Method of repairing perforated submucosal tissue graft constructs

• US 5,968,096 A
• Filed: 08/06/1997
• Issued: 10/19/1999
• Est. Priority Date: 04/05/1996
• Status: Expired due to Term

• Current Assignee: Clarian Health Partners, Inc.
• Original Assignee: Clarian Health Partners, Inc., Purdue Research Foundation (The Trustees of Purdue University (d/b/a Purdue University))
• Inventors: Whitson, Bryan, Badylak, Stephen F., Cheng, Boyle
• Primary Examiner(s): Yu, Mickey
• Assistant Examiner(s): Koh, Choon P.
• Application Number:
  US08/908,151
• Time in Patent Office: 804 Days
• Field of Search: 623/1, 623/11, 623/12, 623/16, 623/15, 424/422, 424/423, 424/424, 424/551
• US Class Current: 424/423
• CPC Class Codes: A61F 2/02 Prostheses implantable into the body closure means for urethra or rectum or for artificial body openings therefor A61F2/0004
• CPC Class Codes: A61F 2240/001 Designing or manufacturing processes
• CPC Class Codes: A61L 27/3629 Intestinal tissue, e.g. small intestinal submucosa
• 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

Abstract

A perforated unitary multi-laminar tissue graft construct and method for preparing such construct is described. The method comprises overlapping strips of submucosa tissue with other strips of submucosal tissue, compressing at least the overlapped portions of said strips between two surfaces under conditions that allow or promote dehydration of the compressed submucosa sheets, and perforating the resulting unitary tissue graft construct. The perforated tissue graft compositions have enhanced mechanical and remodeling properties relative to non-perforated submucosal tissue grafts.

Claims

1. In a method of preparing an improved unitary multilaminate tissue graft construct, said method comprising overlapping at least a portion of a strip of intestinal submucosa tissue with another strip of submucosa tissue, wherein the strips of submucosa tissue are delaminated from both the tunica muscularis and the luminal portion of the tunica mucosa of a warm blooded vertebrate;

and comprising at least the overlapped portions of the strips of submucosa tissue under conditions allowing at least partial dehydration of the compressed submucosa tissue;

the improvement comprising the step of perforating the overlapped portions of submucosa tissue to form perforations to decrease fluid retention in the graft and enhance the adhesion of adjacent layers.

2. The method of claim 1, wherein the perforations are uniformly distributed on the surfaces of the graft construct.

3. The method of claim 1, wherein the perforations in the submucosa tissue are prepared by pressing pins into the submucosa tissue.

4. The method of claim 3, wherein the pins are pressed into the submucosa tissue at an angle other than 90°

to the plane of the surface of the graft construct.

5. The method of claim 1, wherein the submucosa tissue has been dried to a water content of about 10%-20% by weight at the time the tissue is perforated.

6. The method of claim 1, wherein the strips of submucosa tissue forming said graft construct are orientated so that the graft construct has pseudoisotropic properties.

7. The method of claim 1, wherein the strips of submucosa are conditioned to have a strain of no more than 20%.

8. The method of claim 3, wherein the pins are pressed into the graft construct from two opposite sides of the multi-laminate tissue graft construct.

9. In a method of preparing an improved unitary multi-laminate tissue graft construct, said method comprising overlapping a portion of a strip of intestinal submucosa tissue with another strip of submucosa tissue, wherein each strip of submucosa tissue has first and second planar surfaces and each strip of submucosa tissue is delaminated from both the tunica muscularis and at least the luminal portion of the tunica mucosa of a warm blooded vertebrate, to form a graft construct having a planar surface with a surface area greater than the surface area of any one planar surface of the individual strips of submucosa tissue used to form said construct;

and compressing the overlapped portions of the strips of submucosa tissue under conditions allowing at least partial dehydration of the compressed submucosa tissue to form perforations;

the improvement comprising perforating the submucosa tissue to decrease fluid retention in the graft and enhance the adhesion of adjacent layers.

10. The method of claim 9, wherein the submucosa tissue has been dried to a water content of about 10%-20% by weight at the time the graft construct is perforated.

11. The method of claim 9, wherein the perforations are formed by pressing pins into the graft construct from two opposite sides of the multi-laminate tissue graft construct.

12. The method of claim 9, wherein the strips of submucosa tissue forming said graft construct are orientated so that the graft construct has pseudoisotropic properties.

13. In a method of preparing an improved unitary multi-laminate tissue graft construct, said method comprising overlapping at least a portion of a strip of intestinal submucosa tissue with another strip of submucosa tissue, wherein the strips of submucosa tissue are delaminated from both the tunica muscularis and at least the luminal portion of the tunica mucosa of a warm blooded vertebrate;

and compressing at least the overlapped portions of the strips of submucosa tissue under conditions allowing at least partial dehydration of the compressed submucosa tissue;

the improvement comprising perforating the overlapped portions of submucosa tissue wherein the perforated portion of the graft has at least 2 perforations per cm² to decrease fluid retention in the graft and enhance the adhesion of adjacent layers.

14. The method of claim 13, wherein the submucosa tissue has been dried to a water content of about 10%-20% by weight at the time the graft construct is perforated.

15. The method of claim 13, wherein the perforations are formed by pressing pins into the graft construct from two opposite sides of the multi-laminate tissue graft construct.

16. The method of claim 13, wherein the strips of submucosa tissue forming said graft construct are orientated so that the graft construct has pseudoisotropic properties.

17. The method of claim 13, wherein the perforations are formed by pressing pins into the graft construct at an angle other than 90°

to the plane of a surface of the graft construct.

18. The method of claim 13, wherein the perforations are uniformly distributed on the graft construct.