In situ photo-crosslinking silk fibroin based hydrogel accelerates diabetic wound healing through antibacterial and antioxidant

Bacterial infection and excessive reactive oxygen species (ROS) in diabetic wounds lead to a prolonged inflammatory phase, and injuries are highly susceptible to developing into chronic wounds. Improving the poor microenvironment is vital to achieving effective diabetic wound healing. In this work, methacrylated silk fibroin (SFMA) was combined with ε-polylysine (EPL) and manganese dioxide nanoparticles (BMNPs) to form an SF@(EPL-BM) hydrogel with in situ forming, antibacterial and antioxidant properties. EPL imparted high antibacterial activity (>96 %) to the hydrogel. BMNPs and EPL showed good scavenging activity against a variety of free radicals. SF@(EPL-BM) hydrogel had low cytotoxicity and could alleviate H2O2-induced oxidative stress in L929 cells. In diabetic wounds infected with Staphylococcus aureus (S. aureus), the SF@(EPL-BM) hydrogel exhibited better antibacterial properties and reduced wound ROS levels more significantly than that of the control in vivo. In this process, the pro-inflammatory factor TNF-α was down-regulated, and the vascularization marker CD31 was up-regulated. H&E and Masson staining showed a rapid transition from the inflammatory to the proliferative phase of the wounds, with significant new tissue and collagen deposition. These results confirm that this multifunctional hydrogel dressing holds well potential for chronic wound healing.