Vascular graft sterilization and decellularization

• US 20070260109A1
• Filed: 12/05/2006
• Published: 11/08/2007
• Est. Priority Date: 12/05/2005
• Status: Active Grant

• Current Assignee: RTI Surgical Incorporated
• Original Assignee: RTI Biologics, Inc. (Surgalign Holdings, Inc.)
• Inventors: Squillace, Donna
• Granted Patent: US 7,658,706 B2
• Time in Patent Office: Days
• US Class Current: 600/36
• CPC Class Codes: A61L 2/0088 Liquid substances
• CPC Class Codes: A61L 2/0094 Gaseous substances
• 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

The present technology is related to the field of sterilization and decellularization of allografts or xenografts, specifically to processes that achieve effective removal of the cells contained within a vascular tissue matrix and an effective reduction in potential harmful organisms to create grafts suitable for human implantation. In some embodiments, vascular grafts, vascular tissue and/or blood vessels are contacted with cleaning solution under conditions suitable conditions to reduce immune reaction in patients. More specifically, the present technology is directed to sterilization and decellularization of vascular grafts.

Claims

1. A process for making a vascular graft more suitable for implantation into a recipient, the process comprising:

(a) contacting a vascular graft with an oxidizing sterilant; and

(b) contacting the vascular graft with a cleaning solution;

wherein the contacting steps are at a temperature less than about 45°

C. and for a total contact time less than about 8 hours.

2. The process of claim 1, wherein the steps are performed in the order (a), then (b).

3. The process of claim 1, wherein at least one step is performed while the vascular implant is pressurized.

4. The process of claim 1, wherein a decellularized graft is produced.

5. The process of claim 1 wherein said implant comprises autograft, allograft or xenograft tissue, or combinations thereof.

6. The process of claim 1, wherein the oxidizing sterilant is selected from the group consisting of peroxides, oxides, hypochlorites, ozone and percarboxylic acids;

or mixtures thereof.

7. The process of claim 1, wherein the oxidizing sterilant is a percarboxylic acid selected from the group consisting of peracetic acid, perpropionic acid, perbutyric acid, peroctanoic acid, perglycolic acid, perglutaric acid, persuccinic acid, perlactic acid, percitric acid and perdecanoic acid;

or mixtures thereof.

8. The process of claim 1, wherein the oxidizing sterilant is peracetic acid.

9. The process of claim 1, wherein the cleaning solution is selected from the group consisting of solutions of cholate, alcohol ethoxylates, alkylphenol ethoxylates, alkyl polyglycosides, polyoxyethylene ethers, polyoxyethylene sorbitans, any of the Triton, Tween or Brij series of detergents, alkyl benzenesulfonates, alkyl sulfonates, alkyl phosphates, and alkyl sulfates;

or salts or mixtures thereof.

10. The process of claim 1, wherein the cleaning solution is a solution of cholate.

19. The process of claim 1, wherein during either step (a) or (b) or both, the pore volume in the vascular tissue is increased.

20. The process of claim 1, wherein during either step (a) or (b) or both, a pressure gradient across a wall of the vascular tissue is maintained.

11. A process for preparing a vascular graft from a vascular tissue, the process comprising:

(a) increasing pore volume in the vascular tissue, and

(b) contacting the vascular tissue with one or more cleaning agents.

12. The process of claim 11, comprising distending the vascular tissue while contacting the vascular tissue with a cleaning agent.

13. The process of claim 11, wherein at least one of the cleaning agents is a cell lysing agent.

14. The process of claim 11, wherein the cleaning agent contacting the vascular tissue is maintained at a temperature less than about 45°

C.

15. A process for preparing a vascular graft comprising at least one blood vessel, the process comprising:

(a) providing a pressure gradient across a wall of the blood vessel, and

(b) contacting the blood vessel with one or more cleaning agents.

16. The process of claim 15, wherein the pressure gradient is less than about 2300 mm Hg.

17. The process of claim 15, wherein the pressure gradient is in the range of from about 100 mm Hg to about 400 mm Hg.

18. The process of claim 15, wherein the pressure gradient is less than about 120 mm Hg.