Injury and regeneration of the peripheral nerve: Tissue engineering with contact guidance

Each year, there are approximately 800,000 peripheral nerve injuries that occur in the US, with an estimated 50,000 requiring surgical intervention. In many cases, a common injury mode is longitudinal stretch. Stretch can arise from mechanical deformation during trauma or may be induced iatrogenically via end to end anastomosis. Previous investigations into nerve electrophysiology during sustained stretch have demonstrated a decline in nerve conduction, although it was difficult to discern whether the functional deficits were due to ischemia, mechanical deformation or both. In this work, we elucidate the relationship between stretch magnitude and the degree of functional dysfunction and recovery using an ex vivo sciatic nerve model. Results demonstrate an inverse relationship between stretch magnitude and the degree of functional dysfunction and recovery. Correlation of the macro-level stretch to tissue-level strain revealed a highly heterogeneous strain field. This uneven strain distribution makes damage prediction difficult and emphasizes the need to minimize nerve stretch. In addition, a new scheme for an artificial peripheral nerve graft is introduced. The need for bridging devices in severely damaged peripheral nerves is evident as the current gold standard for nerve repair is the autologous graft. Complications associated with autografts include donor site morbidity, geometric mismatch, inconsistent functional outcome and the formation of neuromas. Using the concept of contact guidance, we hypothesize that structures encoded with directional guidance cues may facilitate the regeneration process in peripheral nerve. This approach was investigated using a combination of in vitro and in vivo techniques with two geometric schemes: (i) nano/micropatterned polymeric films; and (ii) microtubular polymeric arrays. These architectures were found to emulate the endogenous tissue anatomy while simultaneously providing directional information that enhances neurite extension, pathfinding and glia alignment in vitro. Preliminary in vivo studies of these implanted scaffolds show increased myelination and larger axon caliber compared to saline filled silicone controls. The combined data suggests contact guidance should be considered in potential clinical therapies