Applications of advances in therapeutic electrical stimulation techniques and technologies in precision peripheral nerve repair: a narrative review

Peripheral nerve injuries affect large numbers of individuals each year, often resulting in long-term disabilities due to impairments in motor and sensory function. With traditional treatment approaches, including surgical repair and rehabilitation, the most common outcome is incomplete recovery. This is compounded by the absence of FDA-approved medications to enhance nerve regeneration. Recent advances in therapeutic electrical stimulation techniques have shown promise to improve axonal regrowth and functional recovery. Typically administered perioperatively in a single 1-hour session, therapeutic electrical stimulation has demonstrated efficacy in both preclinical studies and small clinical trials by promoting faster and more complete axonal regeneration. To address the limitations of traditional therapeutic electrical stimulation, including infection risks or lead displacement, the recent development of bioresorbable nerve stimulator implants has introduced a groundbreaking solution. Furthermore, patient-specific factors, including age, sex, medical comorbidities, and genetic variability, notably interact with clinical outcomes and potential responsiveness to therapeutic electrical stimulation. Such genes include the prevalent Val66Met genetic polymorphism in the brain-derived neurotrophic factor gene (rs6265). Carriers of rs6265 have less nerve regeneration, impaired activity-dependent brain-derived neurotrophic factor secretion, and a diminished response to therapeutic electrical stimulation in preclinical studies. This highlights the growing importance of tailoring therapeutic electrical stimulation protocols to each patient for optimal outcomes. The future of therapeutic electrical stimulation in the treatment of peripheral nerve injury will involve the integration of more sophisticated nerve stimulators to deliver tailored therapeutic electrical stimulation protocols, with careful consideration given to patient-specific factors and personalized rehabilitation strategies to maximize functional recovery.