Multilayered submucosal graft constructs and method for making the same

• US 5,955,110 A
• Filed: 11/12/1996
• Issued: 09/21/1999
• Est. Priority Date: 04/07/1995
• Status: Expired due to Term

• Current Assignee: Clarian Health Partners, Inc., Methodist Hospitals of Dallas
• Original Assignee: Methodist Hospitals of Dallas, Purdue Research Foundation (The Trustees of Purdue University (d/b/a Purdue University))
• Inventors: Cheng, Boyle, Whitson, Bryan A., Patel, Umesh H., Hiles, Michael C., Badylak, Stephen F., Kokini, Klod
• Primary Examiner(s): Witz, Jean C.
• Application Number:
  US08/776,490
• Time in Patent Office: 1,043 Days
• Field of Search: 424/551, 623/11, 623/13
• US Class Current: 424/551
• CPC Class Codes: A61F 2/0063 Implantable repair or support meshes, e.g. hernia meshes
• CPC Class Codes: A61K 35/38 Stomach; Intestine; Goblet cells; Oral mucosa; Saliva
• CPC Class Codes: A61L 27/3629 Intestinal tissue, e.g. small intestinal submucosa
• CPC Class Codes: A61L 27/3691 characterised by physical conditions of the treatment, e.g. applying a compressive force to the composition, pressure cycles, ultrasonic/sonication or microwave treatment, lyophilisation
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

Multi-laminar tissue graft constructs, pseudoisotropic graft constructs and a method of preparing such constructs are described. Multi-laminar tissue graft constructs are prepared by fusing partially overlapped strips of submucosa tissue into a unitary graft construct by compressing the tissue under dehydrating conditions. Pseudoisotropic tissue graft constructs are prepared by overlapping a first strip of submucosa tissue with at least two strips of submucosa tissue orientated so that the longitudinal axis of each strip formts an angle of about 180°/N with the longitudinal axes of at least two other strips of submucosal tissue.

Claims

1. A method of preparing a multi-laminate tissue graft construct having pseudoisotropic properties, said construct formed from at least three strips of intestinal submucosal tissue delaminated from both the tunica muscularis and at least the luminal portion of the tunica mucosa of a wanm blooded vertebrate, each strip of intestinal submucosal tissue having a longitudinal axis corresponding to the predominant orientation of the collagen fibers in the submucosal tissue strips, said method comprising the steps of

overlaying said first strip with at least two additional strips of submucosal tissue so that the longitudinal axis of each individual strip of submucosal tissue forms an angle of about 180°

/N with the longitudinal axes of two other strips of overlaid submucosal tissue, wherein N=the total number of strips of submucosal tissue;

compressing at least the overlapped portions of the strips of submucosal tissue between two surfaces under conditions allowing at least partial dehydration of the compressed submucosal tissue.

2. The method of claim 1, wherein at least one of the surfaces is water permeable.

3. The method of claim 1, further comprising the step of applying a vacuum to the subrnucosal tissue during compression thereof.

4. The method of claim 3, wherein the applied vacuum coacts with the two surfaces to compress the submucosal tissue.

5. The method of claim 1, further comprising the step of applying heat to the submucosal tissue during compression thereof.

6. The method of claim 1, wherein the two surfaces are complementary nonplanar surfaces wherein compression between the two surfaces produces a tissue graft construct shaped to conform to those surfaces.

7. A unitary pseudoisotropic multi-laminate tissue graft construct, comprising at least three strips of intestinal submucosal tissue delaminated from both the tunica muscularis and at least the luminal portion of the tunica mucosa of a warm blooded vertebrate, wherein the strips are fused to one another by compressing the strips under dehydrating conditions, each strip having a longitudinal axis corresponding to the predominant orientation of the collagen fibers in the strips, wherein the longitudinal axis of each strip forms an angle of about 180°

/N with the longitudinal axes of two other strips forming said construct, wherein N=the total number of strips of submucosal tissue.

8. The method of claim 7, wherein the strips of intestinal submucosal tissue consist essentially of the tunica submucosa, the muscularis mucosa and the stratum compactum of the tunica mucosa.

9. The tissue graft construct of claim 7, wherein the intestinal submucosal tissueis conditioned to have a strain of no more than 20%.

18. The method of claim 7, wherein the strips of intestinal submucosal tissue consist essentially of the tunica submucosa, the muscularis mucosa and the stratum compactum of the tunica mucosa.

10. A method of preparing a multi-laminate tissue graft construct from multiple strips of intestinal submucosal tissue delaminated from both the tunica muscularis and at least the luminal portion of the tunica mucosa of a warm blooded vertebrate, said strips having an abluminal surface and a luminal surface, said method comprising the steps of

placing a first strip of submucosal tissue on a support, so the luminal surface of the strip of submucosal tissue is in contact with the support;

overlaying said first strip with additional strips of submucosal tissue wherein the last strip of submucosal tissue layered onto the tissue graft construct is orientated so the abluminal surface is in contact with the other layers of submucosal tissue forming the tissue graft construct;

compressing the overlapped portions of the strips of submucosal tissue between two surfaces under conditions allowing at least partial dehydration of the compressed submucosal tissue.

11. The tissue graft construct of claim 10, wherein the strips of intestinal submucosal tissueconsist essentially of the tunica submucosa, the muscularis mucosa and the stratum compactum of the tunica mucosa.

12. The method of claim 10, wherein at least one of the surfaces is water permeable.

13. The method of claim 10, further comprising the step of applying a vacuum to the submucosal tissue during compression thereof.

14. The method of claim 13, formed as a unitary heterolaminar graft construct.

15. The method of claim 13, formed as a unitary homolaminar graft construct.

16. The method of claim 13, formed as a pseudoisotropic graft construct.

17. The graft construct of claim 16, formed as a unitary heterolaminar graft construct.

19. The graft construct of claim 16, formed as a pseudoisotropic graft construct.

23. The method of claim 17, formed as a pseudoisotropic graft construct.

20. A method of preparing a multi-laminate tissue graft construct from multiple strips of intestinal submucosal tissue delaminated from both the tunica muscularis and at least the luminal portion of the tunica mucosa of a warm blooded vertebrate, said strips having an abluminal surface and a luminal surface, said method comprising the steps of

placing a first strip of submucosal tissue on a support, so the luminal surface of the strip of submucosal tissue is in contact with the support;

overlaying said first strip with a second strip of submucosal tissue to form a multi-layered construct, said second strip orientated so that the luminal surface of the second strip contacts at least a portion of the abluminal surface of the first strip;

overlaying an additional strip of submucosal tissue onto said multi-layered construct, wherein said additional strips is overlaid with its abluminal surface in contact with at least a portion of abluminal surface of the multi-layered graft construct;

compressing the overlapped portions of the strips of submucosal tissue between two surfaces under conditions allowing at least partial dehydration of the compressed submucosal tissue.

21. The tissue graft construct of claim 20, wherein the strips of intestinal submucosal tissueconsist essentially of the tunica submucosa, the muscularis mucosa and the stratum compactum of the tunica mucosa.

22. The method of claim 20, wherein at least one of the surfaces is water permeable.

24. The method of claim 20, further comprising the step of applying heat to the submucosal tissue during compression thereof.

25. The method of claim 20, wherein the two surfaces are complementary nonplanar surfaces wherein compression between the two surfaces produces a tissue graft construct shaped to conform to those surfaces.

26. The graft construct of claim 20, formed as a pseudoisotropic graft construct.