Hot spring-inspired zinc-crosslinked Mesona chinensis polysaccharide hydrogel microspheres for MRSA-infected chronic wound healing.

Drug-resistant bacterial infection and the unfavorable wound microenvironment remain major barriers to chronic wound healing. This study was initiated to address these challenges by developing hot spring effect-inspired thermo-ionic hydrogel microspheres from polysaccharides extracted from Chinese mesona (Mesona chinensis), an edible and medicinal herb, and Zn2+ for the treatment of MRSA-infected chronic wounds. Leveraging endogenous polyphenols in Mesona chinensis polysaccharide (MCP) for photothermal conversion, this system avoids the safety concerns associated with conventional noble-metal photothermal materials. Under near-infrared irradiation, MCP-Ms generated local heat and promoted Zn2+ release, demonstrating potent antibacterial activity against both S. aureus and MRSA. The combined photothermal and Zn2+-related effects also promoted fibroblast and endothelial cell proliferation and migration. In vivo studies in rat and Bama pig wound infection models further confirmed that the treatment accelerated healing by reducing inflammation, enhancing collagen deposition, and stimulating angiogenesis. Transcriptomic analysis suggested the involvement of key pro-healing pathways, including PI3K-Akt and extracellular matrix-related signaling, indicating that MCP-Ms represent a promising bioinspired therapeutic strategy for drug-resistant wound infection.