Effect of Reverse End-to-Side (Supercharging) Neurotization in Long Processed Acellular Nerve Allograft in a Rat Model

Abstract

Processed acellular nerve allograft (PNA) has been suggested as a convenient tool for overcoming short and medium nerve defects. Although the clinical implications are unclear, animal data suggest that PNA becomes less effective at longer lengths. Although reverse or supercharging end-to-side nerve transfer may improve the neurotrophic potential in chronically denervated nerve tissue, the application of this strategy to long acellular nerve allograft has not been previously investigated. We hypothesized that supercharging acellular nerve allograft would increase its effective length. Sprague-Dawley and Thy1-green fluorescent protein Sprague-Dawley rats underwent transection of the tibial nerve, followed by immediate repair with 20-, 40-, or 60-mm acellular nerve allografts processed identically to commercially available human acellular nerve allograft (AxoGen, Inc., Alachua, FL) or isograft. Half of the allograft group was supercharged with a reverse end-to-side transfer from the ipsilateral peroneal nerve. At 10 weeks, the reconstructed nerve in the Thy1-green fluorescent rat groups were exposed and examined under a fluorescence-enabled microscope. At 20 weeks, the remaining rats underwent motor testing and tissue harvest for morphological examination. In comparison with a nonenhanced allograft, supercharging had a statistically significant positive impact on the reinnervated muscle normalized force generation and distal axon counts for all graft sizes. Muscles in the supercharged group were heavier than those in the allograft group for the 40-mm-length grafts and G-ratio measurements were higher in the supercharged allograft group for 60-mm-length grafts only. This study supports that hypothesis that supercharging nerve transfer improves axon regeneration within PNA. When an appropriate donor nerve is available, supercharging nerve transfer may improve nerve regeneration in PNA across long nerve defects.