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The Effects of Muscle Graft Size to Nerve Fiber Ratio Size on Regenerative Peripheral Nerve Interface (RPNI) Reinnervation
Jennifer C Lee, MSE1; Erin Guy, BS1; Katherine L Burke, MD1; Gabriela Cinotto, MD1; Nash P Hamill, BS1; Theodore A Kung, MD2; Paul S Cederna, MD3; Stephen WP Kemp, PhD1
1University of Michigan, Ann Arbor, MI; 2Section of Plastic & Reconstructive Surgery, University of Michigan, Ann Arbor, MI; 3Plastic Surgery, University of Michigan, Ann Arbor, MI

Introduction: Currently there are more than 1.6 million people who suffer from limb loss. Regenerative Peripheral Nerve Interfaces (RPNI) currently exist as a method of capturing peripheral nerve signals for prosthetic control and preventing neuroma formation. While it is typically recommended that RPNIs are constructed to be 3 x 1 x 1.5 cm for human patients and approximately 150 mg in rat models, there is currently no recommendations or data to guide selection of muscle graft size for different nerve sizes. This consideration is especially important for RPNI construction as these factors may influence maximal optimal reinnervation for motor signal capture and neuroma . The purpose of this study was to assess the ideal ratio of nerve size to muscle graft size for maximal RPNI compound muscle action potential (CMAP) signaling.
Material and Methods: A total of 46 rats were randomly assigned to 6 experimental groups that varied the size of nerve and muscle graft for RPNI creation. Extensor digitorum longus (EDL) was harvested, and different combinations of its four muscle heads were removed to create different size muscle grafts: 20% EDL, 60% EDL, and 100%EDL. To adjust nerve size, the tibial nerve was either left untouched or divided longitudinally along the nerve for approximately 15 cm. Depending on the experimental group, either 33% or 100% of the tibial nerve was implanted into the final muscle graft. All rats underwent a 3-month maturation period before undergoing electrophysiologic testing for obtaining CMAPs. An ANOVA test with post hoc analysis was performed to test for significant differences among the groups.
Results: For 33% nerve groups, maximum average CMAPs occurred at 2.2 mV with the 60% EDL RPNI (See Figure 1). However, this average was not statistically different from that of the 20% (0.47 mV) or 100% (1.85 mV) EDL RPNI. With the 100% nerve group, maximum CMAP of the 100% EDL RPNI (4.5 mV) was significantly greater than that of the 20% (1.7 mV) or 60% (2.3 mV) EDL RPNIs. Furthermore, the maximum average CMAPs of the 100% nerve was significantly higher from that of the 33% nerve.
Conclusion: This study’s findings suggest RPNI regeneration by large nerves requires the full EDL donor muscle for maximal reinnervation in the rat model, and that full reinnervation leads to significantly larger motor signals compared to smaller nerves. Thus, muscle graft size optimization to nerve size may be necessary in the clinical setting.


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