Multifunctional sericin/alginate hydrogel integrated with cerium oxide nanozyme for accelerating methicillin-resistant Staphylococcus aureus-infected wound healing

Wounds complicated by multidrug-resistant (MDR) bacterial infections have posed a severe clinical challenge. The development of innovative and efficient antibacterial materials is of great importance for the management and treatment of MDR-infected wounds. Herein, an injectable sericin/alginate-based hydrogel (CeBG) was constructed by the incorporation of antibacterial compound berberine (BBR)-containing cerium oxide nanozyme. Interestingly, hybrid CeBG exhibited better gelation behavior and mechanical stability compared with the traditional calcium alginate hydrogel. Additionally, CeBG with a highly porous architecture revealed exceptional swelling and adhesive properties. CeBG showed good injectability, biocompatibility, free radical scavenging capacity and effective antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA). In the MRSA-infected mouse model, multifunctional CeBG demonstrated the most pronounced wound healing efficacy among all treatment groups. The CeBG-treated group exhibited markedly elevated expression levels of CD31, VEGF, and α-SMA. Notably, CeBG remodeled the inflammatory microenvironment in vivo and influenced macrophage polarization through the regulation of the Toll-like receptor (TLR)/NF-κB signaling pathway, leading to a decrease in pro-inflammatory cytokines like IL-1β, TNF-α and IL-6, while enhancing the production of the anti-inflammatory cytokine IL-10, thus alleviating wound inflammation. Taken together, this composite hydrogel exhibited excellent antibacterial activity and potent antioxidant capacity, offering great potential in the treatment of MRSA-infected wounds.