In this study, an ideal nano-scale material, named epidermal stimulating (ES) factors-gelatin/polycaprolactone (GT/PCL) nanofiber, was fabricated using a coaxial electrospinning technique. The ES-GT/PCL nanofibers possessed a highly porous structure with qualified mechanical properties for transplantation. With ES factors stored in the core and GT/PCL in the shell, the ES factors could be protected and released in a sustained manner. After seeding L929 cell line on ES-GT/PCL nanofibers for 7 daysin vitro, the proliferation of cells was nearly 1.5 folds compared to the control group. Thein vivostudy showed that ES-GT/PCL nanofibers can accelerate skin wound healing rate during the healing course, especially on the early stage. The epidermal and dermal thickness, as well as skin appendages and fat tissue, were the most similar to the native skin. These findings provided valuable insights into the addition of multiple bioactive factors to nanometre biomaterials, and optimising the advantages of the compositions as a promising potential dermal substitute construct.