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Nerve Regeneration in a Rodent Model of Segmental Nerve Deficit Injury as a Function of Nerve Wrap and Fixation Procedure
Neil G. Fairbairn, MD1, Joanna Ng-Glazier, MD1, Amanda Meppelink1, Mark A. Randolph, MAS1, Jonathan M. Winograd, MD1, Robert W. Redmond, PhD2, IL Valerio3 and Mark Fleming, DO4
1 Plastic and Reconstructive Surgery, Massachusetts General Hospital, Boston, MA, 2Wellman Centre for Photomedicine, Massachusetts General Hospital, Boston, MA, 3Plastic and Reconstructive Surgery, National Naval Medical Center, Bethesda, MD, 4Department of Orthopaedics and Rehabilitation, Walter Reed National Military Medical Center, Bethesda, MD
INTRODUCTION: Photochemical tissue bonding (PTB) uses visible light to create sutureless, non-thermal, watertight bonds between tissue surfaces stained with a photoactive dye. In recent years our group has used this technology with a biological nerve wrap to seal the regenerative milieu of end-to-end neurorrhaphy sites, showing superior outcomes in comparison to conventional repair. Proteolytic degradation of biological wraps during extended recovery periods may limit the efficacy of this technique when applied to large nerve deficits requiring reconstruction with long nerve grafts. By investigating different combinations of wrap and fixation technique and by chemically cross-linking candidate wraps to improve resistance to biodegradation, we aim to assess the efficacy of PTB for securing large nerve grafts and to ascertain the optimum wrap/fixation method of repair. METHODS: Three candidate nerve wraps (human amnion, crosslinked human amnion, crosslinked swine intestinal sub-mucosa (SIS)) and 3 fixation methods (epineurial suture, fibrin glue, photochemical tissue bonding (PTB)) were investigated. Crosslinking was performed using (1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC)/H-hydroxysuccinimide (NHS). Resistance to biodegradation was measured by digesting nerve wraps in 0.1% collagenase and performing fluorescamine degradation assays. Mechanical properties of each repair technique were measured by ex-vivo tensiometer testing. 110 inbred male Lewis rats had 1.5cm left sciatic nerve defects created and repaired with exchanged isografts. 9 groups (n=10) had isografts secured by one of the aforementioned wrap/fixation combinations. 2 groups (n=10) were used as positive (epineurial suture only) and negative (no repair) controls. Following surgery, walking track analysis was performed at monthly intervals and sciatic function index (SFI) calculated. Following sacrifice after 150-days, repaired nerves were excised for histomorphometric analysis. Left gastrocnemius muscle mass was compared to contralateral controls. RESULTS: Chemical crosslinking of candidate nerve wraps with 4mM EDC/1mM NHS resulted in optimal bond strength and resistance to collagenase degradation. High concentrations of crosslinking solution were found to impair PTB. Analysis of SFI at the 3-month time point has shown superior results in those nerves repaired using crosslinked amnion and PTB. After all animals have been sacrificed, completed functional data will be correlated to muscle weight and nerve histomorphometry. CONCLUSIONS: Whilst preserving the bonding ability of PTB, chemical crosslinking of nerve wraps improves their resistance to biodegradation. At early time points, the use of crosslinked amnion and PTB to create a water-tight, sutureless bond at nerve graft coaptation sites has produced superior functional outcomes following large deficit injury. Final outcome data will be available in the near future.
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