Tissue-engineered skin substitutes such as nanofibers from traditional electrospinning may offer an effective therapeutic option for the treatment of patients suffering from skin damages such as burns and diabetic ulcers. However, it is generally difficult for cells to infiltrate the nanofibers due to their small pore size and sheets-like appearance. In the present study, a facile and efficient strategy has successfully been introduced that can produce 3D silk fibroin nanofibers, obviating an intrinsic limitation of traditional and salt-leaching electrospinning by introducing cold-plate electrospinning. The cell attachment and infiltration studies indicated the use of 3D nanofiber scaffolds by cold-plate electrospinning as a potential candidate to overcome intrinsic barriers of electrospinning techniques. The 3D nanofiber scaffolds using this technique presented a high porosity with controlled thickness and an easy contouring of facial shape; these properties can contribute to the ideal candidate for artificial skin reconstruction. (C) 2015 Elsevier Inc. All rights reserved.