Method of manufacturing pliable biological grafts materials

• US 5,376,110 A
• Filed: 06/09/1993
• Issued: 12/27/1994
• Est. Priority Date: 02/14/1991
• Status: Expired due to Term

• Current Assignee: Edwards Lifesciences Corporation
• Original Assignee: Baxter International Inc.
• Inventors: Wang, Edwin, Kuo, Chris, Hata, Cary, Tu, Roger
• Primary Examiner(s): Isabella, David
• Assistant Examiner(s): BRITTINGHAM, DEBRA
• Application Number:
  US08/074,018
• Time in Patent Office: 566 Days
• Field of Search: 623/1, 623/11, 623/12, 623/13, 128/DIG. 8, 600/36
• US Class Current: 600/36
• CPC Class Codes: A61F 2/06 Blood vessels
• CPC Class Codes: A61F 2/062 Apparatus for the production of blood vessels made from natural tissue or with layers of living cells prostheses made from natural tissue or living cells A61L27/507
• CPC Class Codes: A61F 2310/00365 Proteins; Polypeptides; Degradation products thereof
• CPC Class Codes: A61L 27/24 Collagen
• CPC Class Codes: Y10S 128/08 Collagen
• CPC Class Codes: Y10S 623/921 Blood vessel

Abstract

Preparing chemically cross-linked collagenous biological graft material by preparation processes which include the step of altering the locations and/or orientations of chemical cross-linkages formed during the collagen cross-linking process. Embodiments of the method include various processes whereby physical force, stress or movement is applied to alter the relative positioning of the collagen fibers within the graft materials during at least the initial period of exposure to the collagen cross-linking reagent.

Claims

1. A method of preparing a flexible collagenous biological graft material comprising a network of collagen fibers, said method comprising the step of:

(a) longitudinally compressing the network of collagen fibers while exposing the collagen fibers to a collagen cross-linking reagent.

2. The method of claim 1 further comprising the steps of:

i. placing the graft material on a smooth surfaced support member;

ii. exerting a compressive force on said graft material to place said graft material in a longitudinally compressed state;

iii. maintaining the graft material in said compressed state;

iv. immersing the compressed graft material in the collagen cross-linking reagent for a period of time sufficient to effect adequate fixation of the collagen fibers within the graft material;

v. removing the graft material from the collagen cross-linking reagent; and

vi. removing the graft material from said compressed state and from the support member.

3. The method of claim 2 wherein step (ii.) further comprises:

compressing said graft material along its longitudinal axis to a compressed state so that the graft material is decreased in length by an amount equal to about 1% to 50% of its original length.

4. The method of claim 2 wherein step (ii.) further comprises:

compressing said graft material along its longitudinal axis to a compressed state so that the graft material is decreased in length by an amount equal to about 5% to 30% of its original length.

5. The method of claim 2 wherein step (iv.) comprises immersing the graft material in a liquid solution of polyepoxy fixative for at least 24 hours.

6. The method of claim 5 wherein "immersing the graft material in a liquid solution of polyepoxy fixative" comprises:

immersing the graft material in a 2% (vol.) aqueous solution of glycerol triglycidyl ether.

7. A collagenous biological vascular graft prepared by a method which comprises the steps of:

(a) harvesting a segment of blood vessel having a luminal surface and a network of collagen fibers from a mammalian source;

(b) placing the segment of blood vessel on a cylindrical support member having an outer surface such that the luminal surface of the blood vessel is in contact with the outer surface of the cylindrical support member;

(c) longitudinally compressing the segment of blood vessel to a compressed length so that the segment of blood vessel is shortened by an amount equal to 1% to 50% of its original relaxed length;

(d) immersing the longitudinally compressed segment of blood vessel in a collagen cross-linking reagent for a period of time sufficient to achieve adequate cross-linking of the collagen fibers contained in the segment of blood vessel;

(e) removing the segment of blood vessel from the collagen cross-linking reagent;

(f) releasing the segment of blood vessel from said longitudinally compressed state and removing the segment of blood vessel from the outer surface of said cylindrical support member.

8. The biological vascular graft of claim 7 wherein step (c) comprises:

longitudinally compressing the segment of blood vessel to a compressed length so that the segment of blood vessel is shortened by an amount equal to 40% to 50% of its original relaxed length.