57. Functional Reinnervation of Cutaneous Mechanoreceptors in a Biologic Patient-prosthetic Peripheral Nerve Interface for the Restoration of Sensory Feedback
Year: 2023
Type: article
Abstract: PURPOSE: Sensation is critical for interacting with the environment, modulating movement, and determining one’s limb position. Current prosthetic-user interfaces cannot facilitate meaningful and intuitive sensory feedback due to instability, modality mismatch, and somatotopic mismatch. These limitations lead to unnatural or painful sensations, failure of prosthetic embodiment, and prosthetic abandonment. Our lab has developed the Dermal Sensory Regenerative Peripheral Nerve Interface (DS-RPNI) as a novel biologic sensory interface. The construct is composed of deepithelialized dermal grafts wrapped around transected sensory nerves. We have previously shown that stimulation of DS-RPNI with mechanical and electrical stimuli can elicit sensory nerve action potentials (SNAP). We hypothesize that this response is facilitated by physiologic reinnervation of mechanoreceptors in the dermal grafts by transected peripheral afferents. METHODS: Adult male Lewis rats (n=18) underwent sural nerve transection and implantation of the proximal nerve end into acellular dermal matrix (ADM, which lacks sensory targets for reinnervation) or de-epithelialized dermal graft from a donor hindpaw (DS-RPNI). After a 3-month maturation period, the constructs were harvested for immunofluorescence. Basic morphology of cutaneous mechanoreceptors was assessed with reactivity to S100 protein and vimentin, and reinnervation with reactivity to neurofilament (NF200). RESULTS: At postoperative month three, DS-RPNI showed reinnervation of mechanoreceptors, which was not seen in the ADM group. These mechanoreceptors included Ruffini, Meissner-like, and Pacinian corpuscles. Reinnervated Ruffini corpuscles displayed axonal branching within its spindle-shaped structure, whereas reinnervated Meissnerlike corpuscles were ellipsoid with nerve fibers encircling it in spiral coils. Reinnervated Pacinian corpuscles were onion-shaped with a central axon. Importantly, the morphology of the corpuscles was preserved despite prior denervation during graft harvest and appear similar to corpuscles in normal skin. CONCLUSION: Reinnervation of cutaneous mechanoreceptors and maintenance of the corpuscle morphology in DS-RPNI suggest that SNAP generation after DS-RPNI stimulation is facilitated by functional reinnervation. The results of this study demonstrate the potential of the DS-RPNI as a novel biologic sensory patient-prosthetic interface that can facilitate multimodal tactile sensory feedback. Reinnervation of mechanoreceptors in DS-RPNI at postoperative month three. (A) Ruffini corpuscles; (B) Meissner-like corpuscles; (C) Pacinian corpuscles. VIM=vimentin, NF200=neurofilament.
Institution: University of Michigan
Language: English
Subfield: Cellular and Molecular Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,195
OpenAlex ID: W4377047540