Herbal micelles loaded oxidized dextran/gelatin hydrogel with enhanced antibacterial and microenvironment reconstruction capacity for MRSA-infected wound healing.

Bacterial resistance and complex wound microenvironment challenges the effective treatment of methicillin-resistant staphylococcus aureus (MRSA) infected wounds. Although herbal active ingredients are promising alternatives for MRSA infection therapy, their therapeutic potential is often limited by the low solubility and potential toxicity. In this study, herbal component celastrol (Cel) loaded glycyrrhetinic acid (GA) micelles were prepared based on the compatibility theory of Chinese medicine, which simultaneously increased the solubility and reduced toxicity of Cel. The prepared Cel@GA micelles were subsequently integrated into an injectable and self-healing oxidized dextran/gelatin hydrogel (DG). The obtained micelles-loaded hydrogel (DG-Cel@GA) could effectively capture surrounding MRSA and release micelles in response to the low pH in the wound site, thus significantly enhancing the antibacterial efficiency with negligible toxicity. Additionally, the hydrogel could effectively reduce pro-inflammatory factors, scavenge reactive oxygen species (ROS) and promote cell migration. In a MRSA-infected wound model in mice, the hydrogel efficiently reduced the bacterial burden, promoted angiogenesis and alleviated inflammation, and ultimately achieved high-quality wound healing. This work provides an effective solution to the challenge of administrating herbal active ingredients in the context of MRSA infected wound therapy.