The Composite Regenerative Peripheral Nerve Interface (C-RPNI) Facilitates Bidirectional Sensorimotor Signaling in a Rodent Model
Widya Adidharma, M.D.1, Ritvik R Jillala, BSE1, Alex K Vaskov, PhD1, Rithvik Kodali, BS1, Sara Huang, B.S.1, Kuan L Wu, MD2, Maria V Rivera-Santana, B.S.1, Paul S Cederna, M.D.1 and Stephen WP Kemp, Ph.D.1, 1University of Michigan, Ann Arbor, MI, 2Chang-Gung Memorial Hospital Linkou Medical Center and Chang Gung University College of Medicine, Taoyuan City, Taiwan
INTRODUCTION
Modern prostheses have the potential to perform complex movements and to detect sensory stimuli, offering a promising solution for restoration of limb function after amputation. However, these benefits have not been fully realized due to lack of an adequate patient-prosthetic interface that can reliably facilitate bidirectional sensorimotor signaling. We hypothesized that the Composite Regenerative Peripheral Nerve Interface (C-RPNI), a transected nerve implanted between a dermal and muscle graft, is a biologic interface that is reinnervated and can facilitate bidirectional sensorimotor signaling needed for naturalistic prosthetic control.
MATERIAL AND METHODS
Male Lewis rats (n=7) underwent C-RPNI surgery on the proximal transected common peroneal (CP) nerve. The contralateral hindleg served as an internal control. After 3 months of construct maturation, sensory nerve action potentials (SNAPs) were recorded from CP nerve during stepwise increasing C-RPNI dermal graft stimulation with a stimulating electrode. Compound motor action potentials (CMAPs) were recorded from C-RPNI muscle graft with a recording electrode during stepwise CP nerve stimulation. The minimum stimulation magnitude required to generate a waveform was defined as the stimulation threshold. Maximum amplitudes were recorded. C-RPNI results were compared to contralateral extensor digitorum longus (EDL) and sural-innervated skin. Stimuli magnitudes between the threshold and maximum for both CMAP and SNAP was calculated for C-RPNI bidirectional simulation. Bidirectional signaling was then simulated by eliciting 100 alternate SNAPs and CMAPs with 100 ms delay between stimuli. After endpoint testing, C-RPNI were harvested for immunohistochemistry.
RESULTS
Maximum C-RPNI CMAP amplitudes were comparable to control EDL (3.7mV versus 5.2mV, p=0.39). Maximum C-RPNI SNAP amplitudes were comparable to control sural-innervated hindfoot (234.1 uV versus 62.9 uV, p=0.09). Waveforms were similar between C-RPNI and control tissue. Bidirectional signaling was successfully simulated, with 1 CMAP following every SNAP over 100 consecutive bins. CMAPs and SNAPs do not change significantly in waveform or amplitude between the 1st and 100th stimulus (CMAP 3.5mV versus 3.5mV, p=0.94; SNAP 165.3 uV versus 169.7 uV, p=0.2). Muscle histomorphometry revealed muscle graft regeneration. Immunofluorescence staining revealed reinnervation of C-RPNI muscle and dermal graft end-organ targets (Figure 1).
CONCLUSION
The C-RPNI is a biologic interface that has the potential to facilitate stable bidirectional sensorimotor signaling needed for intuitive naturalistic prosthetic control.
Figure 1. Reinnervation of C-RPNI A) neuromuscular junction and B) Meissner’s corpuscles.
Back to 2024 Abstracts