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Nerve Tension as a Strategy for Enabling End-to-end Repairs in Injured Rabbit Sciatic Nerves
Elisabeth Orozco, MS1; Jae Jun Nam, MD2; Sameer B. Shah, PhD3
1UCSD, La Jolla, CA; 2Korea University Anam Hospital, Seoul, Korea, Republic of (South); 3University of California, San Diego, La Jolla, CA

Introduction: Peripheral nerve injuries have severe functional consequences. Current strategies for repairing severe nerve injuries are often unsuccessful, leaving patients with motor dysfunction, sensory loss, and chronic pain. Autografts remain the gold-standard for repairing moderate to large gaps; however, when possible, end-to-end repairs yield superior outcomes versus graft-based repairs, due to improved fascicular alignment, matched geometry, reduced probability of neuroma development, and only a single regenerative interface. We have developed device-based strategies to reconnect proximal nerve stumps to distal stumps end-to-end, following nerve lengthening across moderate and large rabbit sciatic nerve gaps, to facilitate graft-free end-to-end repair.
Materials and Methods: In the first set of experiments, tension was redistributed away from the site of repair for moderate 10mm nerve gaps. To enable tension redistribution, proximal and distal stumps were safely secured in custom-designed nerve cuffs and brought together along a rigid backbone prior to performing an end-to-end repair. In the second set of experiments, a large 20-30mm nerve gap was created. Nerve stumps were secured to nerve cuffs as above. The proximal stump was progressively drawn towards the distal stump using an externalized guidewire along a rigid backbone. After daily lengthening for 2 weeks, nerves stumps were freshened and sutured together end-to-end, tension-free. Both groups were compared to reversed autograft repairs of 10mm nerve gaps. Muscle mechanics on the tibialis anterior (TA) muscle by stimulation of the peroneal nerve and toe spread analysis were performed to evaluate function. Immunohistochemistry (IHC) was performed to evaluate structural regeneration; distal stump nerve cross sections were stained with ?3-tubulin and laminin to obtain axonal counts, density, and coverage.
Results: At 24 weeks, functional outcomes were enhanced in tension redistributed end-to-end repairs (Study 1), including ~3.5-fold improvement in TA twitch tension (p<.005) and ~2-fold improvement in TA tetanic tension (p<0.03) vs. autografts. Initial results in progressively lengthened end-to-end repaired nerves (Study 2, n = 2-4 per group) also showed ~3-fold improvement in twitch tension and ~30% improvement in tetanic tension vs. autograft repairs. Improved toe-spread was also observed for lengthening/end to end repair in both studies vs. autograft. IHC showed correspondingly enhanced axonal counts, density, and coverage in both device groups vs. autografts.
Conclusion: Redistributing tension away from the repair site allows safe end-to-end repairs and provides superior functional outcomes vs. gold-standard autografts for moderate nerve gaps. Progressive nerve lengthening followed by end-to-end repair enhances regenerative outcomes vs. gold-standard autografts for large nerve gaps.


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