Biodegradable nerve guides

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.

1 . A nerve guide comprising a hollow body in the form of a tube having a wall with an external surface and an internal surface with defines a lumen, wherein the body comprises an outer biodegradable membrane, a hydrogel layer, and a nanofiber layer wherein the lumen is surrounded by the nanofiber layer. 
     
     
         2 - 23 . (canceled) 
     
     
         24 . A process for making a nerve guide comprising:
 grafting a hydrogel onto a biodegradable polymer membrane;   coating the hydrogel layer with a solution of neurotropic factors;   applying a nanofiber mesh to the hydrogel surface; and   forming the composition into a tube.   
     
     
         25 . The process of  claim 24 , wherein the biodegradable polymer membrane is formed by solvent casting, hot-pressing or stretching. 
     
     
         26 . The process of  claim 24 , wherein the grafting is thermal melt-mixing or solvent swelling. 
     
     
         27 . The process of  claim 24 , further comprising freeze-drying the neurotrophic factors in place. 
     
     
         28 . The process of  claim 24 , further comprising coating the hydrogel layer with a solution of neurotrophic factors after completion of the freeze drying. 
     
     
         29 . The process of  claim 28 , comprising freeze-drying and coating the hydrogel with a solution of neurotrophic factors multiple times. 
     
     
         30 . The process of  claim 29 , wherein the freeze-drying and coating steps are performed 2-15 times. 
     
     
         31 . The process of  claim 24 , wherein the neurotrophic factors are selected from the group consisting of NGF, BDNF, CNTF, GDNF, FGF, osteopontin, neublastin and neurturin. 
     
     
         32 . The process of  claim 31 , wherein at least two different neurotrophic factors are added to the nerve guide. 
     
     
         33 . The process of  claim 32 , wherein the neurotrophic factors are GDNF and BDNF. 
     
     
         34 . The process of  claim 32 , wherein the neurotrophic factors are GDNF and NT3. 
     
     
         35 . The process of  claim 24 , wherein the biodegradable membrane is selected from a group consisting of biodegradable polyesters, poly(amino acid)s or derivatives thereof, and natural biodegradable polymers. 
     
     
         36 . The process of  claim 24 , wherein the hydrogel layer is comprised of a material selected from the group consisting of PVA hydrogel or a mixture or PVA and one or more of pluronic polymers, heparin, heparan sulfate, chitosan, alginate, and dextran sulfate. 
     
     
         37 . The process of  claim 24 , wherein the nanofiber layer comprises one or more polymers selected from biodegradable polyesters, poly(amino acid)s and derivatives thereof. 
     
     
         38 . The process of  claim 24 , wherein the nanofiber layer comprises electrospun fibers. 
     
     
         39 . A method of treating peripheral nerve or spinal cord injury comprising:
 surgically implanting the nerve guide of  claim 1  at the site of a nerve injury;   thereby treating peripheral nerve or spinal cord injury.   
     
     
         40 . The method of  claim 39 , wherein the nerve guide comprises cells selected from autologous Schwann cells, Schwann cells derived from human pluripotent stem cells, and Schwann cells derived from adult stem cells. 
     
     
         41 . The method of  claim 40 , wherein the Schwann cells are derived from human induced pluripotent stem cells and human embryonic stem cells. 
     
     
         42 . The method of  claim 40 , wherein the Schwann cells are derived from allogenic or autologous mesenchymal stem cells.