TREATING BIOLOGICAL TISSUES TO MITIGATE POST-IMPLANTATION CALCIFICATION

• US 20070255423A1
• Filed: 05/04/2007
• Published: 11/01/2007
• Est. Priority Date: 09/21/1998
• Status: Active Grant

• Current Assignee: Edwards Lifesciences Corporation
• Original Assignee: Edwards Lifesciences Corporation
• Inventors: Carpentier, Alain, Cunanan, Crystal, Sarner, H. Chris, Loshbaugh, Christine, Helmus, Michael, Carpentier, Sophie, Quintero, Lillian
• Granted Patent: US 8,236,241 B2
• Time in Patent Office: Days
• US Class Current: 623/23.720
• CPC Class Codes: A61L 2/0088 Liquid substances
• CPC Class Codes: A61L 2400/02 Treatment of implants to prevent calcification or mineralisation in vivo
• CPC Class Codes: A61L 2430/40 Preparation and treatment of biological tissue for implantation, e.g. decellularisation, cross-linking
• 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 27/3641 characterised by the site of application in the body materials for artificial blood vessels A61L27/507; materials for use in artificial skin A61L27/60
• CPC Class Codes: A61L 27/3645 Connective tissue
• CPC Class Codes: A61L 27/3683 subjected to a specific treatment prior to implantation, e.g. decellularising, demineralising, grinding, cellular disruption/non-collagenous protein removal, anti-calcification, crosslinking, supercritical fluid extraction, enzyme treatment
• 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 27/3691 characterised by physical conditions of the treatment, e.g. applying a compressive force to the composition, pressure cycles, ultrasonic/sonication or microwave treatment, lyophilisation
• CPC Class Codes: A61L 33/12 Polypeptides, proteins or derivatives thereof , e.g. degradation products thereof
• CPC Class Codes: A61P 19/00 Drugs for skeletal disorders
• CPC Class Codes: Y10S 623/901 Method of manufacturing prosthetic device
• CPC Class Codes: Y10S 623/915 Method or apparatus for preparing biological material
• CPC Class Codes: Y10S 623/917 Collagen
• CPC Class Codes: Y10S 623/92 Method or apparatus for preparing or treating prosthetic

Abstract

A method for fixation of biological tissues, and bioprosthetic devices prepared by such method. The method generally comprises the steps of A) fixing the tissue, B) treating the tissue with a mixture of i) a denaturant, ii) a surfactant and iii) a crosslinking agent, C) fabricating or forming the bioprosthesis (e.g., forming the tissue and attaching any non-biological components thereto) and D) subjecting the bioprosthesis to terminal sterilization.

Claims

1. A method for treating biological tissue which contains connective tissue protein to reduce the potential for post-implantation calcification and thrombogenicity, said method comprising the steps of:

a. crosslinking the connective tissue protein within the biological tissue with a crosslinking agent;

b. after crosslinking, immersing the biological tissue in a first solution containing a crosslinking agent and heating the first solution to a temperature of about 50°

C. for a first period of time;

then

c. assembling the bioprosthesis by attaching any non-biological components of the prosthesis to the biological tissue; and

,

d. subjecting the bioprosthesis to a sterilant by immersing the bioprosthesis in a sterilizing solution containing glutaraldehyde and heating the second solution to a temperature of 37.5±

2.5°

C. for a sterilizing period of time.

2. The method of claim 1, wherein the first period of time is between 2 to 24 hours.

3. The method of claim 1, wherein the first solution contains a mixture of the crosslinking agent, a denaturing agent and a surfactant.

4. The method of claim 1, wherein the crosslinking agent of the first solution is glutaraldehyde.

5. The method of claim 1, wherein the sterilizing period of time is between 1-6 days.

6. The method of claim 1, further including, between the steps of crosslinking and immersing the biological tissue in the first solution, immersing the biological tissue in a second solution containing a mixture of a crosslinking agent, a denaturing agent and a surfactant.

7. The method of claim 1, wherein the biological tissue is pericardium and the bioprosthesis is a heart valve.

8. The method of claim 1, wherein the step of subjecting the bioprosthesis to a sterilant is carried out in a sealed container and the method further comprises storing the bioprosthesis within the sealed container.

9. A method for treating biological tissue which contains connective tissue protein to reduce the potential for post-implantation calcification and thrombogenicity, said method comprising the steps of:

crosslinking the connective tissue protein within the biological tissue with glutaraldehyde;

then,

immersing the biological tissue in a first solution containing glutaraldehyde and heating the first solution to a temperature of about 50°

C. for a first period of time;

then,

immersing the biological tissue in a second solution containing a mixture of a crosslinking agent, a denaturing agent and a surfactant; and

then,

immersing the biological tissue in a sterilizing solution containing glutaraldehyde and heating the sterilizing solution to a temperature of 37.5±

2.5°

C. for a sterilizing period of time.

10. The method of claim 9, wherein the first period of time is between 2 to 24 hours.

11. The method of claim 9, wherein the first solution contains a mixture of the glutaraldehyde, a denaturing agent and a surfactant.

12. The method of claim 9, wherein the second solution contains a mixture of formaldehyde, ethanol and Tween-80.

13. The method of claim 9, wherein the sterilizing period of time is between 1-6 days.

14. The method of claim 9, wherein the biological tissue is pericardium and the method further includes forming a heart valve from the treated pericardium.

15. A method for fabricating a bioprosthetic heart valve to reduce the potential for post-implantation calcification and thrombogenicity, said method comprising the steps of:

crosslinking pericardial tissue with glutaraldehyde;

immersing the pericardial tissue in a first solution containing glutaraldehyde and heating the first solution to a temperature of about 50°

C. for a first period of time;

immersing the pericardial tissue in a second solution containing a mixture of a crosslinking agent, a denaturing agent and a surfactant;

assembling a bioprosthetic heart valve by attaching any non-biological components of the heart valve to the pericardial tissue; and

,

immersing the bioprosthetic heart valve in a sterilizing solution containing glutaraldehyde and heating the sterilizing solution to a temperature of 37.5±

2.5°

C. for a sterilizing period of time.

16. The method of claim 15, wherein the first period of time is between 2 to 24 hours.

17. The method of claim 15, wherein the first solution contains a mixture of the glutaraldehyde, a denaturing agent and a surfactant.

18. The method of claim 15, wherein the second solution contains a mixture of formaldehyde, ethanol and Tween-80.

19. The method of claim 15, wherein the sterilizing period of time is between 1-6 days.

20. The method of claim 15, wherein the step of immersing the bioprosthetic heart valve in a sterilizing solution is carried out in a sealed container and the method further comprises storing the bioprosthetic heart valve within the sealed container.