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Independent Control of Sensorimotor Function using Superficial Regenerative Peripheral Nerve Interfaces (S-RPNIs) in a Rat Model
Amir Dehdashtian, MD, MPH1; Gabriela Cinotto, MD1; Erin Guy, BS1; Keith D Kozma, BSc1; Sara L Huang, BSc1; Katherine L Burke, MD1; Widya Adidharma, MD2; Paul S Cederna, MD3; Stephen WP Kemp, PhD1
1University of Michigan, Ann Arbor, MI; 2University of Michigan, Ann Arbor, WA; 3Plastic Surgery, University of Michigan, Ann Arbor, MI

Introduction: Although advanced prosthetic devices have the potential to allow fine-motor movements and extract somatosensory signals, an ideal human-machine interface currently doesnít exist. The Regenerative Peripheral Nerve Interface (RPNI) was developed as a stable biologic interface through implantation of a residual nerve into an autogenous free muscle graft. However, current RPNI approaches depend on indwelling electrodes for either motor control or sensory feedback. The current study investigated the placement of RPNIs directly underneath defatted skin in rats to capture motor control signals using surface electrodes, while simultaneously creating a sensory interface by reinnervation of the overlying skin.
Methods: 24 male Lewis rats underwent baseline pain assessment by tapping a 26g filament over the lateral thigh and recording the ratio of pain response (similar to Tinelís test). Next, all rats were randomly assigned to the following groups (n=6/group): G1- sham surgery; G2- Tibial neuroma; G3- Tibial RPNI; G4- Tibial and common peroneal (CP) RPNIs (double RPNI). For G2-G4, tibial or CP nerves were transected distally in the thigh and moved directly under the skin. For the neuroma group, the transected tibial nerve was sutured to the dermis and the skin was marked on top to serve as a target for weekly pain assessments. For RPNI groups, transected nerves were implanted into autologous EDL muscles grafts. Skin overlying the RPNIs was defatted and marked for the pain assessment (figure A-C). Following 12 weeks, endpoint electrophysiologic testing using surface electrodes was performed and measured compound muscle action potentials (CMAPs) and compound sensory nerve action potentials (CSNAPs). Additionally, for G2 and G3, minimum von Frey filament threshold to generate CSNAP was recorded. Finally, en-bloc skin and RPNIs were harvested for whole-mount immunostaining.
Results: The neuroma group showed significantly higher pain responses when compared to all other groups. Pain responses in all RPNI and sham groups were not statistically different from one another. The neuroma group displayed lower thresholds to generate CSNAPs than RPNIs when mechanically stimulated. Stimulation of proximal nerve resulted in robust and independent recording of CMAP readily accessible through the skin. Moreover, electrical stimulation of the skin generated independent CSNAPs in the corresponding proximal nerve (figure D-G)
Conclusion: S-RPNI is a viable and simple surgical strategy that has the potential to transmit simultaneous, real-time, and independent sensory and motor signals between a residual nerve and a prostheses.


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