Method of strength enhancement of collagen constructs

• US 5,718,012 A
• Filed: 05/28/1996
• Issued: 02/17/1998
• Est. Priority Date: 05/28/1996
• Status: Expired due to Term

• Current Assignee: Organogenesis Inc. (Organogenesis Holdings, Inc.)
• Original Assignee: Organogenesis Inc. (Organogenesis Holdings, Inc.)
• Inventors: Cavallaro, John F.
• Primary Examiner(s): Prebilic, Paul B.
• Application Number:
  US08/652,666
• Time in Patent Office: 630 Days
• Field of Search: 623/11, 623/13, 128/DIG. 8, 8/94.1, 8/94.11, 8/127.5, 8/127.51, 8/127.6, 8/130.1
• US Class Current: 8/94.11
• CPC Class Codes: A61F 2/0063 Implantable repair or support meshes, e.g. hernia meshes
• CPC Class Codes: A61F 2/08 Muscles; Tendons; Ligaments sutures A61B17/04
• CPC Class Codes: A61F 2310/00365 Proteins; Polypeptides; Degradation products thereof
• CPC Class Codes: A61L 27/24 Collagen

Abstract

A method for improving the tensile strength of wet collagen threads or collagen thread constructs for implantation to replace or repair tissue or organs wherein the strength of the threads is improved by plasticizing the threads with a plasticizing agent, imparting a tensile load to the collagen thread to strain the collagen thread; allowing the load in the thread to decrease by stress-relaxation or by creep conditioning methods and finally, removing the plasticizing agent. Prosthetic devices comprising collagen threads with improved strength characteristics are intended to repair load bearing tissues such as ligaments and tendons.

Claims

1. A method for increasing the strength of at least one collagen thread, comprising:

(a) plasticizing a collagen thread with a plasticizing agent;

(b) imparting a tensile load to the collagen thread by elongation of said collagen thread to impart a strain on the thread;

(c) allowing the load in the thread to decrease substantially by stress-relaxation or by creep; and

(d) removing the plasticizing agent from the collagen thread.

2. The method of claim 1, further comprising the step:

(e) crosslinking the thread.

3. The method of claim 1, wherein the plasticizing agent is water or aqueous buffer.

4. The method of claim 1, wherein the tensile load is imparted by elongation of the thread to a strain between about 20 to 200%.

5. The method of claim 1, wherein the tensile load is applied to produce elongation of the thread to a strain between about 50 to 100%.

6. The method of claim 1, wherein the elongation is done in repeated increments.

7. The method of claim 6, wherein each increment produces a strain of about 5 to 10%.

8. The method of claim 1, wherein the load is decreased by stress-relaxation or creep to less than 0.5 grams.

9. The method of claim 2, wherein the crosslinking is accomplished by lyophilization or ultraviolet (UV) irradiation or by a crosslinking agent selected from the group consisting of acyl-azide, hexamethylene diisocyanate, bisimidates, glyoxal, polyglycerol polyglycidyl ether, adipyl chloride, ribose and other sugars, carbodiimides, and aldehydes.

10. The method of claim 9, wherein the crosslinking agent is 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC).

11. A method for increasing the strength of a multi-ply bundle of collagen threads, comprising:

(a) plasticizing a multi-ply bundle of collagen threads with water, an aqueous buffered solution, or glycerol;

(b) imparting a tensile load to said multi-ply bundle by elongating the said bundle to impart a strain on said multi-ply bundle;

(c) allowing the load in said multi-ply bundle to decrease substantially by stress-relaxation or by creep; and

,

(d) removing the plasticizing agent from said multi-ply bundle.

12. The method of claim 11, wherein the tensile load is applied to produce elongation of the thread to a strain between about 20 to 200%.

13. The method of claim 11, wherein the tensile load is applied to produce elongation of the thread to a strain between about 50 to 100%.

14. The method of claim 11, wherein said elongation is done in repeated increments.

15. The method of claim 14, wherein the each increment produces a strain of about 5% to about 10%.

16. The method of claim 11, further comprising the step of:

(e) crosslinking said multi-ply bundle.

17. The method of claim 16, further comprising the step of:

(f) sterilizing said crosslinked multi-ply bundle.

18. The method of claim 17, further comprising the step of:

(g) coating said multi-ply bundle with pharmaceuticals, growth factors, hormones, extracellular matrix components, or genetic material.

19. The method of claim 16, wherein the crosslinking is accomplished by crosslinking agent 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC).

20. The method of claim 11, wherein the multi-ply bundle is between 2 and 1000 ply.

21. The method of claim 11, wherein the multi-ply bundle is between 20 and 500 ply.

22. A method for increasing the strength of a multi-ply bundle of collagen threads, comprising:

(a) plasticizing a multi-ply bundle of collagen threads of between 2 and 1000-ply with a plasticizing agent selected from the group consisting of water, an aqueous buffered solution, or glycerol;

(b) imparting a tensile load to said multi-ply bundle by elongating the said bundle to impart a strain on said multi-ply bundle of about 5% to about 10%;

(c) allowing the load in said multi-ply bundle to decrease by stress-relaxation or by creep to less than 0.5 grams;

(d) repeating said elongation in repeated increments;

(e) removing the plasticizing agent from said multi-ply bundle;

(f) crosslinking said multi-ply bundle; and

,

(g) sterilizing said crosslinked bundle.