material reduces delay in maturation of the arteriovenous native fistula.

13. The method of claim 2 wherein treating the arteriovenous graft promotes clinical stability sufficient to restore normal or near normal peripheral circulation.

14. The method of claim 2 wherein treating the indwelling dual lumen catheter promotes clinical stability sufficient to permit hemodialysis.

15. The method of claim 2 wherein the implantable material reduces the occurrence of revision in the patient.

16. An implantable material comprising cells and a biocompatible matrix suitable for use with the method of claim 1.

17. The implantable material of claim 16 wherein the cells are endothelial cells or cells having an endothelial-like phenotype.

18. The implantable material of claim 16 wherein the biocompatible matrix is a flexible planar material or a flowable composition.

19. The implantable material of claim 18 wherein the flexible planar material is configured for implantation at an anastomosis.

20. The implantable material of claim 19 wherein the material defines a slot.

21. The implantable material of claim 19 wherein the material is configured as in FIG. 1 or 2A.

22. The implantable material of claim 18 wherein the flowable composition is a shape-retaining composition.

70. The implantable material of claim 16 wherein the cells are selected from the group consisting of:

a confluent population of cells;

a near confluent population of cells;

a post confluent population of cells; and

cells which have a phenotype of any one of the foregoing population of cells.

71. The implantable material of claim 17 wherein the cells are selected from the group consisting of:

a confluent population of cells;

a near confluent population of cells;

a post confluent population of cells; and

cells which have a phenotype of any one of the foregoing population of cells.

23. A method for enhancing maturation of an arteriovenous fistula in a human, the method comprising the step of locating at, adjacent or in the vicinity of the fistula an implantable material comprising a biocompatible matrix and cells wherein the implantable material is effective to enhance maturation of the fistula.

24. The method of claim 23 wherein enhancing maturation is characterized by an ability to repetitively cannulate the fistula for dialysis.

25. The method of claim 23 wherein enhancing maturation is characterized by an ability to obtain sufficient blood flow during dialysis.

26. The method of claim 25 wherein sufficient blood flow comprises a rate of about 350 ml/min.

27. The method of claim 23 wherein the arteriovenous fistula is radiocephalic, brachiocephalic, or brachiobasilic.

28. The method of claim 23 wherein application of the biocompatible material to the arteriovenous fistula is preceded by or coincident with administration of a therapeutic agent.

29. The method of claim 23 wherein application of the biocompatible material to the arteriovenous fistula is preceded by physical dilatation.

40. An implantable material comprising cells and a biocompatible matrix suitable for use with the method of claim 23.

41. The implantable material of claim 40 wherein the cells are endothelial cells or cells having an endothelial-like phenotype.

42. The implantable material of claim 40 wherein the biocompatible matrix is a flexible planar material or a flowable composition.

43. The implantable material of claim 42 wherein the flexible planar material is configured for implantation at an anastomosis.

44. The implantable material of claim 43 wherein the material defines a slot.

45. The implantable material of claim 43 wherein the material is configured as in FIG. 1 or 2A.

46. The implantable material of claim 42 wherein the flowable composition is a shape-retaining composition

72. The implantable material of claim 40 wherein the cells are selected from the group consisting of:

a confluent population of cells;

a near confluent population of cells;

a post confluent population of cells; and

cells which have a phenotype of any one of the foregoing population of cells.

30. A method for preventing an arteriovenous fistula from failing to mature in a human, the method comprising the step of locating a biocompatible matrix comprising engrafted vascular endothelial cells at, adjacent or in the vicinity of the fistula in the human thereby to prevent a fistula from failing to mature.

31. The method of claim 30 wherein failing to mature is characterized by an inability to repetitively cannulate the fistula for dialysis.

32. The method of claim 30 wherein failing to mature is characterized by an inability to obtain sufficient blood flow during dialysis.

33. The method of claim 32 wherein the sufficient blood flow comprises a rate of about 350 ml/min.

34. The method of claim 30 wherein the arteriovenous fistula is radiocephalic, brachiocephalic, or brachiobasilic.

35. The method of claim 30 wherein application of the biocompatible material to the arteriovenous fistula is preceded by or coincident with administration of a therapeutic agent.

36. The method of claim 30 wherein application of the biocompatible material to the arteriovenous fistula is preceded by physical dilatation.

37. The method of claim 31 wherein the arteriovenous fistula can not be cannulated at least 2 months after creation.

38. The method of claim 31 wherein the arteriovenous fistula can not be cannulated at least 3 months after creation.

39. The method of claim 31 wherein the arteriovenous fistula can not be cannulated at least 4 months after creation.

47. A method of maintaining a blood flow rate of an arteriovenous graft, the method comprising the step of providing an implantable material comprising cells and a biocompatible matrix wherein said implantable material is disposed on an exterior surface of said arteriovenous graft at, adjacent or in the vicinity of a prosthetic bridge of a venous outflow region of said arteriovenous graft in an amount effective to maintain blood flow rate of the graft.

