Plastic Surgery Research Council

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Large Gap Peripheral Nerve Repair in a Non-Human Primate Model: Improving Outcomes Utilizing Photochemical Tissue Bonding (PTB) with Acellular Nerve Allograft (ANA)
Marek A. Hansdorfer, M.D.1, Jane M. Tsui, M.D.1, Marco Visaggio, M.D.1, Gem G. Runyan, M.S.1, Mark A. Randolph, M.A.S1, William S. David, M.D., Ph.D.2, Reiner B. See, M.D.2, Ian L. Valerio, M.D., M.S., M.B.A.3, Jonathan M. Winograd, M.D.1, Robert W. Redmond, Ph.D.4.
1Division of Plastic and Reconstructive Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA, 2Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA, 3Department of Plastic and Reconstructive Surgery, The Ohio State University Wexner Medical Center, Columbus, OH, USA, 4Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.

PURPOSE:
Segmental peripheral nerve deficits are challenging injuries associated with poor outcomes. While these injuries afflict civilians (e.g. Boston Marathon Bombing), they have become increasingly prevalent in combat trauma since the advent of improvised explosive devices. Standard of care large-gap (>3cm) reconstruction requires nerve autograft. Alternatives are sought in clinical scenarios where donor limb is not available (e.g. multiple extremity trauma) or donor site morbidity (e.g. painful neuroma formation, loss of function) makes autograft use suboptimal. A variety of alternatives have been proposed including allografts and conduits. Photochemical tissue bonding (PTB) as an alternative to traditional suture neurorrhaphy has been extensively studied in the rodent sciatic nerve model. PTB carries several advantages: reduction of needle trauma, prevention of axonal escape, and a water-tight seal to contain neuroregenerative factors and exclude inflammatory invasion. We report a non-human primate study which recapitulates human anatomy, allows for objective quantitative functional outcomes testing, electrophysiology and histomorphometry. The purpose of this study is to evaluate whether PTB can elevate the performance of acellular nerve allograft (ANA) to that of standard of care autograft/suture.
METHODS:
Nineteen rhesus macaques underwent 4cm proximal radial nerve defect creation in the right upper extremity, the radial nerve transected proximally at the humeral spiral groove, distally prior to the branch to brachioradialis. The radial nerve was selected as it is responsible for an isolated function with no input from other nerves. Three repair techniques were evaluated: n=6 autograft/suture, n=6 ANA/suture, n=7 ANA photosealed in place with light-activated human amnion wraps (PTB). An objective functional outcome test was conceived using an apparatus that accurately measured the degree of wrist extension as a function of time after surgery [Figure 1A]. Electromyography (EMG) was performed at 0, 120, 240, and 365 days (euthanasia). Histomorphometry and muscle mass retention were analyzed at euthanasia.
RESULTS:
Average loss of wrist extension was 88.38.2 after radial nerve defect creation [Figure 1B-C]. Autograft group animals recovered 82.0 of extension by 7 months [Figure 1D,F]. Wrist extension recovery was modestly slower, as expected, in the ANA groups, however, by 8 months the ANA/PTB group recovered 63.0 of extension [Figure 1 E-F] with no difference in recovery of baseline EMG amplitude as compared to controls (Avance/PTB=75.81% vs. autograft/suture=65.06%). If recovery follows current trajectory, we expect ANA/PTB to demonstrate equivalent outcomes to the autograft/suture group at one year.
CONCLUSION:
This radial nerve defect model improves upon existing animal models by allowing for large nerve gap testing in a primate model more analogous to the clinical large nerve gap injury in humans. ANA/PTB group functional recovery lagged modestly behind autograft/suture (by as long as 8 weeks) but is approaching equivalence at 8 months. EMG recovery is similar at 8 months. This preliminary data confirms PTB as a promising technique to improve outcomes of large nerve gap reconstruction in combination with autograft (previously demonstrated) and with acellular nerve allograft.


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