Multi-layered biomimetic material and method of formation

Patent metadata

Field	Value
Publication number	US-10695463-B2
Application number	US-201615758528-A
Country	US
Kind code	B2
Filing date	Sep 8, 2016
Priority date	Sep 8, 2015
Publication date	Jun 30, 2020
Grant date	Jun 30, 2020

Abstract

Biocompatible biomimetic materials that exhibit desirable mechanical properties while also encouraging cell ingrowth and proliferation are described. The biomaterials include a multi-layer laminate of three or more decellularized aligned collagen tissues. The individual layers are aligned with one another in an angle-ply arrangement, with the collagen of each layer aligned at an angle to the collagen of the adjacent layer. The biomaterials are useful as collagenous graft materials such as a patch for a hernia in an annulus fibrosus or grafting materials for repair of tendons, ligaments, cartilage and other musculoskeletal tissues.

First claim

What is claimed is:

1. A biocompatible multi-laminate, angle-ply construct comprising:
a first sheet including a first decellularized tissue, the first decellularized tissue including a first layer and a second layer, the first layer comprising collagen generally aligned in a first direction, the second layer comprising a multi-directional network of collagen fibers and elastin;
a second sheet including a second decellularized tissue, the second decellularized tissue including collagen generally aligned in a second direction, the first direction and the second direction defining an angle therebetween;
a third sheet including a third decellularized tissue, the third decellularized tissue including collagen generally aligned in a third direction, the third direction being essentially the same as the first direction, the second sheet being between the first sheet and the third sheet; wherein
the first, second and third sheets are attached to one another.

2. The biocompatible multi-laminate, angle-ply construct of claim 1 , wherein the angle is from about 25° to about 90°.

3. The biocompatible multi-laminate, angle-ply construct of claim 1 , wherein the angle is about 25° or less.

4. The biocompatible multi-laminate, angle-ply construct of claim 1 , wherein the second decellularized tissue comprises a first layer and a second layer, the first layer comprising collagen generally aligned in the second direction, the second layer comprising a multi-directional network of collagen fibers and elastin.

5. The biocompatible multi-laminate, angle-ply construct of claim 1 , wherein two or more of the first, second, and third decellularized tissues are derived from the same source tissue.

6. The biocompatible multi-laminate, angle-ply construct of claim 1 , wherein one or more of the first, second, and third decellularized tissues is decellularized pericardium.

7. The biocompatible multi-laminate, angle-ply construct of claim 1 , wherein one or more of the first, second, and third decellularized tissues are crosslinked.

8. The biocompatible multi-laminate, angle-ply construct of claim 1 , further comprising a hydrogel between at least the first and second sheet.

9. The biocompatible multi-laminate, angle-ply construct of claim 1 , wherein the biocompatible construct is an annulus fibrosus patch.

10. The biocompatible multi-laminate, angle-ply construct of claim 1 , wherein the biocompatible construct is a musculoskeletal graft.

11. The biocompatible multi-laminate, angle-ply construct of claim 1 , wherein the biocompatible construct exhibits a biaxial burst pressure of about 2 megapascals or greater, an ultimate tensile strength of about 3 megapascals or greater, and/or an elastic modulus of from about 12 megapascals to about 24 megapascals.

12. The biocompatible multi-laminate, angle-ply construct of claim 1 , wherein the third decellularized tissue comprises a first layer and a second layer, the first layer comprising collagen generally aligned in the third direction, the second layer comprising a multi-directional network of collagen fibers.

13. The biocompatible multi-laminate, angle-ply construct of claim 1 , the first sheet having an average thickness of between 150 micrometers and 270 micrometers.

14. A method for forming a biocompatible construct, the method comprising:
locating a first sheet adjacent to a second sheet, the first sheet including a first decellularized tissue, the first decellularized tissue including a first layer and a second layer, the first layer comprising collagen generally aligned in a first direction, the second layer comprising a multi-directional network of collagen fibers and elastin, the second sheet including a second decellularized tissue, the second decellularized tissue including collagen generally aligned in a second direction, the first sheet and the second sheet being located adjacent to one another such that an angle is defined between the first direction and the second direction;
locating a third sheet adjacent to the second sheet such that the second sheet is between the first sheet and the third sheet, the third sheet including a third decellularized tissue, the third decellularized tissue including collagen generally aligned in a third direction, the third sheet being located such that the third direction and the first direction are essentially the same; and
attaching the first, second, and third sheets to one another.

15. The method of claim 14 , the angle being from about 25° to about 90°.

16. The method of claim 14 , the angle being about 25° or less.

17. The method of claim 14 , further comprising decellularizing the first, second, and third tissues.

18. The method of claim 14 , further comprising crosslinking one or more of the first, second, and third decellularized tissues.

19. The method of claim 14 , wherein two or more of the first, second, and third decellularized tissues are derived from the same source tissue.

20. The method of claim 14 , wherein one or more of the first, second, and third decellularized tissues is decellularized pericardium.

21. The method of claim 14 , further comprising locating a hydrogel or a hydrogel precursor between at least the first and second sheets.

Assignees

• Univ Clemson
• Univ Clemson Res Foundation

Inventors

• Mcguire Rachel
• Borem Ryan
• Mercuri Jeremy

Classifications

• A61L27/50 Primary

  Materials characterised by their function or physical properties {, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials} · CPC title

• A61F2310/00371

  Collagen · CPC title

• A61F2002/4495

  having a fabric structure, e.g. made from wires or fibres · CPC title

• A61F2002/30009

  differing in fibre orientations · CPC title

• A61F2002/30971

  Laminates, i.e. layered products · CPC title