Biocompatible prosthetic tissue

• US 6,471,723 B1
• Filed: 01/10/2000
• Issued: 10/29/2002
• Est. Priority Date: 01/10/2000
• Status: Expired due to Term

• 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, McTavish, Daniel Paul, Ogle, Matthew Frank
• Primary Examiner(s): O'Connor, Cary E.
• Application Number:
  US09/480,437
• Time in Patent Office: 1,023 Days
• Field of Search: 623/2.42, 623/926, 623/27.72, 435/40.5, 8 9/411, 8 9/433
• US Class Current: 623/2.42
• 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 comprising aldehyde adducts, the protein matrix having immunological rejection sufficiently suppressed to permit xenograft transplantation and the protein matrix having no detectable cytotoxicity as evaluated in a culture medium 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 and soaked in formaldehyde 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 19 wherein the amine comprises glycine.

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

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.