Biologic Strategies to Improve Nerve Regeneration after Peripheral Nerve Repair

Traumatic peripheral nerve injuries affect 350,000 patients per year,1 accounting for $150 billion in annual health care costs.2 Direct nerve repair is the gold standard, however, surgeons often find a gap that prevents a tension-free direct repair. Autograft appears to be the ideal choice for bridging these gaps, but it is associated with donor site morbidity and has limited availability.2 There have been multiple recent reviews detailing a variety of conduit and allograft options for reconstruction.3–9 Successful reconstruction of a nerve gap requires a scaffold, vascular ingrowth, fibroblasts, and Schwann cells.10 The ideal scaffold would have a microstruc-ture to guide regenerating axons and secrete growth factors and local signaling factors. Nerve autograft allows revascu-larization within 48 to 72 hours because of existing vascular networks, compared with greater than 7 days for conduits and allograft.11 Despite our best efforts, nerve repair has resulted in suboptimal clinical results. The purpose of this article is to review the current strate-gies for augmenting nerve repair, including the use of nerve conduits, neurotrophic factors, Schwann cells, and stem cell therapies. Nerve Conduits (Tubulization) The donor site morbidity and limited availability of nerve autograft has led to the development or alternative methods to bridge nerve gaps that are unable to be directly repaired. Although early attempts at bridging nerve gaps were firs