**PURPOSE:** There have been many advancements in the field of neuroprosthetics for functional restoration following limb loss. However, devices that provide prosthetic users with intuitive, simultaneous motor control and somatosensory feedback have not yet been realized. Critical to the evolution of this ideal bioprosthetic device is the development of a reliable, biologic human-machine interface that facilitates transmission of both efferent motor signals for device control, and afferent somatosensory information. The Composite Regenerative Peripheral Nerve Interface (C-RPNI) is a novel biologic interface that demonstrates promise in this role. The C-RPNI is a surgical construct composed of a transected, mixed peripheral nerve implanted between a composite free graft consisting of de-epithelialized glaborous skin and skeletal muscle. The purpose of the present study was to investigate the viability and bidirectional signal transduction capabilities of the C-RPNI.

**METHODS:** C-RPNIs were surgically implanted on the end of transected common peroneal nerves of thirty F344 rats using de-epithelialized dermal grafts harvested from glaborous skin of isogenic donor rat hindpaws and free skeletal muscle grafts from the animal's contralateral limb. Thirty animals underwent endpoint testing at three months (n=15) and at six months (n=15). Electrophysiologic testing was performed to determine both the *in vivo* efferent and afferent signal transduction capabilities of C-RPNIs following electrical stimulation. C-RPNI constructs were also harvested for histologic evaluation at both three- and six-month study endpoints.

**RESULTS:** C-RPNI constructs remained viable over the study period with regeneration and revascularization evident on histologic analysis. At both three and six months, electrical stimulation of proximal peroneal nerve evoked efferent signals (CMAPs) and muscle contractions that were measured from the free muscle graft component of the C-RPNI. The average CMAP amplitude recorded from the muscle was 6.3 ± 1.4 mV at three months and 6.1 ± 1.6 mV at six months. The average conduction velocity was 11.0 ± 2.7 m/sec at three months and 12.0 ± 2.0m/sec at six months. Electrical stimulation of the dermal side of the C-RPNI evoked afferent signals (CSNAPs) in the proximal peroneal nerve at both three and sixth months. The average peak-to-peak CSNAP amplitude was 391.6 ± 145.0 µV at three months and 267.1 ± 143.8 µV at six months. The average conduction velocity with an average conduction velocity was 11.6 ± 3.0 m/sec at three months and 9.6 ± 2.4 m/sec at six months.

**CONCLUSIONS:** C-RPNI constructs remained viable with preserved innervation for six months following implantation. Recorded efferent motor signals and evoked afferent signals remained robust over time. The C-RPNI facilitates bidirectional signal transduction of both efferent motor signals and afferent sensory signals. This confirmation of bidirectional signal transduction in the C-RPNI validates the potential role of the C-RPNI in human-machine interfacing.