48. The method of claim 47 wherein the blood flow rate at the venous outflow region of said arteriovenous graft is substantially similar to the blood flow rate upstream of said outflow region;

or wherein the blood flow rate is sufficient to permit dialysis.

62. An implantable material comprising cells and a biocompatible matrix suitable for use with the method of claim 47.

63. The implantable material of claim 62 wherein the cells are endothelial cells or cells having an endothelial-like phenotype.

64. The implantable material of claim 62 wherein the biocompatible matrix is a flexible planar material or a flowable composition.

65. The implantable material of claim 64 wherein the flexible planar material is configured for implantation at, adjacent or in the vicinity of an anastomosis.

66. The implantable material of claim 64 wherein the flexible planar material is configured for implantation at, adjacent or in the vicinity of an arteriovenous graft.

67. The implantable material of claim 64 wherein the material defines a slot.

68. The implantable material of claim 64 wherein the material is configured as in FIG. 1 or 2A.

69. The implantable material of claim 64 wherein the flowable composition is a shape-retaining composition.

49. A method of maintaining normal blood flow of a peripheral bypass graft sufficient to maintain peripheral circulation, the method comprising the step of providing an implantable material comprising cells and a biocompatible matrix wherein said implantable material is disposed on an exterior surface of said bypass graft at, adjacent or in the vicinity of a prosthetic bridge in an amount effective to maintain blood flow rates of the bypass graft sufficient to maintain peripheral circulation.

50. The method of claim 49 wherein an inflow blood rate and an outflow blood rate are substantially similar.

56. The method of claim 49 wherein the providing step is performed as an interventional therapy following failure of a native or saphenous vein peripheral bypass.

51. A method of promoting tissue integration of a prosthetic bridge of an arteriovenous graft or a peripheral bypass graft, the method comprising the step of providing an implantable material comprising cells and a biocompatible matrix wherein said implantable material is disposed on an exterior surface of said arteriovenous graft or said peripheral bypass graft at, adjacent or in the vicinity of a prosthetic bridge in an amount effective to promote tissue integration of said bridge.

52. The method of claim 51 wherein said implantable material promotes smooth muscle cell proliferation or migration within or in the vicinity of an interior lumen surface of said prosthetic bridge.

53. The method of claim 51 wherein said implantable material promotes endothelial cell proliferation or migration within or in the vicinity of an interior lumen surface of said prosthetic bridge.

54. A method of preventing or reducing the incidence of dehiscence of an arteriovenous fistula or arteriovenous graft, the method comprising the step of providing an implantable material comprising cells and a biocompatible matrix wherein said implantable material is disposed on an exterior surface of said fistula or arteriovenous graft at, adjacent or in the vicinity of a prosthetic bridge of a venous outflow region of said arteriovenous graft in an amount effective to prevent or reduce the incidence of dehiscence.

55. The method of claim 54 wherein the providing step is performed as an interventional therapy following failure of a native arteriovenous fistula.

57. An implantable material comprising:

(a) cells; and

,

(b) a biocompatible matrix;

wherein said implantable material is disposed in the vicinity of, adjacent or contacting a prosthetic bridge; and

wherein said prosthetic bridge is situated at or near a venous outflow region of an arteriovenous graft or is situated at or near an outflow of a peripheral bypass graft.

73. The implantable material of claim 57 wherein the cells are selected from the group consisting of:

a confluent population of cells;

a near confluent population of cells;

a post confluent population of cells; and

cells which have a phenotype of any one of the foregoing population of cells.

58. A method of maintaining a blood pressure of an arteriovenous graft sufficient to permit dialysis, the method comprising the step of providing an implantable material comprising cells and a biocompatible matrix wherein said implantable material is disposed on an exterior surface of said arteriovenous graft at, adjacent or in the vicinity of a prosthetic bridge of a venous outflow region of said arteriovenous graft in an amount effective to maintain blood pressure sufficient to permit dialysis.

59. The method of claim 58 wherein the blood pressure at the venous outflow region of said arteriovenous graft is substantially similar to the blood pressure upstream of said outflow region.

60. The method of claim 58 wherein the prosthetic bridge is selected from the group consisting of:

saphenous vein;

bovine heterograft;

umbilical vein;

dacron;

PTFE;

ePTFE;

polyurethane;

bovine mesenteric vein; and

cryopreserved femoral vein allograft.

61. The method of claim 60 wherein the prosthetic bridge is ePTFE.