Biodegradable nerve guides

Patent metadata

Field	Value
Publication number	US-9707000-B2
Application number	US-201314081381-A
Country	US
Kind code	B2
Filing date	Nov 15, 2013
Priority date	Jan 25, 2008
Publication date	Jul 18, 2017
Grant date	Jul 18, 2017

Abstract

The present invention is directed to the compositions and methods of preparing hydrogel-grafted nerve guides for peripheral nerve regeneration. Particularly, the present invention describes the nerve guides and methods for preparation of hydrogel-grafted nerve guides with encapsulated neurotrophic factors and a nanofiber mesh lining the inner surface of the guide. The present invention also provides methods for peripheral nerve repair using these hydrogel-grafted nerve guides.

First claim

What is claimed is:

1. A nerve guide for peripheral nerve regeneration comprising:
an outer biodegradable poly(ε-caprolactone) (PCL) membrane which forms an external surface of a hollow body in the form of a tube;
a cross-linked hydrogel layer comprising polyvinyl alcohol (PVA) and poly(ethylene glycol) (PEG) in an IPN network comprising glial cell-derived neurotrophic factor (GDNF), wherein an external surface of the cross-linked hydrogel layer is coupled to an internal surface of the outer biodegradable PCL membrane; and a surface-functionalized nanofiber layer comprising electrospun fibers and a surface-tethered laminin coating, and wherein the surface-functionalized nanofiber layer is coupled to an internal surface of the cross-linked hydrogel layer to form an internal surface that defines a lumen of the hollow body.

2. The nerve guide of claim 1 , wherein the cross-linked hydrogel layer comprises GDNF and BDNF or GDNF and NT3.

3. The nerve guide of claim 1 , wherein the surface-functionalized nanofiber layer is further coated with heparin.

4. The nerve guide of claim 1 , wherein the nanofiber layer comprises laminin and heparin.

5. The nerve guide of claim 1 , wherein the outer biodegradable PCL membrane is between about 50 and about 1000 μm thick.

6. The nerve guide of claim 1 , wherein the outer biodegradable PCL membrane is porous.

7. The nerve guide of claim 1 , wherein the cross-linked hydrogel layer further comprises a pluronic polymer, heparin, heparan sulfate, chitosan, alginate, or dextran sulfate.

8. The nerve guide of claim 1 , wherein a thickness of the cross-linked hydrogel layer is between about 200 μm and about 1.5 mm in a swollen state.

9. The nerve guide of claim 1 , wherein the surface functionalized nanofiber layer comprises one or more natural or synthetic biocompatible polymers comprising polymer fibers selected from the group consisting of biodegradable polyesters, proteins, and polysaccharides.

10. The nerve guide of claim 9 , wherein the one or more polymer fibers comprise a polyester or derivative thereof.

11. The nerve guide of claim 9 , wherein the polymer fibers comprise collagen or laminin.

12. The nerve guide of claim 9 , wherein the one or more polymer fibers comprise chondroitin sulfate, alginate or derivatives thereof.

13. The nerve guide of claim 9 , wherein the one or more polymer fibers comprise polylactide, polyglycolide, polycaprolactone or copolymers thereof.

14. The nerve guide of claim 9 , wherein an average fiber diameter is between about 10 nm and 10 μm.

15. The nerve guide of claim 9 , wherein an average fiber diameter is between about 100 nm and 1 μm.

16. The nerve guide of claim 1 , wherein the electrospun fibers are randomly oriented fibers.

17. The nerve guide of claim 1 , wherein the electrospun fibers are aligned fibers.

18. The nerve guide of claim 1 , wherein the GDNF is present in a gradient of lower concentration to higher concentration from a proximal end of the nerve guide to a distal end of the nerve guide.

19. The nerve guide of claim 1 , wherein the nanofiber layer further comprises a Schwann cell.

20. A method of treating peripheral nerve or spinal cord injury comprising: surgically implanting the nerve guide of any one of claims 1 , 2 , 3 , 4 , 5 - 13 , 16 - 18 or 19 at a site of a nerve injury; thereby treating peripheral nerve or spinal cord injury.

21. The method of claim 20 , wherein the nerve guide comprises cells selected from the group consisting of autologous Schwann cells, Schwann cells derived from human pluripotent stem cells, and Schwann cells derived from adult stem cells.

22. The method of claim 21 , wherein the Schwann cells are derived from human induced pluripotent stem cells or human embryonic stem cells.

23. The method of claim 21 , wherein the Schwann cells are derived from allogenic or autologous mesenchymal stem cells.

Assignees

• Univ Johns Hopkins

Inventors

• Hoke Ahmet
• Lim Shawn H
• Liu Xingyu
• Mao Hai-Quan

Classifications

• A61L27/383

  Nerve cells, e.g. dendritic cells, Schwann cells · CPC title

• A61L27/56

  Porous materials, {e.g. foams or sponges} · CPC title

• A61L2400/12

  Nanosized materials, e.g. nanofibres, nanoparticles, nanowires, nanotubes; Nanostructured surfaces · CPC title

• A61L27/3878

  Nerve tissue, brain, spinal cord, nerves, dura mater · CPC title

• A61L2430/32

  for nerve reconstruction · CPC title