PDGF/IGF-I In Peripheral Nerve Regeneration

Preliminary data have shown that a combination of insulin-like growth factor-I (IGF-I) andplatelet-derived growth factor (PDGF) acts synergistically to enhance the rate and quality of rats sciaticnerve regeneration. This project will investigate the optimal clinically acceptable carrier of IGF-I andPDGF, in combination, to enhance the regeneration of peripheral nerve across a gap. The investigatorsand others have used previously a commercially available cell culture material (Biomatrix I) as a carrierfor the growth factors impregnated into Biomatrix I have yielded impressive results, this tumor derivedcell cultured media cannot be used in human subjects and alternative vehicles must be tested if a humantherapeutic is to be developed. Consequently, two additional carriers, 1) methylcellulose, and 2) collagensolution, which have been used in unrelated, but approved human studies, will be investigated. Thethree carriers, each with and without the combination of PDGF and IGF-I, will be applied within silasticchambers 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 6and 12 weeks following surgery the function of the regenerated nerve will be assessed usingsomatosensory and motor evoked potentials. Quantitative histologic analysis of the regenerated sciaticnerves within the investigators will be optimize the dose of the combination of PDGF and IGF-I, initiatepotential alternative to the silastic chamber and conduct preclinical toxicology studies in preparation forhuman clinical trials.