Biocompatible prosthetic tissue

• US 20030130746A1
• Filed: 10/29/2002
• Published: 07/10/2003
• Est. Priority Date: 01/10/2000
• Status: Abandoned Application

• Current Assignee: St Jude Medical Incorporated (Abbott Laboratories Incorporated)
• Original Assignee: St Jude Medical Incorporated (Abbott Laboratories Incorporated)
• Inventors: Ashworth, Paul Edward, Johnson, Andrea L., Kelly, Sheila Jeanne, Ogle, Matthew Frank, McTavish, Daniel Paul
• Application Number:
  US10/283,396
• Publication Number:
  US 20030130746A1
• Time in Patent Office: Days
• US Class Current: 623/23.72
• CPC Class Codes: A61F 2/06 Blood vessels
• CPC Class Codes: A61F 2/2412 with soft flexible valve members, e.g. tissue valves shaped like natural valves check valves with flexible valve members in general F16K15/14
• CPC Class Codes: A61L 2430/40 Preparation and treatment of biological tissue for implantation, e.g. decellularisation, cross-linking
• 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
• CPC Class Codes: A61L 27/507 for artificial blood vessels apparatus for applying cells on a blood vessel prosthesis A61F2/062

Abstract

Crosslinked tissue is contacted with one or more toxicity reducing solutions to remove cytotoxicity associated with the crosslinking process. In particular, crosslinked tissue can be contacted with an inorganic sulfur-oxygen group to form chemical adducts of aldehydes and the inorganic sulfur-oxygen group. Preferably, the cytotoxicity reduced crosslinked tissue has no residual cytotoxicity. In preferred embodiments, a plurality of toxicity reducing agents are used to detoxify the tissue. Preferred toxicity reducing agents include, for example, inorganic sulfur-oxygen ions, such as bisulfate and thiosulfate, organic sulfates, amines, ammonia/ammonium, and surfactants.

Claims

1. A prosthetic tissue comprising a chemically crosslinked protein matrix having no detectable cytotoxicity without any added growth factors.

2. The prosthetic tissue of claim 1 comprising adducts of aldehyde functional groups and sulfur-oxygen compounds.

3. The prosthetic tissue of claim 1 comprising adducts of aldehyde functional groups and amines.

4. The prosthetic tissue of claim 1 comprising adducts of aldehyde functional groups and ammonia/ammonium.

5. The prosthetic tissue of claim 1 comprising adducts of aldehyde functional groups and amino acids.

6. The prosthetic tissue of claim 1 further comprising a growth factor.

7. The prosthetic tissue of claim 6 wherein the growth factor is vascular endothelial growth factor.

8. The prosthetic tissue of claim 1 further comprising compounds that attract cell precursors.

9. A heart valve prosthesis comprising the prosthetic tissue of claim 1.

10. A vascular graft comprising the prosthetic tissue of claim 1.

11. A prosthetic tissue comprising a protein matrix crosslinked with a multifunctional aldehyde having extractable residual aldehyde compound concentrations of no more than about 5×

10<sup>−

4</sup> moles of aldehyde per gram of dry tissue.

12. The prosthetic tissue of claim 11 wherein residual aldehyde concentration is no more than about 2×

10<sup>−

4</sup> moles of aldehyde per gram of dry tissue.

13. The prosthetic tissue of claim 11 having a residual multifunctional aldehyde concentration no more than about 6×

10<sup>−

5</sup> moles of multifunctional aldehyde per gram of dry tissue.

14. The prosthetic tissue of claim 11 having a residual multifunctional aldehyde concentration no more than about 1×

10<sup>−

5</sup> moles of multifunctional aldehyde per gram of dry tissue.

15. The prosthetic tissue of claim 11 having a residual formaldehyde concentration no more than about 1×

10<sup>−

4</sup> moles of formaldehyde per gram of dry tissue.

16. The prosthetic tissue of claim 11 having a residual formaldehyde concentration no more than about 2×

10<sup>−

5</sup> moles of formaldehyde per gram of dry tissue.

17. The prosthetic tissue of claim 11 having no detectable cytotoxicity without any added growth hormones.

18. A prosthetic tissue comprising adducts of aldehyde groups and inorganic sulfur-oxygen groups.

19. The prosthetic tissue of claim 18 further comprising adducts of aldehyde groups and amines.

20. The prosthetic tissue of claim 18 further comprising adducts of aldehyde groups and ammonia/ammonium.

21. The prosthetic tissue of claim 18 wherein the amino acid comprises glycine.

22. The prosthetic tissue of claim 18 further comprising a surfactant.

23. The prosthetic tissue of claim 18 wherein the inorganic sulfur-oxygen compound comprises a bisulfate compound.

24. The prosthetic tissue of claim 18 wherein the inorganic sulfur-oxygen compound comprises a thiosulfate compound.

25. The prosthetic tissue of claim 18 further comprising an adduct of organic sulfates and aldehyde groups.

26. The prosthetic tissue of claim 18 further comprising a growth factor.

27. The prosthetic tissue of claim 26 wherein the growth factor is vascular endothelial growth factor.

28. The prosthetic tissue of claim 18 further comprising compounds that attract cell precursors.

29. The prosthetic tissue of claim 18 further comprising adducts of aldehyde groups and an amino acid, adducts of aldehyde groups and ammonia/ammonium, and a surfactant.

30. A heart valve prosthesis comprising prosthetic tissue of claim 18.

31. A vascular graft comprising prosthetic tissue of claim 18.

32. A prosthetic tissue comprising adducts of aldehyde groups and ammonia/ammonium groups and adducts of aldehyde groups and sulfur-oxygen groups.

33. The prosthetic tissue of claim 32 wherein the sulfur-oxygen groups comprises organic sulfate groups.

34. A method for reducing residual reactive aldehyde groups associated with an aldehyde crosslinked tissue, the method comprising contacting an aldehyde crosslinked tissue with an inorganic sulfur-oxygen compound.

35. The method of claim 34 wherein the sulfur-oxygen compound comprises a bisulfate compound.

36. The method of claim 34 wherein the sulfur-oxygen compound comprises a thiosulfate compound.

37. The method of claim 34 further comprising contacting the tissue with an amine.

38. The method of claim 37 wherein the amine compound comprises an amino acid.

39. The method of claim 34 further comprising contacting the tissue with an ammonium ion or ammonia.

40. The method of claim 39 further comprising contacting the tissue with an amino acid.

41. The method of claim 40 further comprising contacting the tissue with a surfactant.

42. The method of claim 34 further comprising contacting the tissue with a surfactant.

43. A composition comprising an inorganic sulfur-oxygen group and an amine.