Purpose: Proximal nerve injuries present significant challenges due to the distance between the injury site and neuromuscular junctions (NMJs). Axonal regeneration after proximal nerve repair often leads to prolonged muscle denervation, resulting in irreversible motor endplate degeneration and fibrosis, ultimately compromising functional recovery. In severe cases, such as pan-brachial plexus injuries, nerve grafts or transfers may restore partial hand function but fail to reinnervate intrinsic muscles critical for precision.To address these challenges, the muscle cuff regenerative peripheral nerve interface (MC-RPNI) was developed as a bridge for robotic exoskeleton control. This novel interface uses a free skeletal muscle graft wrapped around an intact peripheral nerve. The graft undergoes robust regeneration, while the nerve sprouts collaterally to reinnervate the muscle, amplifying motor action potentials and improving the signal-to-noise ratio (SNR). This enhanced signal fidelity enables precise capture of motor intention. The MC-RPNI is particularly effective for proximal nerve injuries, where delayed regeneration often leads to muscle denervation. Its primary goal is to relay and amplify signals from viable regenerating axons, transforming them into outputs capable of driving robotic exoskeletons. This innovative approach holds promise for restoring function in severe nerve injuries.

Method:
This is a 3-year protocol focusing on the C8-T1 roots of the rat brachial plexus as the primary surgical site, with the median nerve and downstream forearm flexor muscles serving as the target for outcome evaluations. In the first year, the goal is to establish a reliable proximal injury model with consistently poor outcomes in the target muscles. Three types of proximal injuries will be created at the root level to identify a model that consistently yields poor functional recovery. Behavioral tests, electrophysiological studies, and immunohistochemical analyses will be used to validate the outcomes. In the second year, the objective is to assess the signaling capabilities and viability of the MC-RPNI in a proximal cut-and-repair model. A muscle graft will be wrapped around the distal end of the coaptation site, either at the lower trunk or median nerve level, to evaluate its ability to capture signals from the reinnervated nerve. Additionally, the impact of the muscle graft on the function of distal target muscles will be assessed. In the third year, the focus will shift to the MC-RPNI’s signal amplification capabilities in a delayed proximal nerve injury model. The aim is to determine whether the timing of reconstruction affects the graft’s ability to amplify nerve signals. The muscle graft will be positioned around the distal lower trunk or median nerve to evaluate its efficacy in capturing signals from a reinnervated nerve after delayed repair.