Mechanisms and outcomes of the supercharged end-to-side nerve transfer: a review of preclinical and clinical studies

Proximal peripheral nerve injuries often result in poor functional outcomes, chiefly because of the long time period between injury and the reinnervation of distal targets, which leads to muscle and Schwann cell atrophy. The supercharged end-to-side (SETS) nerve transfer is a recent technical innovation that introduces donor axons distally into the side of an injured nerve to rapidly innervate and support end organs while allowing for additional reinnervation after a proximal repair at the injury site. However, the mechanisms by which donor axons grow within the recipient nerve, contribute to muscle function, and impact the regeneration of native recipient axons are poorly understood. This uncertainty has slowed the transfer's clinical adoption. The primary objective of this article is to comprehensively review the mechanisms underpinning axonal regeneration and functional recovery after a SETS nerve transfer. A secondary objective is to report current clinical applications in the upper limb and their functional outcomes. The authors also propose directions for future research with the aim of maximizing the clinical utility of the SETS transfer for peripheral nerve surgeons and their patients.