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Improving Outcome Following Large Deficit Peripheral Nerve Injury: The Application of Photochemical Tissue Bonding and Crosslinked Amnion Nerve Wraps
Neil G. Fairbairn, MD1; Joanna Glazier1; Amanda Meppelink1; Mark Randolph1; Ian Valerio, MD, MS, MBA2; Mark Fleming, DO3; Robert Redmond4 ; Jonathan Winograd1
1Plastic and Reconstructive Surgery, Massachusetts General Hospital, Boston, MA; 2Division of Plastic and Reconstructive Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA; 3Department of Orthopaedics and Rehabilitation, Walter Reed National Military Medical Center, Bethesda, MD; 4Wellman Centre for Photomedicine, Massachusetts General Hospital, Boston, MA
Introduction: Photochemical tissue bonding (PTB) uses visible light to create sutureless, non-thermal, watertight bonds between two closely apposed tissue surfaces stained with a photoactive dye. When used with a human amnion nerve wrap for end-to end nerve repair, this technique results in superior functional and histological outcomes in comparison to conventional epineurial suture. When applied to large gap injury and nerve grafting, this technique has been limited by proteolytic degradation of amnion and photochemical bonds during extended periods of recovery. Chemical crosslinking of nerve wraps prior to PTB may improve wrap durability and efficacy of technique. By investigating several candidate nerve wraps and fixation techniques, we have attempted to ascertain the optimal approach for these challenging injuries.
Methods: Three candidate nerve wraps (human amnion (HAM), crosslinked human amnion (xHAM), crosslinked swine intestinal sub-mucosa (xSIS)) and 3 fixation methods (suture, fibrin glue, PTB) were investigated. Crosslinking was performed using (1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC)/N-hydroxysuccinimide (NHS). Biomechanical tests were performed using a tensiometer. Wrap durability was assessed using collagenase degradation assay. 110 inbred male Lewis rats had 15mm left sciatic nerve defects created and repaired with reversed isografts. 9 groups (n=10) had isografts secured by one of the aforementioned wrap/fixation combinations. Positive and negative control groups (n=10) were repaired with graft+suture and no repair respectively. Outcomes were assessed using monthly sciatic function index (SFI), and following sacrifice after 5-months, gastrocnemius muscle mass retention and nerve histomorphometry. Statistical analysis was performed using ANOVA and the post hoc Bonferroni test. Significance was set at p<0.05.
Results: Optimal tensile strength, photochemical bond strength and resistance to collagenase degradation were achieved using 4mM EDC/1mM NHS. Following sacrifice, crosslinked nerve wraps were still present. Un-crosslinked material was completely degraded. Nerves repaired using xHAM+PTB experienced greatest recovery of SFI although this was not statistically significant compared with standard repair (-67.9+/-5.1 vs -71.7+/-4.8). xHAM+PTB repairs also recovered greatest muscle mass retention and this was statistically significant in comparison to standard repair (67.3% +/- 4.4 vs 60.0% +/- 5.2). No significant difference in axon diameter existed between treatment groups. Fiber and axon diameter and myelin thickness were all significantly greater in the xHAM+PTB group in comparison to standard repair (6.87?m+/-2.23 vs. 5.47?m+/-1.70; 4.51?m+/-1.83 vs. 3.50?m+/-1.44; 2.35?m+/-0.64 vs. 1.96?m+/-0.47, respectively).
Conclusions: Crosslinking of nerve wraps improves tensile strength, resistance to biodegradation and preserves photochemical bonding. xHAM+PTB creates water-tight, sutureless bonds and results in superior muscle retention and histomorphometry in comparison to conventional suture repair.
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