Translational Approaches to Electrical Stimulation for Peripheral Nerve Regeneration

Background: Achieving functional repair after peripheral nerve injury (PNI) remains problematic despite considerable advances in surgical technique. Therein, questions lie regarding the variable capacity of peripheral nerves to regenerate based on environmental influence. In-depth analyses of multiple therapeutic strategies have ensued to overcome these natural obstacles. Of these candidate therapies, electrical stimulation has emerged a frontrunner. Extensive animal studies have reported the ability of brief intraoperative electrical stimulation (BES) to enhance functional regeneration after PNI. Despite these reports, the exact mechanisms by which BES enhances regeneration and its effects on long nerve lesions are largely unknown. Indeed, clinical translation of this seemingly simple therapeutic has not been so simple, but a few studies performed in humans have yielded highly encouraging results. Objective: We aimed to help bridge this translational gap by presenting the latest clinical trials on electrical stimulation for PNIs in combination with relevant etiologies, treatments and nonclinical findings. Methods: To do so, a systematic search was performed on PubMed, IEEE, and Web of Science databases up to February 2020 using keywords significant to our study. References of each manuscript were screened for additional manuscripts of relevance to our study. Results: We found multiple BES clinical studies reporting enhanced functional recovery or increased nerve regeneration. Although improved outcomes were reported, high variability after BES is seen between and within species likely due to injury severity, location and timeline along with other factors. Conclusion: Further clinical studies and introduction of novel delivery platforms are vital to uncover the true regenerative potential of electrical stimulation therapy.