Growth factor enhancement of peripheral nerve regeneration through a novel synthetic hydrogel tube.
OBJECTIVE
The authors' long-term goal is repair of peripheral nerve injuries by using synthetic nerve guidance devices that improve both regeneration and functional outcome relative to an autograft. They report the in vitro processing and in vivo application of synthetic hydrogel tubes that are filled with collagen gel impregnated with growth factors.


METHODS
Poly(2-hydroxyethyl methacrylate-co-methyl methacrylate) (PHEMA-MMA) porous 12-mm-long tubes with an inner diameter of 1.3 mm and an outer diameter of 1.8 mm were used to repair surgically created 10-mm gaps in the rat sciatic nerve. The inner lumen of the tubes was filled with collagen matrix alone or matrix supplemented with either neurotropin-3 at 1 microg/ml, brain-derived neurotrophic factor at 1 microg/ml, or acidic fibroblast growth factor (FGF-1) at 1 or 10 microg/ml. Nerve regeneration through the growth factor-enhanced tubes was assessed at 8 weeks after repair by histomorphometric analysis at the midgraft level and in the nerve distal to the tube repair. The tubes were biostable and biocompatible, and supported nerve regeneration in more than 90% of cases. Nerve regeneration was improved in tubes in which growth factors were added, compared with empty tubes and those containing collagen gel alone (negative controls). Tubes filled with 10 microg/ml of FGF-1 dispersed in collagen demonstrated regeneration comparable to autografts (positive controls) and showed significantly better regeneration than the other groups.


CONCLUSIONS
The PHEMA-MMA tubes augmented with FGF-1 in their lumens appear to be a promising alternative to autografts for repair of nerve injuries. Studies are in progress to assess the long-term biocompatibility of these implants and to enhance regeneration further.
Midha
Rajiv
R
Division of Neurosurgery and Neuroscience Research Program, Sunnybrook & Women's College Health Sciences Centre, Toronto, Ontario, Canada. Rajiv.midha@swchsc.on.ca
Munro
Catherine A
CA
Dalton
Paul D
PD
Tator
Charles H
CH
Shoichet
Molly S
MS
D000818:Animals; D001672:Biocompatible Materials / Q000627:therapeutic use*; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology; D016220:Fibroblast Growth Factor 1 / Q000494:pharmacology*; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000627:therapeutic use*; D008297:Male; D023421:Models, Animal; D009416:Nerve Regeneration / Q000187:drug effects* / Q000502:physiology; D020933:Neurotrophin 3 / Q000494:pharmacology; D019736:Prostheses and Implants; D051381:Rats; D011917:Rats, Inbred Lew; D012584:Sciatic Nerve / Q000187:drug effects* / Q000502:physiology
D001672:Biocompatible Materials; D019208:Brain-Derived Neurotrophic Factor; D020933:Neurotrophin 3; D016220:Fibroblast Growth Factor 1; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate