Method and implantable article for promoting endothelialization

• US 5,744,515 A
• Filed: 10/11/1996
• Issued: 04/28/1998
• Est. Priority Date: 05/26/1995
• Status: Expired due to Term

• Current Assignee: Arizona Board of Regents (University of Arizona)
• Original Assignee: BSI SA (Assicurazioni Generali SPA)
• Inventors: Clapper, David L.
• Primary Examiner(s): MERRIAM, ANDREW EDWIN
• Application Number:
  US08/729,537
• Time in Patent Office: 564 Days
• Field of Search: 523/113, 523/114, 424/423, 427/2.24, 514/8, 514/21, 623/1, 623/11
• US Class Current: 523/113
• CPC Class Codes: A61F 2/0077 Special surfaces of prostheses, e.g. for improving ingrowth A61F2/30767 takes precedence
• CPC Class Codes: A61F 2/06 Blood vessels
• CPC Class Codes: A61L 27/16 obtained by reactions only involving carbon-to-carbon unsaturated bonds
• CPC Class Codes: A61L 27/18 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
• CPC Class Codes: A61L 27/56 Porous materials, e.g. foams or sponges
• CPC Class Codes: C08L 27/18 Homopolymers or copolymers or tetrafluoroethene
• CPC Class Codes: C08L 67/02 Polyesters derived from dicarboxylic acids and dihydroxy compounds C08L67/06 takes precedence
• CPC Class Codes: C08L 75/04 Polyurethanes
• CPC Class Codes: C08L 83/04 Polysiloxanes
• CPC Class Codes: Y10S 623/924 Material characteristic

Abstract

A porous material with an appropriate surface chemistry that promotes capillary endothelialization is disclosed. The material has a porosity that is sufficient to allow capillary endothelialization and a tenaciously bound adhesion molecule that promotes the ingrowth of endothelial cells into the porosity of the material.

Claims

1. An article comprising an implantable medical device comprising a rigid, porous biomaterial selected from the group consisting of non-soluble synthetic polymers, metals and ceramics and providing a surface bearing immobilized adhesion molecules selected from the group consisting of fibronectin, laminin, collagen, and active peptide domains thereof, the adhesion molecules having been bound to each other or the surface of the biomaterial by the activation of one or more photoreactive groups covalently bound to the adhesion molecules, the photoreactive groups having been selected from the group consisting of photoreactive aryl ketones, azides, diazirines, ketenes and diazo compounds, the adhesion molecules being provided directly upon the surface in an amount suitable to promote capillary endothelialization of the device in vivo, wherein the adhesion molecule is capable of binding to the surface of a cell, and wherein the biomaterial is porous in that it provides channels or passages extending through the biomaterial and of sufficient dimensions to permit the growth of capillaries therethrough.

2. An article according to claim 1 wherein the biomaterial provides pores having an average diameter from about 5 microns to about 1 mm.

3. An article according to claim 2 wherein the biomaterial is selected from the group consisting of tetrafluoroethylene polymers, aromatic/aliphatic polyester resins, polyurethanes, and silicone rubbers.

4. An article according to claim 3 wherein the tetrafluoroethylene polymers comprise expanded polytetrafluoroethylene, the aromatic/aliphatic polyester resins comprise polyethylene terephthalate ("PET") or poly(butylene terephthalate) ("PBT"), and the silicone rubbers comprise heat cured rubbers or silicone elastomers.

5. An article according to claim 3 wherein the biomaterial is expanded polytetrafluoroethylene.

6. An article according to claim 5 wherein the expanded polytetrafluoroethylene exhibits on the order of 10 to 300 micron internodal distance.

10. An article according to claim 2 wherein the adhesion molecule comprises fibronectin and active peptide domains thereof.

11. An article according to claim 2 wherein the adhesion molecule comprises laminin and active peptide domains thereof.

12. An article according to claim 2 wherein the adhesion molecule comprises collagen and active peptide domains thereof.

13. An article according to claim 2 wherein the photoreactive groups comprise aryl ketones selected from the group consisting of acetophenone and benzophenone.

14. An article according to claim 3 wherein the article is in the form of a vascular graft.

7. A method of preparing an implantable medical device comprising the steps of:

(a) providing an implantable device comprising a rigid, porous biomaterial providing a surface, wherein the biomaterial is porous in that it provides channels or passages extending through the biomaterial and of sufficient dimensions to permit the growth of capillaries therethrough;

(b) contacting the surface with adhesion molecules selected from the group consisting of fibronectin, laminin, collagen, and active peptide domains thereof, the adhesion molecules bearing one or more latent photoreactive groups selected from the group consisting of photoreactive aryl ketones, azides, diazirines, ketenes and diazo compounds; and

(c) activating the photoreactive groups in order to immobilize the adhesion molecules by binding the adhesion molecules to each other or to the surface in an amount suitable to promote capillary endothelialization of the device in vivo.

15. A method according to claim 7 wherein the biomaterial provides pores having an average diameter from about 5 microns to about 1 mm.

16. A method according to claim 15 wherein the biomaterial is selected from the group consisting of tetrafluoroethylene polymers, aromatic/aliphatic polyester resins, polyurethanes, and silicone rubbers.

