Scaffolds that mimic the nanofibrous structures of extracellular matrix (ECM) are essential for cell adhesion and proliferation in tissue engineering. In this study, silk fibroin (SF) scaffolds with interconnected porous and ECM-like nanofibrous structures were prepared by successfully combining supercritical CO2 technology with a porogen leaching process. The effects of pressure and concentration of the SF solution on the nanofibrous structures of the SF scaffolds were not significant. By manipulating the proportion of porogen, SF scaffolds with a porosity of (32.7 +/- 1.7) % to (82.1 +/- 2.3) % and a mechanical strength of (237.0 +/- 2.2) kPa to (163.0 +/- 6.5) kPa were fabricated. In vitro biocompatibility evaluation using a MIT assay, DAPI staining, and SEM observation indicated that the SF scaffolds exhibited no toxicity and could facilitate Schwann cell attachment and proliferation. Therefore, the biomimetic SF porous scaffolds with ECM-like nanofibrous structure have potential application in nerve regeneration. (C) 2019 Elsevier B.V. All rights reserved.