Development of a bioactive silk fibroin bilayer scaffold for wound healing and scar inhibition

In cases of deep skin defects, spontaneous tissue regeneration and excessive collagen deposition lead to hyper-plastic scars. Conventional remedial action after scar formation is limited with a high recurrence rate. In this study, we designed a new artificial skin bilayer using silk fibroin nanofibers films (SNF) as the epidermis, and silk fibroin (SF) / hyaluronic acid (HA) scaffold as the dermal layer. The regenerated SF film was used as a binder to form a functional SNF-SF-HA bilayer scaffold. The bilayer scaffold showed high porosity, hydrophilicity, and strength, and retained its shape over 30 days in PBS. In vitro, human umbilical vein endothelial cells were seeded into the bilayer scaffold and showed superior cell viability. In vivo analyses using the rabbit ear hypertrophic scar (HS) model indicated that the bilayer scaffold not only supported the reconstruction of new tissue, but also inhibited scar formation. The scaffold possibly achieved scar inhabitation by reducing wound contraction, weakening inflammatory reactions, and regulating collagen deposition and type conversion, which was partly observed through the downregulation of type I collagen, transforming growth factor-beta, and alpha-smooth muscle actin. This study describes a new strategy to expand the application of silk-based biomaterials for the treatment of hyperplastic skin scars.