The Physiologic Basis of Molecular Therapeutics for Peripheral Nerve Injury: A Primer

Peripheral nerve injuries affect a significant number of patients who experience trauma affecting the hand and upper extremity. Improving unsatisfactory outcomes from repair of these injuries remains a clinical challenge despite advancements in microsurgical repair. Imperfections of the nerve regeneration process, including imprecise reinnervation, distal axon degradation, and muscular atrophy, complicate the repair process. However, the capacity for peripheral nerves to regenerate offers an avenue for therapeutic advancement. Regeneration is a temporally and spatially dynamic process coordinated by Schwann cells and neurons among other cell types. Neurotrophic factors are a primary means of controlling cell growth and differentiation in the repair setting. Sustained axon survival and regrowth and consequently functional outcomes of nerve repair in animal models are improved by the administration of neurotrophic factors, including glial cell-derived neurotrophic factor, nerve growth factor, sterile alpha and TIR motif containing 1, and erythropoietin. Targeted and sustained delivery of neurotrophic factors through gelatin-based nerve conduits, multiluminal conduits, and hydrogels have been shown to enhance the innate roles of these factors to promote expedient and accurate peripheral nerve regeneration in animal models. These delivery methods may help address the practical limitations to clinical use of neurotrophic factors, including systemic side effects and the need for carefully timed, precisely localized release schedules. In addition, tacrolimus has also improved peripheral nerve regrowth in animal models and has recently shown promise in addressing human disease. Ultimately, this realm of adjunct pharmacotherapies provides ample promise to improve patient outcomes and advance the field of peripheral nerve repair.