A Shock to the (Nervous) System: Bioelectricity Within Peripheral Nerve Tissue Engineering.

The peripheral nervous system has the remarkable ability to regenerate in response to injury. However, this is only successful over shorter nerve gaps and often provides poor outcomes for patients. Currently, the gold standard of treatment is the surgical intervention of an autograft, whereby patient tissue is harvested and transplanted to bridge the nerve gap. Despite being the gold standard, more than half of patients have dissatisfactory functional recovery after an autograft. Peripheral nerve tissue engineering aims to create biomaterials that can therapeutically surpass the autograft. Current tissue-engineered constructs are designed to deliver a combination of therapeutic benefits to the regenerating nerve, such as supportive cells, alignment, extracellular matrix, soluble factors, immunosuppressants, and other therapies. An emerging therapeutic opportunity in nerve tissue engineering is the use of electrical stimulation (ES) to modify and enhance cell function. ES has been shown to positively affect four key cell types, such as neurons, endothelial cells, macrophages, and Schwann cells, involved in peripheral nerve repair. Changes elicited include faster neurite extension, cellular alignment, and changes in cell phenotype associated with improved regeneration and functional recovery. This review considers the relevant modes of administration and cellular responses that could underpin incorporation of ES into nerve tissue engineering strategies. Impact Statement Tissue engineering is becoming increasingly complex, with multiple therapeutic modalities often included within the final tissue-engineered construct. Electrical stimulation (ES) is emerging as a viable therapeutic intervention to be included within peripheral nerve tissue engineering strategies; however, to date, there have been no review articles that collate the information regarding the effects of ES on key cell within peripheral nerve injury. This review article aims to inform the field on the different therapeutic effects that may be achieved by using ES and how they may become incorporated into existing strategies.