Methods for treating implantable biological tissues to mitigate the calcification thereof and bioprosthetic articles treated by such methods

• US 20040030405A1
• Filed: 02/05/2003
• Published: 02/12/2004
• Est. Priority Date: 07/29/1994
• Status: Active Grant

• Current Assignee: Alain F. Carpentier, Sophie Carpentier
• Original Assignee: Alain F. Carpentier, Sophie Carpentier
• Inventors: Carpentier, Alain F., Carpentier, Sophie
• Granted Patent: US 7,029,434 B2
• Time in Patent Office: Days
• US Class Current: 623/23.72
• CPC Class Codes: A61L 2400/02 Treatment of implants to prevent calcification or mineralisation in vivo
• CPC Class Codes: A61L 27/3604 characterised by the human or animal origin of the biological material, e.g. hair, fascia, fish scales, silk, shellac, pericardium, pleura, renal tissue, amniotic membrane, parenchymal tissue, fetal tissue, muscle tissue, fat tissue, enamel
• 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: Y10S 623/915 Method or apparatus for preparing biological material

Abstract

A method for treating fixed biological tissue inhibits calcification of the biological tissue following implantation thereof in a mammalian body. The method includes placing the biological tissue in contact with glutaraldehyde and then heating the glutaraldehyde. Alternatively, methods other than heating (e.g., chemical or mechanical means), for effecting polymerization of the glutaraldehyde may also be utilized. Alternatively, the tissue may be heat treated prior to fixing thereof. Alternatively, methods other than glutaraldehyde may also be used for fixing the tissue. The biological tissue may be so treated at any time prior to implantation thereof in a mammalian body.

Claims

1. A method for treating glutaraldehyde fixed biological tissue to inhibit calcification of said tissue following implantation in a mammalian body, said method comprising the steps of:

a) placing the biological tissue in contact with glutaraldehyde; and

b) heating the glutaraldehyde.

2. The method as recited in claim 1 wherein the step, of placing the biological tissue in contact with glutaraldehyde comprises placing the biological tissue in contact with an approximately 0.625% solution of glutaraldehyde comprising:

a) approximately 26 ml/l glutaraldehyde (25%);

b) approximately 4.863 g/l HEPES buffer;

c) approximately 2.65 g/l MgCl₂.6H₂0;

d) approximately 4.71 g/l NaCl;

e) balance of solution double filtered H₂O; and

f) sufficient NaOH to adjust pH to approximately 7.4.

3. The method as recited in claim 1 wherein the step of heating the glutaraldehyde comprises heating said solution of glutaraldehyde to approximately 35-55°

C.

4. The method as recited in claim 1 wherein the step of heating the glutaraldehyde comprises heating said glutaraldehyde for approximately 4-22 weeks.

5. The method as recited in claim 1 wherein the step of heating the glutaraldehyde comprises heating said glutaraldehyde during the process of fixing the biological tissue.

6. The method as recited in claim 1 wherein the step of heating the glutaraldehyde comprises heating said glutaraldehyde after fixing of the biological tissue and before storage of the biological tissue.

7. The method as recited in claim 1 wherein the step of heating the glutaraldehyde comprises heating said glutaraldehyde after storage of the biological tissue.

8. The method as recited in claim 6 wherein the step of heating the glutaraldehyde comprises heating said glutaraldehyde in which the biological tissue is subsequently stored.

9. The method as recited in claim 1 wherein the biological tissue is stored in a glutaraldehyde solution after fixation of the tissue has been completed and wherein the step of heating the solution of glutaraldehyde comprises heating the solution of glutaraldehyde in which the biological tissue is stored.

10. The method as recited in claim 1 wherein the tissue is treated, after fixation treatment with an antimineralization treatment solution containing glutaraldehyde, and wherein the step of heating the glutaraldehyde comprises heating glutaraldehyde containing antimineralization treatment solution with which said tissue is treated.

16. A bioprosthesis formed by the process of claim 1.

17. The bioprosthesis of claim 16 wherein the fixed biological tissue comprises:

a) a cardiac valve;

b) vascular tissue;

c) skin;

d) dura mater;

e) pericardium;

f) a ligament; and

/or

g) a tendon.

18. The bioprosthesis of claim 16 wherein the step of heating the glutaraldehyde comprises heating said glutaraldehyde during fixing of the biological tissue.

19. The bioprosthesis of claim 16 wherein the step of heating the glutaraldehyde comprises heating said glutaraldehyde after fixing of the biological tissue and before storage of the biological tissue.

20. The bioprosthesis of claim 16 wherein the step of heating the glutaraldehyde comprises heating said glutaraldehyde after storage of the biological tissue.

21. The bioprosthesis of claim 16 wherein the step of heating the glutaraldehyde comprises heating glutaraldehyde containing antimineralization solution with which said tissue is treated.

11. A method for treating glutaraldehyde fixed biological tissue to inhibit calcification following implantation in a mammalian body, the method comprising the steps of:

a) disposing the biological tissue in a solution of glutaraldehyde; and

b) causing the glutaraldehyde to polymerize.

12. The method of claim 11 wherein step (b) comprises applying heat to cause said glutaraldehyde to polymerize.

13. The method of claim 11 wherein step (b) comprises adding a chemical to the glutaraldehyde to cause the glutaraldehyde to polymerize.

14. The method of claim 11 wherein step (b) comprises utilizing mechanical means to cause the glutaraldehyde to polymerize.

15. The method as recited in claim 11 wherein the step of disposing the biological tissue in a solution of glutaraldehyde comprises dispensing the biological tissue in an approximately 0.625% solution of glutaraldehyde comprising:

a) approximately 26 ml/l glutaraldehyde (25%);

b) approximately 4.863 g/l HEPES buffer;

c) approximately 2.65 g/l MgCl₂.6H₂0;

d) approximately 4.71 g/l NaCl;

e) balance of solution double filtered H₂0; and

f) sufficient NaOH to adjust pH to approximately 7.4.

22. A bioprosthesis formed by the process of claim 11.

23. The bioprosthesis of claim 22 wherein the fixed biological tissue comprises:

a) a cardiac valve;

b) vascular tissue;

c) skin;

d) dura mater;

e) pericardium;

f) a ligament; and

/or

g) a tendon.

24. The bioprosthesis of claim 22 wherein the step of causing the glutaraldehyde to polymerize comprises heating said glutaraldehyde.

25. The bioprosthesis of claim 22 wherein the step of causing the glutaraldehyde to polymerize is carried out during fixing of the biological tissue and before storage of the bioprosthesis.

26. The bioprosthesis of claim 22 wherein the step of causing the glutaraldehyde to polymerize is carried out after fixation but prior to bioprosthesis.

27. The bioprosthesis of claim 22 wherein the step of causing the glutaraldehyde to polymerize is carried out concomitantly with exposure of the bioprosthesis to a glutaraldehyde containing antimineralization treatment solution.

28. The bioprosthesis of claim 22 wherein the step of causing the glutaraldehyde to polymerize is carried out after fixation and during storage of the bioprosthesis in a glutaraldehyde—

containing storage solution.