Tension-Based Strategies for End-to-End Repair of Moderate and Large Nerve Gaps
Elisabeth Orozco, M.S.1, Jae Jun Nam, M.D.2, Koichi Masuda, MD1, Justin M. Brown, MD3 and Sameer B. Shah, PhD1, 1University of California, San Diego, La Jolla, CA, 2Korea University Anam Hospital, Seoul, Korea, Republic of (South), 3Massachusetts General Hospital, Boston, MA
Introduction: Current strategies for repairing severe peripheral nerve injuries are often unsuccessful, leaving patients with motor dysfunction, sensory loss, and chronic pain. End-to-end repairs yield superior functional recovery compared to graft-based repair. However, such repairs require nerve ends to be in close proximity to avoid excessive tension at the repair site. Thus, for larger gaps, autografts remain the gold-standard. We developed graft-free, implantable 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.
Materials and Methods: In one set of experiments, moderate 10-15mm nerve gaps were reconnected end-to-end following redistribution of tension away from the repair site. To this end, proximal and distal stumps were safely secured in custom-designed nerve cuffs and guided together along a rigid backbone prior to performing an end-to-end repair. In the second set of experiments, a large 25-30mm nerve gap was repaired. Nerve stumps were secured to nerve cuffs as above. The proximal stump was progressively drawn towards the distal stump gradually by means of an externalized guidewire, which moved the proximal cuff aalong a rigid backbone. After daily lengthening for 2 weeks, nerves stumps were trimmed and sutured together end-to-end, tension-free. Structural regeneration was evaluated through neuro-muscular immuno-histochemistry. Proximal nerve stumps were labeled with nodal markers, beta3-tubulin, and laminin to evaluate the morphology of lengthened neurons. Distal stump cross sections were labeled with beta3-tubulin and laminin to obtain axonal count/density. Endplate density and morphology were assessed using alpha-bungarotoxin labeling and muscle fiber size was calculated based on laminin labeling. Tibialis anterior twitch and tetanic forces and rabbit paw spread were evaluated as functional outcomes.
Results: 6 months after injury, regenerative structural and functional outcomes were significantly enhanced in tension redistributed end-to-end repairs (Study 1) and in gradually lengthened end-to-end repaired nerves (Study 2) compared to corresponding autograft repairs. Among key improvements were increased nerve cross-sectional area, axonal and nodal density and organization, muscle fiber area, and neuromuscular junction density. Twitch and tetanic stresses were also significantly higher in tension-based strategies versus autografts.
Conclusion: For moderate gaps, redistributing tension away from the repair site into healthy nerve regions allows for superior functional outcomes compared to autografts. Progressive nerve lengthening followed by end-to-end repair enhances regenerative outcomes for large nerve gaps compared to gold-standard autografts. Tension-based strategies offer a promising alternative to graft-based approaches.
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