Claims for Patent: 5,762,600

Summary for Patent: 5,762,600

Title:	Blood contact surfaces employing natural subendothelial matrix and methods for making and using the same
Abstract:	This invention relates to improved vascular prostheses derived from mammalian blood vessels. The prostheses are fabricated from arterial segments from which the donor endothelium has been removed. A key aspect of this invention is the preservation of the subendothelial extracellular matrix that will serve as the blood interface of the vascular prostheses. The vessel segments are treated to reduce the likelihood of calcification and fixed with a tissue preservative. This invention results in vascular prostheses that are particularly useful for small diameter applications, such as arterial replacement requiring a diameter of 6 mm or less.
Inventor(s):	Bruchman; William Carl (Flagstaff, AZ), Switzer; Anita Jean (Parks, AZ)
Assignee:	W. L. Gore & Associates, Inc. (Newark, DE)
Application Number:	08/665,596
Patent Claims:	1. A method of producing a blood contact surface which comprises: providing a donor blood vessel, including endothelial cells attached to a subendothelial matrix layer; treating the donor blood vessel so as to remove the endothelial cells while leaving the subendothelial matrix layer in situ; treating the donor blood vessel with a proteolytic enzyme to reduce the outer diameter of the blood vessel, while protecting the subendothelial matrix layer from the proteolytic enzyme; treating the donor blood vessel to preserve the subendothelial matrix layer in situ; and employing the subendothelial matrix layer as a direct blood contact surface in an appliance. 2. The method of claim 1 which further comprises: surrounding the donor blood vessel with a sheath comprised of a material that permits the passage of macromolecules across the thickness of the sheath to and from the blood vessel while resisting ingrowth of cells from tissues surrounding the blood vessel when implanted. 3. The method of claim 1 which further comprises: eating the donor blood vessel to prevent calcification with a solution of chloroform and methanol. 4. The method of claim 1 wherein the proteolytic enzyme is selected from at least one member of a group consisting of collagenase, papain, trypsin, chymotrypsin, and elastase. 5. A method of producing a blood contact surface which comprises: providing a donor blood vessel, including endothelial cells attached to a subendothelial matrix layer, having an exterior surface and an interior surface; treating the donor blood vessel so as to remove the endothelial cells while leaving the subendothelial matrix layer in situ; treating the donor blood vessel to preserve the subendothelial matrix layer in situ; surrounding the exterior surface of the donor blood vessel with a sheath comprised of a material that permits the passage of macromolecules across the thickness of the sheath to and from the blood vessel while resisting ingrowth of cells from tissues surrounding the blood vessel when implanted; and employing the subendothelial matrix layer as a direct blood contact surface in an appliance comprising an artificial blood vessel. 6. The method of claim 5 which further comprises: treating the donor blood vessel to prevent calcification with a solution of chloroform and methanol. 7. A process of producing a direct blood contact surface on an artificial blood vessel which comprises: providing a natural blood contact surface derived from a donor blood vessel, including an endothelial cell layer attached to a subendothelial matrix layer; stripping the endothelial cell layer from the subendothelial matrix layer so as to leave the subendothelial matrix layer in situ; treating the blood contact surface to preserve the subendothelial matrix layer in situ; surrounding the donor blood vessel with a sheath comprising a porous polytetrafluoroethylene material that is permeable to macromolecules but resistant to cell ingrowth; and employing the preserved subendothelial matrix layer substantially free of endothelial cells as a direct blood contact surface. 8. The process of claim 7 which further comprises: treating the donor blood vessel to prevent calcification with a solution of chloroform and methanol. 9. A process of producing a direct blood contact surface which comprises: providing a natural blood contact surface derived from a donor blood vessel, including an endothelial cell layer attached to a subendothelial matrix layer; stripping the endothelial cell layer from the subendothelial matrix layer so as to leave the subendothelial matrix layer in situ; treating the donor blood vessel to reduce the outer diameter of the blood vessel with a proteolytic enzyme, while protecting the subendothelial matrix layer from the proteolytic enzyme; treating the blood contact surface to preserve the subendothelial matrix layer in situ; and employing the preserved subendothelial matrix layer substantially free of endothelial cells as a direct blood contact surface. 10. The process of claim 9 which further comprises: surrounding the donor blood vessel with a sheath comprised of a material that permits the passage of macromolecules across the thickness of the sheath to and from the blood vessel while resisting ingrowth of cells from tissues surrounding the blood vessel when implanted. 11. The process of claim 9 which further comprises: treating the donor blood vessel to prevent calcification with a solution of chloroform and methanol. 12. The process of claim 9 wherein the proteolytic enzyme is selected from at least one member of a group consisting of collagenase, papain, trypsin, chymotrypsin, and elastase. 13. A method of producing a direct blood contact surface with improved patency performance which comprises: providing a natural blood contact surface derived from a donor, including an endothelial cell layer attached to a subendothelial matrix layer; stripping the endothelial cell layer from the subendothelial matrix layer so as to leave the subendothelial matrix layer in situ; treating the subendothelial matrix layer with a solution of ammonium hydroxide to improve patency; treating the subendothelial matrix layer to preserve the subendothelial matrix layer; and employing the preserved subendothelial matrix layer substantially free of endothelial cells as a direct blood contact surface. 14. The method of claim 13 which further comprises: surrounding the blood contact surface with a sheath comprised of a material that permits the passage of macromolecules across the thickness of the sheath to and from the blood contact surface while resisting ingrowth of cells from tissues surrounding the blood contact surface when implanted. 15. The method of claim 13 which further comprises: treating the blood contact surface to prevent calcification with a solution of chloroform and methanol. 16. The method of claim 13 which further comprises: treating the blood contact surface with a proteolytic enzyme to reduce the outer diameter of the blood contact surface of the blood contact surface, while protecting the subendothelial matrix layer from the proteolytic enzyme. 17. The method of claim 16 wherein the proteolytic enzyme is selected from at least one member of a group consisting of collagenase, papain, trypsin, chymotrypsin, and elastase. 18. The method of claim 1 wherein the subendothelial matrix layer comprises chondroitin sulfate proteoglycans. 19. The method of claim 18 wherein the subendothelial matrix layer further comprises glycosaminoglycan-bearing proteoglycans. 20. The method of claim 18 wherein the subendothelial matrix layer further comprises fibronectin. 21. The method of claim 19 wherein the subendothelial matrix layer further comprises fibronectin. 22. The method of claim 5 wherein the subendothelial matrix layer comprises chondroitin sulfate proteoglycans. 23. The method of claim 22 wherein the subendothelial matrix layer further comprises glycosaminoglycan-bearing proteoglycans. 24. The method of claim 22 wherein the subendothelial matrix layer further comprises fibronectin. 25. The method of claim 23 wherein the subendothelial matrix layer further comprises fibronectin. 26. The method of claim 7 wherein the subendothelial matrix layer comprises chondroitin sulfate proteoglycans. 27. The method of claim 26 wherein the subendothelial matrix layer further comprises glycosaminoglycan-bearing proteoglycans. 28. The method of claim 26 wherein the subendothelial matrix layer further comprises fibronectin. 29. The method of claim 27 wherein the subendothelial matrix layer further comprises fibronectin. 30. The method of claim 9 wherein the subendothelial matrix layer comprises chondroitin sulfate proteoglycans. 31. The method of claim 30 wherein the subendothelial matrix layer further comprises glycosaminoglycan-bearing proteoglycans. 32. The method of claim 30 wherein the subendothelial matrix layer further comprises fibronectin. 33. The method of claim 31 wherein the subendothelial matrix layer further comprises fibronectin. 34. The method of claim 13 wherein the subendothelial matrix layer comprises chondroitin sulfate proteoglycans. 35. The method of claim 34 wherein the subendothelial matrix layer further comprises glycosaminoglycan-bearing proteoglycans. 36. The method of claim 34 wherein the subendothelial matrix layer further comprises fibronectin. 37. The method of claim 35 wherein the subendothelial matrix layer further comprises fibronectin. 38. A method of producing a blood contact surface which comprises: providing a donor blood vessel, including endothelial cells attached to a subendothelial matrix layer; treating the donor blood vessel so as to remove only the endothelial cells while leaving the subendothelial matrix layer in situ; treating the donor blood vessel to preserve the subendothelial matrix layer; treating the donor blood vessel with a proteolytic enzyme to reduce the outer diameter of the blood vessel, while protecting the subendothelial matrix layer from the proteolytic enzyme; and employing the subendothelial matrix layer as a direct blood contact surface in an appliance. 39. The method of claim 38 wherein the subendothelial matrix layer comprises chondroitin sulfate proteoglycans. 40. The method of claim 39 wherein the subendothelial matrix layer further comprises glycosaminoglycan-bearing proteoglycans. 41. The method of claim 39 wherein the subendothelial matrix layer further comprises fibronectin. 42. The method of claim 40 wherein the subendothelial matrix layer further comprises fibronectin. 43. A method of producing a blood contact surface which comprises: providing a donor blood vessel, including endothelial cells attached to a subendothelial matrix layer; treating the donor blood vessel so as to remove only the endothelial cells while leaving the subendothelial matrix layer in situ; treating the donor blood vessel to preserve the subendothelial matrix layer; employing the subendothelial matrix layer as a direct blood contact surface in an appliance, wherein the appliance comprises an artificial blood vessel having an exterior surface and an interior surface; and surrounding the exterior surface of the donor blood vessel with a sheath, wherein the sheath comprises a material which permits the passage of macromolecules across the thickness of the sheath to and from the donor blood vessel while resisting ingrowth of cells from tissue surrounding the donor blood vessel when implanted. 44. The method of claim 43 wherein the subendothelial matrix layer comprises chondroitin sulfate proteoglycans. 45. The method of claim 44 wherein the subendothelial matrix layer further comprises glycosaminoglycan-bearing proteoglycans. 46. The method of claim 44 wherein the subendothelial matrix layer further comprises fibronectin. 47. The method of claim 45 wherein the subendothelial matrix layer further comprises fibronectin. 48. A process of producing a direct blood contact surface which comprises: providing a natural blood contact surface derived from a donor blood vessel, including an endothelial cell layer attached to a subendothelial matrix layer; stripping only the endothelial cell layer from the subendothelial matrix layer so as to leave the subendothelial matrix layer in situ; treating the blood contact surface to preserve the subendothelial matrix layer; surrounding the donor blood vessel with a sheath comprised of a porous polytetrafluoroethylene material that is permeable to macromolecules, but resistant to cell ingrowth; and employing the preserved subendothelial matrix layer substantially free of endothelial cells as a direct blood contact surface. 49. The method of claim 48 wherein the subendothelial matrix layer comprises chondroitin sulfate proteoglycans. 50. The method of claim 49 wherein the subendothelial matrix layer further comprises glycosaminoglycan-bearing proteoglycans. 51. The method of claim 49 wherein the subendothelial matrix layer further comprises fibronectin. 52. The method of claim 50 wherein the subendothelial matrix layer further comprises fibronectin. 53. A process of producing a direct blood contact surface which comprises: providing a natural blood contact surface derived from a donor blood vessel, including an endothelial cell layer attached to a subendothelial matrix layer; stripping only the endothelial cell layer from the subendothelial matrix layer so as to leave the subendothelial matrix layer in situ; treating the blood contact surface to preserve the subendothelial matrix layer; treating the donor blood vessel with a proteolytic enzyme to reduce the outer diameter of the blood vessel, while protecting the subendothelial matrix layer from the proteolytic enzyme; and employing the preserved subendothelial matrix layer substantially free of endothelial cells as a direct blood contact surface. 54. The method of claim 53 wherein the subendothelial matrix layer comprises chondroitin sulfate proteoglycans. 55. The method of claim 54 wherein the subendothelial matrix layer further comprises glycosaminoglycan-bearing proteoglycans. 56. The method of claim 54 wherein the subendothelial matrix layer further comprises fibronectin. 57. The method of claim 55 wherein the subendothelial matrix layer further comprises fibronectin. 58. A process of producing a direct blood contact surface which comprises: providing a natural blood contact surface derived from a donor blood vessel, including an endothelial cell layer attached to a subendothelial matrix layer; stripping only the endothelial cell layer from the subendothelial matrix layer so as to leave the subendothelial matrix layer in situ; treating the blood contact surface to preserve the subendothelial matrix layer; treating the donor blood vessel with a proteolytic enzyme to reduce the outer diameter of the blood vessel, while protecting the subendothelial matrix layer from the proteolytic enzyme, wherein the proteolytic enzyme selected from at least one member of a group consisting of collagenase, papain, trypsin, chymotrypsin, and elastase; and employing the preserved subendothelial matrix layer substantially free of endothelial cells as a direct blood contact surface. 59. The method of claim 58 wherein the subendothelial matrix layer comprises chondroitin sulfate proteoglycans. 60. The method of claim 59 wherein the subendothelial matrix layer further comprises glycosaminoglycan-bearing proteoglycans. 61. The method of claim 59 wherein the subendothelial matrix layer further comprises fibronectin. 62. The method of claim 60 wherein the subendothelial matrix layer further comprises fibronectin.

Details for Patent 5,762,600

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Smith & Nephew, Inc.	SANTYL	collagenase	Ointment	101995	06/04/1965		2014-04-29