Through a combination of biomaterials and stem cells, tissue engineering strategies for restoring and regenerating damaged peripheral nerves have recently been used to meet the challenges posed by nerve injury. In a previous study, we revealed a new way to induce neuronal differentiation of stem cells based on the temporally sequential use of miR-218 and Fibroblast Growth Factor 2 (FGF2) in vitro (FGF2-miR-218 induction approach). In the present study, we sought to investigate the application of this novel approach in repairing sciatic nerve damage in vivo. The results showed that compared with randomly oriented nanofibers, nanofibers in an aligned orientation more favored stem cell growth and elongation. Stem cells (neuronally differentiated adipose-derived mesenchymal stem cells (ASCs)) treated with the FGF2-miR-218 induction approach and integrated with 3D aligned orientation nanofibers structures as artificial nerve grafts were implanted into 10 mm transected rat sciatic nerves in vivo. The test results of immunohistochemical staining and motor function restoration indicated that the FGF2-miR-218 induction approach combined with the 3D nanofiber scaffolds facilitated the nerve regeneration. Thus, this approach could be an effective tissue engineering method for recovery of nerve damage. (C) 2017 Published by Elsevier Inc.