Peripheral nerve regeneration by synthetic peptide nanofibers

Abstract

The peripheral nervous system (PNS) has a complex structure that consists of high numbers of nerve cells and communication networks between the central nervous system and the body parts. Unlike the central nervous system, the PNS exhibits a considerable capacity for regeneration; however, peripheral nerve injuries can nevertheless cause lifelong disability. Various methods are currently available for the treatment of nerve injuries, but autologous nerve grafting is considered as ‘the gold standard’. Donor site morbidity, neuroma formation and failure of functional recovery are some limitations of this technique, especially when used for the repair of long nerve gaps. Polymeric nerve conduits are clinically available alternatives to nerve grafting, and function by guiding the axonal growth and isolating the regenerating axon from the inhibitory environment present in the post-injury neuroma. In this thesis, we used peptide amphiphile molecules (PAs) that can self-assemble into the nanofibers and mimic both the structure and function of healthy ECM of nerve cells for sciatic nerve regeneration. Two bioactive PAs, LN-PA (derived from laminin) and GAG-PA (derived from glycosaminoglycan), were tested for their ability to induce neural regeneration in a rat sciatic nerve model. Hollow nerve conduits were filled with peptide nanofiber gels, and electrophysiology and histology results were compared with autologous graft treated groups. Our results show that bioactive peptide nanofibers are able to boost regeneration and functional motor and sensory recovery. Electromyography results demonstrated that better signal transmission was observed in peptide nanofiber treated groups compared with empty conduits and autograft treated groups. Histological assessments also confirmed that bioactive peptide nanofiber treated groups exhibited better axonal regeneration. These results suggest that these biologically active PA nanofiber gels may be used as a biomaterial for peripheral nerve regeneration in clinical practice.