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Impact of Decellularized Small Intestinal Submucosa on Regeneration, Reinnervation, and Revascularization of Freely Transferred Muscle in the Regenerative Peripheral Nerve Interface
Frances M. Walocko, MS, Yaxi Hu, BS, Elizabeth A. Mays, BSE, Cheryl A. Hassett, BS, Jana D. Moon, BS, Ian C. Sando, MD, Nicholas B. Langhals, PhD, Paul S. Cederna, MD, Melanie G. Urbanchek, PhD.
University of Michigan, Ann Arbor, MI, USA.

PURPOSE: The Regenerative Peripheral Nerve Interface (RPNI) is an interface for high-fidelity control of neuroprosthetic devices. Standard RPNIs have a free muscle graft wrapped in decellularized small intestinal submucosa (SIS). However, SIS may interfere with processes of regeneration, reinnervation and revascularization of the muscle graft. The purpose of this study is to determine the impact of SIS on RPNI signaling capacity.
METHODS: Rats were randomized into 2 groups. RPNIs were constructed by a free extensor digitorum longus muscle graft wrapped in SIS (standard RPNI group, n=6) or not wrapped in SIS (RPNI without SIS, n=6). All RPNIs were neurotized by the transected peroneal nerve. Endpoint testing at 3 months post-surgery included compound muscle action potential (CMAP), force and fatigability and histology analysis.
RESULTS: At endpoints, RPNIs without SIS had an 8.9% greater muscle mass than standard RPNIs. RPNIs without SIS showed an increase of 42% CMAP amplitude and a 52% lower threshold stimulus (rheobase) compared to standard RPNIs, indicating increased muscle reinnervation (Table 1). Maximal tetanic forces were similar in both groups. However, fatigue testing showed that RPNIs without SIS recovered 80% of their maximal force, while standard RPNIs only recovered 50%.
CONCLUSIONS: RPNIs without SIS show better muscle reinnervation and regeneration compared to standard RPNIs wrapped in SIS. SIS wrapping might be a limiting factor in RPNI high-fidelity neuroprosthetic control.
Table 1. Summary of Evoked CMAP Data
Standard RPNIRPNI without SIS
Number of rats evaluated to date3/63/6
Body mass, mg385 ± 17397 ± 25
Rheobase, mA0.610 ± 0.195 0.290 ± 0.135
Latency, msec1.12 ± 0.14 1.23 ± 0.28
Amplitude, mV1.60 ± 0.66 2.27 ± 0.60
Velocity, m/s5.37 ± 2.90 9.17 ± 3.40
CMAP area, mV*msec2.27 ± 1.642.27 ± 0.90
CMAP duration, msec2.40 ± 1.302.15 ± 0.31
Values presented are means ± 1 standard deviation. Abbreviations: mg, milligrams; mA, milliamps; msec, milliseconds; mV, millivolts; m, meters; s, seconds.


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