Method and kit for rapid preparation of autologous tissue medical devices

• US 6,214,055 B1
• Filed: 10/30/1998
• Issued: 04/10/2001
• Est. Priority Date: 10/30/1998
• Status: Expired due to Fees

• Current Assignee: Mures Cardiovascular Research, Inc.
• Original Assignee: Mures Cardiovascular Research, Inc.
• Inventors: Simionescu, Dan, Simionescu, Agneta
• Primary Examiner(s): Milano, Michael J.
• Application Number:
  US09/183,426
• Time in Patent Office: 893 Days
• Field of Search: 623/915-918, 623/1.47, 623/1.48, 623/2-3-, 623/2.42, 623/920-922, 623/23.72
• US Class Current: 623/23.72
• CPC Class Codes: A61F 2/2415 Manufacturing methods
• 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 27/3645 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 for the rapid chemical treatment of autologous connective tissues which enhances biocompatibility by reducing cytotoxicity, immunogenicity and calcification without impairing the mechanical properties of the fixed tissue. The procedure includes a short exposure of the autologous biological tissue to a dialdehyde fixative followed by the rapid neutralization of excess aldehyde with an aminoacid solution.

Claims

1. A method for rapid fixation and neutralization of autologous biological tissue that renders the tissue suitable for animal and human implantation comprising:

treating a animal or human tissue with an effective amount of glutaraldehyde which promotes tissue crosslinking; and

treating the animal or human tissue with an unbranched alpha amino acid solution.

2. The method of claim 1 wherein the rapid fixation and neutralization of autologous biological tissues is performed onto connective tissues selected from the group consisting of pericardium, cardiac valves, arterial and venous walls, fascia lata, tendons, skin, trachea and medical devices that incorporate rapidly fixed and neutralized tissue.

3. The method of claim 1 wherein the unbranched alpha amino acid is of such a concentration as to neutralize residual glutaraldehyde.

4. The method of claim 1 wherein the unbranched alpha amino acid solution has a pH of about 7.4.

5. The method of claim 1 wherein the treating of the animal or human tissue with the unbranched alpha amino acid solution is for a period of about 8 to about 15 minutes.

6. A method for the rapid chemical treatment of autologous connective tissues which enhances biocompatibility by reducing cytotoxicity, immunogenicity and calcification without impairing the mechanical properties of the tissue comprising:

exposing the autologous connective tissue to a dialdehyde fixative for about 8 to about 15 minutes; and

rapidly neutralizing excess aldehyde on the tissue with an unbranched alpha aminoacid solution.

7. The method of claim 6 wherein the dialdehyde fixative contains an effective amount of dialdehyde to promote tissue crosslinking.

8. The method of claim 6 wherein the aminoacid solution is of such a concentration as to neutralize residual dialdehyde fixative.

9. A method for rapid fixation and neutralization of autologous biological tissue that renders the tissue suitable for animal and human implantation comprising:

treating a animal or human tissue with an effective amount of glutaraldehyde which promotes tissue crosslinking for a period of about 8 to about 15 minutes; and

treating the animal or human tissue with an unbranched alpha aminoacid solution having a pH of about 7.4 for a period of about 8 to about 30 minutes.

10. The method of claim 9 wherein the effective amount of glutaraldehyde is about 0.2 to 0.7% in a buffered solution.

11. The method of claim 9 wherein the rapid fixation and neutralization of autologous biological tissues is performed onto connective tissues selected from the group consisting of pericardium, cardiac valves, arterial and venous walls, fascia lata, tendons, skin, trachea and medical devices that incorporate rapidly fixed and neutralized tissue.

12. A method for the rapid chemical treatment of autologous connective tissues which enhances biocompatibility by reducing cytotoxicity, immunogenicity and calcification without impairing the mechanical properties of the autologous connective tissue comprising:

exposing the autologous connective tissue to a dialdehyde fixative; and

neutralizing excess aldehyde on the autologous connective tissue with an unbranched alpha aminoacid solution for about 8 to about 30 minutes.

13. The method of claim 12 wherein the neutralizing of excess aldehyde on the autologos connective tissue is for a first period of about 8 to about 15 minutes and a second period of about 8 to about 15 minutes.

14. The method of claim 12 wherein the aminoacid solution has a pH of about 7.4.

15. The method of claim 12 wherein the exposing of the autologous connective tissue to the dialdehyde fixative is for a period of about 8 to about 15 minutes.

16. The method of claim 12 wherein the dialdehyde fixative contains an effective amount of dialdehyde to promote tissue crosslinking.