Tiam Mana Saffari

17 GENERAL INTRODUCTION 1 The downside of processing is that it modifies the nerve, by removing Schwann cells, destroying neurotrophic factors and vascularity, resulting in an altered extracellular matrix with reduced regenerative potency 31,32 . Introduced in 2007, the Avance ® nerve graft was the first commercially available nerve allograft and combined pretreatments including chemical decellularization and gamma irradiation 33 . Their outcomes have demonstrated sufficient nerve regeneration over small distances not exceeding 3 cm, however, remain inferior to fresh autografts in large nerve defects 34-37 . Therefore, ongoing research has focused on augmentation of nerve allografts to enhance nerve regeneration. HISTORICAL BACKGROUND OF PERIPHERAL NERVE REGENERATION RESEARCH LINE Understanding of peripheral nerve injury and providing patient individualized nerve substitute to improve nerve regeneration in large nerve defects is an ongoing challenge for surgeons and nerve scientists. The goal is to enhance a decellularized nerve allograft to equal autograft performances in large nerve defects. Augmenting the nerve injury site of allografts to meet environmental advances of the autograft holds promise for enhancing nerve regeneration. This thesis is part of an ongoing research line with the Neural Regeneration Research Laboratory at Mayo Clinic, under supervision of Prof. Shin and Prof. Bishop, and builds on the results of previously conducted research that has focused on optimizing decellularized nerve allografts and seeding these allograft with stem cells. Optimizing nerve allograft decellularization Previously established pretreatment techniques of nerve allografts provided suboptimal results, especially with increasing gap distances 38 . Therefore, the primary approach in this research line focused on advancing decellularization techniques to better support nerve regeneration. Decellularization of a nerve allograft was successfully optimized by modifying previous processing protocols and adding elastase, an enzyme that significantly reduces the amount of axonal debris and immunogenicity, while maintaining ultrastructural properties. Furthermore, a comparisonwas performed between preservation conditions at 4 °C and -80 °C. Freeze- storage at -80 °C was found to damage the basal lamina structure, leading to impaired