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PSRC 60th Annual Meeting
Program and Abstracts

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Regenerative Peripheral Nerve Interfaces: Impact of Decellularized Small Intestinal Submucosa on Regeneration, Reinnervation, and Revascularization
Frances M. Walocko, MSE, Elizabeth A. Mays, BSE, Zachary P. French, HS, Cheryl A. Hassett, BS, Jana D. Moon, BS, Nicholas B. Langhals, PhD, Paul S. Cederna, MD, Melanie G. Urbanchek, PhD.
University of Michigan, Ann Arbor, MI, USA.

PURPOSE: To improve reliability of myoelectric prosthetic devices, we developed the Regenerative Peripheral Nerve Interface (RPNI) for neuroprosthetic control. In our standard model, decellularized small intestinal submucosa (SIS) secures an epimysial electrode to the RPNI. However, RPNI viability and signal transduction require muscle regeneration, reinnervation and revascularization, and SIS may affect these essential processes. We determined the effects of SIS on RPNI viability by comparing muscle fiber regeneration, reinnervation, and revascularization of freely transferred muscle wrapped in SIS to those without SIS.

Rats were assigned to Standard RPNI (n=5) or RPNI without SIS (n=5) groups. RPNIs were surgically constructed with autologous unilateral, free muscle transfer to the ipsilateral upper thigh using the extensor digitorum longus (EDL) muscle. The proximal end of the divided peroneal nerve was implanted into the muscle. The EDL muscle was then either wrapped in SIS (Standard RPNI) or not (RPNI without SIS) (Figure 1). Three months postoperatively, RPNI compound muscle action potential (CMAP), force, fatigability, and histology were assessed.

All rats survived the surgery and did not differ in age or body mass. RPNIs without SIS had 32% greater CMAP amplitude and 69% decreased rheobase (minimal current required to reach depolarization threshold), indicating better muscle reinnervation (Table 1). Although RPNIs without SIS produced similar maximal forces, they recovered 82% of maximal force after 20-minutes of fatiguing work, while Standard RPNIs only recovered 44% (Table 2). Thus, fatigue testing exposed a previously hidden limitation of the SIS RPNI wrap. The 13% greater muscle mass seen in RPNIs without SIS also indicates more regeneration, better reinnervation, and commensurately increased revascularization. Muscle cross-sections were processed and analyzed for muscle health (Figure 2). Histological analysis illustrates that muscles from the RPNI without SIS group appear healthier based on the polygonal shape and homogenous appearance of their muscle fibers. Additional RPNI testing, histology, and statistical analyses are in progress.

Following three months of recovery, neurotized RPNIs without SIS demonstrated greater signal transfer, greater muscle mass, better resistance to signal fatigue, and lower stimulation required to induce a response. These results indicate that SIS wrap around RPNIs is not necessary and may even be detrimental to RPNI function.

Defense Advanced Research Projects Agency (DARPA) MTO under the auspices of Dr. Jack Judy through the Space and Naval Warfare Systems Center, Pacific Grant/Contract No. N66001-11-C-4190

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