Purpose: The combination of decellularized nerve allograft and adipose-derived stromal cell -ASCs- represents a good alternative to nerve autograft for bridging peripheral nerve defects by providing physical guiding and biological cues. However, regeneration outcome of acellular nerve allograft -ANA- is often inferior to autograft. Therefore, we hypothesized that ALCAR treatment and implantation of ASCs embedded ANA would work synergistically to promote nerve regeneration. Methods: Seventy rats were randomly allocated into seven experimental groups -n = 10- including the healthy control group, sham surgery group, autograft group, ANA group, ANA + ASCs group, ANA + ALCAR group -50 mg/kg for two weeks- and ANA + ASCs + ALCAR -50 mg/kg for two weeks- group. All grafts were implanted to bridge long-gap -10 mm- sciatic nerve defects. Functional, electrophysiological and morphological analysis was conducted during the experimental period. Results: We found that the ALCAR potentiated the transplanted survival and retention of ASCs and upregulates the expression of neurotrophic factors mRNA in transplanted graft. Sixteen weeks following implantation in the rat, the ANA supplemented by ASCs is capable of supporting the re-innervation across a 10 mm sciatic nerve gap, with results close to that of the autografts in terms of functional, electrophysiological and histological assessments. Conclusions: Results demonstrated that ALCAR treatment improved regenerative effects of ANA combined with ASCs on reconstruction 10 mm sciatic nerve defects in rats as comparable to those of autograft.

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