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Updated: Jan 11, 2026

The Muscle Cuff Regenerative Peripheral Nerve Interface for the Amplification of Intact Peripheral Nerve Signals
Published on: January 13, 2022
Optimizing Neuromuscular Junction Formation for Enhanced Signal Transduction in the Regenerative Peripheral Nerve
Ken Kuan-Wei Chen1, Paul S Cederna2, Yu-Han Huang1
1From the Department of Plastic and Reconstructive Surgery, Chang Gung Memorial Hospital, and Chang Gung University.
Background:
Regenerative peripheral nerve interface (RPNI) surgery amplifies the motor intent from upstream peripheral nerves, enabling myoelectric prosthetic devices to better capture signals, thereby improving the precision of prosthetic limb control. This study aimed to clarify the mechanisms underlying RPNI motor function through neuromuscular junction (NMJ) evaluation and provide a novel method of enhancing reinnervation to improve signal amplification.
Methods:
Adult wild-type C57BL/6J mice underwent RPNI surgery using free extensor digitorum longus (EDL) muscle grafts transferred to the thigh and neurotized with the common peroneal nerve (CPN) in 3 ways: RPNI:CPN neurotization; separation of double fascicular RPNI:CPN into 2 fascicles, followed by neurotization; and denervation of the RPNI without CPN neurotization. In the control groups, the EDL muscles remained in situ with intact CPN innervation (healthy EDL) or cut and repaired CPN. The end point assessments were conducted at 8 weeks and 12 weeks postoperatively with electrodiagnostic tests, target muscle weight measurement, whole-mount immunofluorescence staining, and Western blot analysis.
Results:
The results showed that the RPNI demonstrates adequate NMJ innervation for effective neural signal amplification. Double fascicular RPNI exhibited greater compound muscle action potential, larger target muscle weight, a greater number of reinnervated NMJs, and reduced motor endplate fragmentation compared with RPNI.
Conclusions:
The degree of NMJ reinnervation and the morphology of the motor endplate within the RPNI reveal information about the innervation. Dividing the neural source enhances NMJ reinnervation within the RPNI, with the added potential of improving signal amplification.
Clinical Relevance Statement:
By studying NMJ innervation, the authors have gained an understanding of the signal transduction mechanisms of RPNI. NMJ inspection of the DF-RPNI muscle graft could not differentiate the motor end plates reinnervated by the divided neural sources.