17. A method according to claim 16 wherein the tetrafluoroethylene polymers comprise expanded polytetrafluoroethylene, the aromatic/aliphatic polyester resins comprise polyethylene terephthalate ("PET") or poly(butylene terephthalate) ("PBT"), and the silicone rubbers comprise heat cured rubbers or silicone elastomers.

18. A method according to claim 17 wherein the biomaterial is expanded polytetrafluoroethylene.

19. A method according to claim 18 wherein the expanded polytetrafluoroethylene exhibits on the order of 10 to 300 micron internodal distance.

20. A method according to claim 15 wherein the adhesion molecule comprises fibronectin and active peptide domains thereof.

21. A method according to claim 15 wherein the adhesion molecule comprises laminin and active peptide domains thereof.

22. A method according to claim 15 wherein the adhesion molecule comprises collagen and active peptide domains thereof.

23. A method according to claim 15 wherein the photoreactive groups comprise aryl ketones selected from the group consisting of acetophenone and benzophenone.

24. A method according to claim 16 wherein the article is in the form of a vascular graft.

8. A method of using an implantable medical device comprising the steps of:

(a) providing an implantable device comprising a rigid, porous biomaterial providing a surface, wherein the biomaterial is porous in that it provides channels or passages extending through the biomaterial and of sufficient dimensions to permit the growth of capillaries therethrough;

(b) contacting the surface with adhesion molecules selected from the group consisting of fibronectin, laminin, collagen, and active peptide domains thereof, the adhesion molecules bearing one or more latent photoreactive groups selected from the group consisting of photoreactive aryl ketones, azides, diazirines, ketenes and diazo compounds; and

(c) activating the photoreactive groups in order to immobilize the adhesion molecules by binding the adhesion molecules to each other or to the surface; and

(d) implanting the device in contact with bodily tissues or fluids in order to promote capillary endothelialization of the device by the growth of capillary endothelial cells into the porosity of the biomaterial in vivo.

25. A method according to claim 8 wherein the biomaterial provides pores having an average diameter from about 5 microns to about 1 mm.

26. A method according to claim 25 wherein the biomaterial is selected from the group consisting of tetrafluoroethylene polymers, aromatic/aliphatic polyester resins, polyurethanes, and silicone rubbers.

27. A method according to claim 26 wherein the tetrafluoroethylene polymers comprise expanded polytetrafluoroethylene, the aromatic/aliphatic polyester resins comprise polyethylene terephthalate ("PET") or poly(butylene terephthalate) ("PBT"), and the silicone rubbers comprise heat cured rubbers or silicone elastomers.

28. A method according to claim 27 wherein the biomaterial is expanded polytetrafluoroethylene.

29. An article according to claim 28 wherein the expanded polytetrafluoroethylene exhibits on the order of 10 to 300 micron internodal distance.

30. A method according to claim 25 wherein the adhesion molecule comprises fibronectin and active peptide domains thereof.

31. A method according to claim 25 wherein the adhesion molecule comprises laminin and active peptide domains thereof.

32. A method according to claim 25 wherein the adhesion molecule comprises collagen and active peptide domains thereof.

33. A method according to claim 25 wherein the photoreactive groups comprise aryl ketones selected from the group consisting of acetophenone and benzophenone.

34. A method according to claim 26 wherein the article is in the form of a vascular graft.

9. An implantable medical device prepared by a process comprising the steps of:

(a) providing an implantable device comprising a rigid, porous biomaterial providing a surface, wherein the biomaterial is porous in that it provides channels or passages extending through the biomaterial and of sufficient dimensions to permit the growth of capillaries therethrough;

(b) contacting the surface with adhesion molecules selected from the group consisting of fibronectin, laminin, collagen, and active peptide domains thereof, the adhesion molecules bearing one or more latent photoreactive groups selected from the group consisting of photoreactive aryl ketones, azides, diazirines, ketenes and diazo compounds; and

(c) activating the photoreactive groups in order to immobilize the adhesion molecules by binding the adhesion molecules to each other or to the surface in an amount suitable to promote capillary endothelialization of the device in vivo.

35. A device according to claim 9 wherein the biomaterial provides pores having an average diameter from about 5 microns to about 1 mm.

36. A device according to claim 35 wherein the biomaterial is selected from the group consisting of tetrafluoroethylene polymers, aromatic/aliphatic polyester resins, polyurethanes, and silicone rubbers.

37. A device according to claim 36 wherein the tetrafluoroethylene polymers comprise expanded polytetrafluoroethylene, the aromatic/aliphatic polyester resins comprise polyethylene terephthalate ("PET") or poly(butylene terephthalate) ("PBT"), and the silicone rubbers comprise heat cured rubbers or silicone elastomers.

38. A device according to claim 37 wherein the biomaterial is expanded polytetrafluoroethylene.

39. A device according to claim 38 wherein the expanded polytetrafluoroethylene exhibits on the order of 10 to 300 micron internodal distance.

40. A device according to claim 35 wherein the adhesion molecule comprises fibronectin and active peptide domains thereof.

41. A device according to claim 35 wherein the adhesion molecule comprises laminin and active peptide domains thereof.

42. A device according to claim 35 wherein the adhesion molecule comprises collagen and active peptide domains thereof.

43. A device according to claim 35 wherein the photoreactive groups comprise aryl ketones selected from the group consisting of acetophenone and benzophenone.

44. A device according to claim 36 wherein the article is in the form of a vascular graft.