Sciatic Nerve Regeneration in RGD-conjugated-Aligned-Nanofiber Conduits

Introduction: Peripheral segmental nerve injuries are most commonly treated with nerve autografting. However, the availability of autograft tissue is limited, and the morbidity of graft harvesting is significant. As potential alternatives, artificial grafts have been made from natural and synthetic polymers. However, currently available synthetic conduits yield inferior results compared to autografts. The incorporation of physical guidance and biochemical factors such as extracellular matrix (ECM) proteins and neurotrophins may promote axonal regeneration, and improve the performance of nerve conduits. RGD (Arg-Gly-Asp tripeptide) is a moiety found in several adhesive ECM molecules. As a central binding domain of fibronectin, it has been shown to play an essential role during adult axonal outgrowth, via RGD/fibronectin-integrin interactions (1). We have synthesized biodegradable-alignednanofiber scaffolds covalently conjugated with RGD-peptides. Our previous studies have shown that the presence of unidirectional nanofiber alignment and RGD-peptide moeity significantly enhances axonal outgrowth in mice Dorsal Root Ganglia explant cultures. In this study, we investigated the effectiveness of RGD-conjugated-aligned nanofiber conduits in repairing a 10mm segmental sciatic nerve injury in rats. The extent of nerve regeneration was evaluated by nerve conduction velocity and histological analysis at 6 weeks and 12 weeks post surgery.