Integrin-binding pro-survival peptide engineered silk fibroin nanosheets for diabetic wound healing and skin regeneration

Diabetics face multiple long-term health complications and diabetic foot ulcers affect approximately 15–20% of the diabetic population. The high disability rate of these patients results in substantial mental burden and economic pressure to the individuals as well as the societies. Here, we report a therapeutic integrin-binding pro-survival peptide-engineered silk fibroin nanosheet that can regulate angiogenesis and promote diabetic ulcer healing. The nanosheet with thickness less than 100 nm is highly transparent and flexible, and it can firmly adhere to the biological tissue surfaces in underwater environment. The presence of integrin-binding pro-survival peptide in the nanosheet significantly upregulates the expression of angiogenesis genes and proteins of human umbilical vein endothelial cells (HUVECs). In the diabetic mouse model, the peptide-engineered nanosheet reveals significant acceleration of wound closure, epithelialization and granulation tissue formation. These findings suggest that this functional nanosheet could be a promising therapeutic candidate for complicated diabetic ulcer healing.