Preliminary data have shown that a combination of insulin-like growth factor-I (IGF-I) and platelet-derived growth factor (PDGF) acts synergistically to enhance the rate and quality of rats sciatic nerve regeneration. This project will investigate the optimal clinically acceptable carrier of IGF-I and PDGF, in combination, to enhance the regeneration of peripheral nerve across a gap. The investigators and others have used previously a commercially available cell culture material (Biomatrix I) as a carrier for the growth factors impregnated into Biomatrix I have yielded impressive results, this tumor derived cell cultured media cannot be used in human subjects and alternative vehicles must be tested if a human therapeutic is to be developed. Consequently, two additional carriers, 1) methylcellulose, and 2) collagen solution, which have been used in unrelated, but approved human studies, will be investigated. The three carriers, each with and without the combination of PDGF and IGF-I, will be applied within silastic chambers at the time of wounding. A silastic chamber, 8.0mm segmental sciatic nerve defect model, will be used. Before surgery. and weekly, gait will be analyzed using a walking toe print index. At 6 and 12 weeks following surgery the function of the regenerated nerve will be assessed using somatosensory and motor evoked potentials. Quantitative histologic analysis of the regenerated sciatic nerves within the investigators will be optimize the dose of the combination of PDGF and IGF-I, initiate potential alternative to the silastic chamber and conduct preclinical toxicology studies in preparation for human clinical trials.
