Process for reducing mineralization of tissue used in transplantation

• US 20030118981A1
• Filed: 12/02/2002
• Published: 06/26/2003
• Est. Priority Date: 03/30/2001
• Status: Active Grant

• Current Assignee: Mark W. Torrianni
• Original Assignee: Mark W. Torrianni
• Inventors: Torrianni, Mark W.
• Granted Patent: US 7,078,163 B2
• Time in Patent Office: Days
• US Class Current: 435/1.1
• CPC Class Codes: A61L 27/3625 Vascular tissue, e.g. heart valves
• CPC Class Codes: A61L 27/3645 Connective tissue
• CPC Class Codes: A61L 27/3687 characterised by the use of chemical agents in the treatment, e.g. specific enzymes, detergents, capping agents, crosslinkers, anticalcification agents

Abstract

A method of making a tissue-derived implantable medical device that includes contacting the tissue with a composition comprising at least one oxidizing agent prior to implantation of the medical device.

Claims

1. A method of making a tissue-derived implantable medical device, the method comprising contacting the tissue with a composition comprising at least one oxidizing agent prior to implantation of the medical device.

2. The method of claim 1 further comprising rinsing the tissue to remove at least a portion of the oxidizing agent.

3. The method of claim 1 wherein the tissue is obtained from a mammal.

4. The method of claim 1 wherein the tissue-derived implantable medical device is rendered resistant to in vivo pathologic calcification.

5. The method of claim 1 wherein the tissue-derived implantable medical device comprises a heart valve.

6. The method of claim 5 wherein the heart valve is derived from porcine aortic root tissue, bovine aortic root tissue, porcine pericardium, bovine pericardium, bovine veins, porcine veins, bovine arteries, or porcine arteries.

7. The method of claim 1 wherein the oxidizing agent is selected from the group of sodium hypochlorite, sodium bromate, sodium hydroxide, sodium iodate, performic acid, sodium periodate, periodic acid, potassium dichromate, potassium permanganate, chloramine T, peracetic acid, and combinations thereof.

8. The method of claim 7 wherein the oxidizing agent is selected from the group of sodium hypochlorite, performic acid, periodic acid, peracetic acid, and combinations thereof.

9. The method of claim 8 wherein the sodium hypochlorite is in a concentration of about 2 mM to about 20 mM.

10. The method of claim 1 wherein the composition comprising an oxidizing agent further comprises at least one chelating agent.

11. The method of claim 10 wherein the chelating agent is selected from the group of ethylenediaminetetraacetic acid, ethylenebis(oxyethylenenitrilo)tetraacetic acid (EGTA), citric acid, salts thereof, and combinations thereof.

12. The method of claim 1 wherein the composition comprising at least one oxidizing agent further comprises at least one buffering agent.

13. The method of claim 12 wherein the buffering agent has a pKa of about 7.0 to about 7.5.

14. The method of claim 12 wherein the buffering agent is an organic buffer.

15. The method of claim 14 wherein the buffering agent is selected from the group of HEPES, TES, BES, MOPS, PIPES, MES, and combinations thereof.

16. The method of claim 1 wherein contacting the tissue with a composition comprising at least one oxidizing agent is carried out for at least about 24 hours.

17. The method of claim 1 further contacting the tissue with a detergent composition.

18. The method of claim 17 wherein the detergent composition comprises at least one reducing agent.

19. The method of claim 17 wherein the detergent composition comprises an ionic detergent or a nonionic detergent.

20. The method of claim 17 wherein contacting the tissue with the detergent composition is carried out at a temperature of at least about 30°

C.

21. The method of claim 17 wherein contacting the tissue with the detergent composition comprises sonicating the tissue while immersed in the composition.

22. The method of claim 17 wherein contacting the tissue with a detergent composition comprises contacting it with a first and a second detergent composition.

23. The method of claim 22 wherein the first detergent composition comprises an ionic detergent and the second detergent composition comprises a nonionic detergent.

24. The method of claim 23 wherein the first and/or the second detergent compositions comprise at least one reducing agent.

25. The method of claim 17 wherein contacting the tissue with a detergent composition is carried out after contacting the tissue with the composition comprising the oxidizing agent.

26. The method of claim 1 further comprising treating the tissue with a fixative composition.

27. The method of claim 26 wherein treating the tissue with a fixative composition comprises using a glutaraldehyde- or a carbodiimide-based process.

28. The method of claim 27 wherein the fixative composition further comprises at least one buffering agent.

29. A method for reducing mineralization of a tissue-derived implantable medical device, the method comprising:

contacting the tissue with a composition comprising at least one oxidizing agent;

rinsing the tissue to remove at least a portion of the oxidizing agent; and

contacting the tissue with a detergent composition comprising at least one reducing agent prior to implantation of the medical device.

30. A method for reducing mineralization of a tissue-derived implantable medical device, the method comprising:

contacting the tissue with a non-phosphate buffered organic saline solution;

contacting the tissue with a composition comprising at least one oxidizing agent;

rinsing the tissue to remove at least a portion of the oxidizing agent;

contacting the tissue with a first detergent composition comprising at least one ionic detergent and at least one reducing agent;

rinsing the tissue to remove at least a portion of the first detergent composition; and

contacting the tissue with a second detergent composition comprising at least one nonionic detergent, and at least one reducing agent prior to implantation of the medical device.