Efficacy Of Amniotic Membrane Nerve Wraps In A Rat Sciatic Nerve Reverse Autograft Model
Erin M. Wolfe, BS, Sydney A. Mathis, BS, Natalia de la Oliva Munoz, PhD, Daisy I. Gonzalez, BS, Steven A. Ovadia, MD, Prakash J. Mathew, MD, Damien D. Pearse, PhD, Martin Oudega, PhD, Zubin J. Panthaki.
University of Miami Miller School of Medicine, Miami, FL, USA.
PURPOSE: Nerve wraps provide a protective encasement around peripheral nerves following neurorrhaphy. Various types of nerve wraps are available for use in clinical practice. Human amniotic membrane (hAM) is an easily obtainable FDA-approved biomaterial with no donor site morbidity and minimal inflammatory response. hAM nerve wraps provide a neurotrophic effect, containing human mesenchymal stem cells (hMSC) and human amniotic epithelial cells (hAEC) which have multilineage differentiation potential and can synthesize and secrete neurotrophic factors, differentiate into neural phenotypes and enhance Schwann cell proliferation. The purpose of this study was to evaluate the efficacy of hAM nerve wraps in a rat sciatic nerve reverse autograft model. METHODS: Lewis rats underwent sciatic nerve injury and repair in which a 10-mm gap was bridged with a reverse autograft combined with either no nerve wrap (control) or hAM nerve wrap. Functional evaluation including the Sciatic Functional Index (SFI) and CatWalk gait analysis was performed at baseline, 4, 8 and 12 weeks. Electrophysiological studies were conducted at 8, 10 and 12 weeks. Gastrocnemius muscle weight ratios and nerve adhesions were evaluated at 12 weeks. Axonal regeneration, perineural fibrosis and muscle atrophy were investigated via histological evaluation and retrograde labeling at 12 weeks. RESULTS: Immunohistochemical analysis demonstrated that hAM-treated animals had significantly higher numbers of axons compared to controls. hAM-treated nerves had significantly less perineural fibrosis and nerve adhesions compared to controls. Analysis of SFI demonstrated significant improvements in the hAM-treated group compared to control groups, and CatWalk analysis demonstrated that hAM treated animals had a higher average mean stand time on the injured limb a well as an improved mean swing time at 8 and 12 weeks; however, these differences were not significant. The ratio of experimental to control gastrocnemius weights was significantly greater in hAM compared to control groups. The normalized CMAP of hAM animals was significantly improved compared to controls at 10 weeks. Retrograde labeling demonstrated that significantly greater numbers of motoneurons were regenerating axons in the hAM group compared to controls. CONCLUSION: Functional, electrophysiological and histological evaluation demonstrated that hAM nerve wraps improved outcomes compared to controls. Anti-inﬂammatory and pro-regenerative eﬀects of hAM may result in reduced scarring and improved axonal regeneration and functional recovery, make it a promising biomaterial for clinical applications in peripheral nerve repair.
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