Membrane Fusion Nerve Repair to Improve Limb Transplant Function
Amr Mirdad, MBBS; Irene Aran Chang, HSDG; Veronika Malek, BSc; Burcu Akpunarli, MD; Maria Chicco, MBBS; Vanessa Guarnizo, BSc; Damon S Cooney, MD, PhD
Johns Hopkins University, Baltimore, MD
Background: In its relatively short history, upper extremity transplantation has improved the lives of civilians and servicemen with limb amputation; however, functional outcomes following this procedure are highly dependent on nerve regeneration. In previous experiments, polyethylene glycol (PEG) fusion at the time of nerve transection was recently shown to re-establish axonal continuity. We propose to test whether PEG fusion can be used to improve functional outcomes after extremity transplantation. As the first step we have tested the effectiveness of PEG fusion after a delay simulating the ischemia-reperfusion time necessary for limb transplantation.
Methods: We performed sciatic nerve cuts and repair, with or without PEG fusion, in rats. PEG fusion was applied either immediately or six hours after injury. At post-operative week 1, we performed retrograde labelling using fluorescent tracer, which we applied distal to the cut and repair site.
Results: One week after Fluorogold application, we were able to visualize cell bodies in the spine and dorsal root ganglia of rats treated with PEG fusion, performed both immediately and six hours after injury, but not in control rats.
Conclusion: In our preliminary experiments, we observed that PEG fusion restores axonal continuity after cut and repair injury both in the immediate setting and after a 6hr delay simulating transplantation. In the next series of experiments, we will verify and quantify nerve fusion using electrophysiology, histomorphometry and retrograde labeling, as well as measure functional outcomes in rat sciatic nerve cut and repair in rat limb transplantation models.
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