Nanosheet-reinforced smart polysaccharide hydrogels for MRSA-infected wound healing

Wounds infected with methicillin-resistant Staphylococcus aureus (MRSA) face clinical challenges owing to antibiotic resistance and biofilm formation. To overcome this problem, we developed a nanosheet-reinforced smart hydrogel (QCS/OHA-DM) based on the dynamic Schiff base bonds between quaternized chitosan (QCS) and oxidized hyaluronic acid (OHA) doped with polydopamine (PDA)-coated molybdenum disulfide (MoS₂) nanosheets. The hydrogel showed excellent injectability, self-healing properties, and adhesion strength (37.34 kPa at a MoS₂@PDA concentration of 3 mg/mL). Besides, owing to the introduction of the photothermal (PTM) MoS₂@PDA nanosheet, the hydrogel demonstrated excellent PTM conversion efficiency (40.9%), an ability to clear up to 85.4% reactive oxygen species within 5 min, and antibacterial properties with a bactericidal rate exceeding 95% against S. aureus, Escherichia coli, and MRSA. Cell experiments verified both the non-toxic nature of QCS/OHA-DM and its capacity to promote cell migration. QCS/OHA-DM accelerated MRSA-infected mouse wound healing and complete closure was achieved by day 12 under exposure to 808-nm near-infrared (NIR) light. Furthermore, pathological analysis indicated that after day 7 post-treatment, there were few inflammatory cells within the QCS/OHA-DM3 + NIR group along with a 125.3-μm epidermal thickness and 352.8% collagen area ratio. In addition, immunofluorescence studies illustrated that this nanosheet-reinforced, functional polysaccharide hydrogel could effectively modulate inflammatory responses while stimulating cell proliferation and angiogenesis, thereby facilitating tissue repair.