American Society for Peripheral Nerve

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Functional and Histological Evaluation of a Novel Branched Acellular Nerve Allograft and Processed Human Xenograft with and without FK506 in a Complex Branching Facial Nerve Defect: A Preliminary Study in Swine
Mario A. Aycart, MD; Muayyad Alhefzi, MD; Ericka M Bueno, PhD; Bohdan Pomahac, MD
Brigham and Women's Hospital, Boston, MA

Introduction: The gold standard for peripheral nerve gap repair remains the autologous nerve graft. However, "off-the-shelf" alternatives are appealing due to additional graft material, shorter operative times and avoidance of donor site morbidity. Such commercially available products may hold particular interest in large gap, complex branching nerve defects. This study aims to evaluate the functional and histological regeneration of a novel branched acellular nerve allograft (ANA) and processed human xenograft with and without oral FK506 in a 30mm complex branching facial nerve defect in a large animal model.

Methods: Yucatan miniature swine (n = 10) underwent transection of the inferior division of the facial nerve at a point 5mm proximal to the branching point of the marginal mandibular and cervical nerve branches and 25mm distal to the transection to create a 30mm nerve gap. The gap was addressed either by a species-specific ANA (n=4), a processed human xenograft with FK506 (n=4) or a processed human xenograft without FK506 (n=2). FK506 was given as a twice daily oral administration and continued for the entire duration of study. Goal whole blood trough levels were set to 4-8 ng/mL in order to evaluate the role of low-dose FK506 while minimizing the side effects of chronic FK506 and drug-related toxicity. Electrophysiologic assessments were performed at study end point (24 weeks) to assess functional recovery. Distal nerve stumps were harvested for immunohistochemical evaluation using neurofilament and S100 to observe the distribution and presence of Schwann cells in the respective nerve fibers.

Results: After 24 weeks, processed human xenografts treated with FK506 demonstrated a non-statistically significant (p=0.16) improvement across functional parameters, as measured by electrophysiologic studies (mean marginal mandibular nerve amplitude 3.82 0.69 mV) against species-specific ANA (mean marginal mandibular nerve amplitude 2.96 0.32 mV) and processed human xenografts without FK506 (mean marginal mandibular nerve amplitude 2.94 0.95 mV). Mean FK506 trough levels were 5.76 4.9 ng/mL with no mortalities. Nerves repaired with a xenograft and FK506 had greater appreciable costaining of neurofilament and S100 distal to the repair site compared to other groups.

Conclusion: In this study, we demonstrate the use of a novel branched ANA and processed human xenograft with and without oral FK506 in a complex branching facial nerve defect in a large animal model. Low-dose FK506 appears to enhance and support a processed human xenograft across a large gap, branched nerve defect. Ongoing efforts are being directed towards isograft and histomorphometric outcomes.

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