Composite neural conduit

Abstract

A composite nerve conduit comprising an elongated body comprising one or more hollow elongated internal channels for guiding and promoting nerve regeneration. The conduit is a three-dimensional scaffold comprising a crosslinked hybrid/composite matrix of collagen and soy protein isolate having improved mechanical and biocompatibility properties. Methods of using the conduit for promoting nerve regeneration at a site of neural tissue damage by bridging wounded, severed, or damaged nerve sections in a peripheral and/or central nervous system. Methods of fabricating composite neural conduits are also disclosed.

1 . A composite nerve conduit comprising an elongated body comprising one or more hollow elongated internal channels for guiding and promoting nerve regeneration, said one or more hollow elongated internal channels defined by a sidewall comprising a crosslinked composite matrix of collagen and soy protein isolate, said body having respective first and second terminal ends, wherein said one or more internal channels extends between the first and second ends of the conduit body. 
     
     
         2 . The composite nerve conduit of  claim 1 , comprising two or more of said hollow elongated internal channels for guiding and promoting nerve regeneration. 
     
     
         3 . The composite nerve conduit of  claim 1 , said body having cross-sectional dimension of from about 1 mm to about 4 cm and a length of from about 5 mm to about 100 mm. 
     
     
         4 . The composite nerve conduit of  claim 1 , wherein the neural conduit is configured to substantially encircle at least two damaged neural sections in a peripheral and/or central nervous system and bridge any gap therebetween. 
     
     
         5 . The composite nerve conduit of  claim 1 , wherein said neural conduit comprises one or more additional elements selected from the group consisting of growth factors, stem cells, neural cells, progenitor cells, gene vectors, proteins, therapeutic peptides, siRNA, miRNA, chemical compounds, and combinations thereof adsorbed thereon or therein. 
     
     
         6 . The composite nerve conduit of  claim 1 , said one or more hollow elongated internal channels is filled with a hydrogel comprising at least one material selected from the group consisting of a collagen/soy protein composite, chitin, chitosan, guar gum, gum karaya, agar, treated agar, fenugreek seed mucilage, soy polysaccharide, gellan gum, mango peel pectin, lepidium sativum mucilage, plantago ovata seed mucilage, aegle marmelos gum, locust bean gum, ficus indica fruit mucilage,  Mangifera indica  gum, hibiscus rosa sinesis mucilage and treated agar, dehydrated banana powder, collagen, fibrin, fibronectin, laminin, hyaluronic acid, polysilozane, polyphosphazene, low-density polyethylene, high-density polyethylene, plastic, polypropylene, polyvinyl chloride, polystyrene, nylon, nylon-6, nylon-66, Teflon thermoplastic polyurethanes, polylacticoglycolic acid, polycaprolactone, and combinations thereof. 
     
     
         7 . The composite nerve conduit of  claim 1 , said sidewall consisting essentially of said crosslinked composite matrix of collagen and soy protein isolate. 
     
     
         8 . The composite nerve conduit of  claim 1 , wherein said soy protein isolate is high in genistein. 
     
     
         9 . The composite nerve conduit of  claim 1 , wherein said composite comprises a weight ratio of collagen and soy protein isolate of from about 20:80 to about 80:20. 
     
     
         10 . The composite nerve conduit of  claim 1 , wherein said collagen is type I collagen. 
     
     
         11 . A method of promoting nerve regeneration at a site of neural tissue damage by bridging wounded, severed, or damaged nerve sections in a peripheral and/or central nervous system, said method comprising contacting one damaged nerve end with a first end of a composite neural conduit according to  claim 1 , and contacting a second end of the neural conduit with an opposing damaged nerve end. 
     
     
         12 . The method of  claim 11 , further comprising applying an electric current to said site of neural tissue damage. 
     
     
         13 . The method of  claim 12 , wherein said electric current is configured to generate a unidirectional electric field at said site of nerve tissue damage from one damaged nerve end to the opposing damaged nerve end. 
     
     
         14 . A method of fabricating a composite neural conduit, said method comprising:
 providing a biopolymer solution comprising collagen and soy protein isolate dissolved or dispersed in a solvent system;   applying said biopolymer solution to a negative mold to form the body of the conduit, said mold including a plurality of elongated removable inserts for forming one or more hollow elongated internal channels within the body,   solidifying the biopolymer solution to yield a crosslinked matrix comprising a composite of collagen and soy protein isolate; and   removing said crosslinked matrix from said mold to yield an elongated body comprising the one or more hollow elongated internal channels extending between respective terminal ends of the body.   
     
     
         15 . The method of  claim 14 , wherein said biopolymer solution consists of said collagen and soy protein isolate dissolved or dispersed in said solvent system. 
     
     
         16 . The method of  claim 14 , wherein said solidifying the biopolymer comprises crosslinking collagen and soy protein isolate to yield said crosslinked matrix. 
     
     
         17 . The method of  claim 16 , wherein said crosslinking comprises adding one or more crosslinking agents to the biopolymer solution. 
     
     
         18 . The method of  claim 17 , wherein said crosslinking agents are selected from the group consisting of 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) and N-hydroxysuccinimide (NHS), transglutaminase, glutaraldehyde, sulfonates, genipin, and combinations thereof. 
     
     
         19 . The method of  claim 17 , further comprising washing said crosslinked matrix to remove residual crosslinker. 
     
     
         20 . The method of  claim 14 , further comprising lyophilizing said crosslinked matrix before removing from the mold.