Carbopol 940-based hydrogels loading synergistic combination of quercetin and luteolin from the herb Euphorbia humifusato promote Staphylococcus aureusinfected wound healing

With the increasing prevalence of Staphylococcus aureusinfections, rapid emergence of drug resistance and the slow healing of infected wounds, developing an efficient antibiotic-free multifunctional wound dressing for inhibiting S. aureusand simultaneously facilitating wound healing have become a huge challenge. Due to their excellent biocompatibility and biodegradability, some carbopol hydrogels based on plant extracts or purified compounds have already been applied in wound healing treatment. In China, Euphorbia humifusaWilld. (EuH) has been traditionally used as a medicine and food homologous medicine for the treatment of furuncles and carbuncles mainly caused by S. aureusinfection. In an earlier study, EuH-originated flavonoids quercetin (QU) and luteolin (LU) could serve as a potential source for anti-S. aureusdrug discovery when used in synergy. However, the in vivoeffects of QU and LU on S. aureus-infected wound healing are still unknown. In this study, we found a series of Carbopol 940-based hydrogels loading QU and LU in combination could disinfect S. aureusand also could promote wound healing. In the full-thickness skin defect mouse model infected with S. aureus, the wound contraction ratio, bacterial burden, skin hyperplasia and inflammation score, as well as collagen deposition and blood vessels were then investigated. The results indicate that the optimized QL2 [QU (32 μg mL−1)–LU (8 μg mL−1)] hydrogel with biocompatibility significantly promoted S. aureus-infected wound healing through anti-infection, anti-inflammation, collagen deposition, and angiogenesis, revealing it as a promising alternative for infected wound repair.