Bacterial biosurfactant-reinforced chitooligosaccharide/polyvinyl alcohol hydrogels accelerate methicillin-resistant Staphylococcus aureus-infected wound healing by attenuating its virulence factors.

Methicillin-resistant Staphylococcus aureus (MRSA) causes widespread infections and poses serious public health concerns. Its high level of resistance to multiple antibiotics has garnered growing interest in identifying and applying novel antibacterial compounds derived from natural sources. In this study, we purified a biosurfactant (BS) from Bacillus rugosus HH2 to develop a natural antibacterial agent. This agent was then reinforced with chitooligosaccharide (COS) and polyvinyl alcohol (PVA) to create a hydrogel that promoted healing in MRSA-infected wounds. The COS/PVA/BS hydrogel was readily fabricated via the freeze-thaw method and demonstrated excellent mechanical strength, biological activity, and biocompatibility. In vitro assays confirmed that the hydrogel significantly enhanced the proliferation, migration, angiogenesis, and extracellular matrix deposition of fibroblasts, keratinocytes, and endothelial cells. Moreover, it exhibited strong bacteriostatic and bactericidal activities against MRSA, along with potent antibiofilm activity and inhibition of virulence factors relevant to MRSA-induced wound infections. Its anti-virulence effects have been linked to the downregulation of quorum sensing and virulence-related genes in MRSA. In an in vivo model of MRSA-induced infection, the COS/PVA/BS hydrogel significantly accelerated wound healing and markedly reduced the MRSA burden. Immunofluorescence staining confirmed enhanced neovascularization and regulated macrophage responses, underscoring the angiogenic and immunomodulatory effects of the hydrogel. Overall, the COS/PVA/BS hydrogel represents a promising therapeutic strategy for addressing antibiotic-resistant bacterial infections and promoting wound repair, supported by the use of common raw materials, a simple fabrication process, and high-yield production of natural antibacterial agents.