An on-demand antibacterial hydrogel for precise and rapid elimination of bacterial infection in a murine partial thickness scald burn wound

Burn wounds trigger prolonged inflammation, impair healing, and result in a high mortality rate. The effective management of burn patients requires a targeted approach to regulate the wound microenvironment, maintaining sterility while fostering conditions conducive to healing and functionality. Here, we developed a targeted antibacterial pH/temperature-responsive silver nanoparticle (AgNP) hydrogel triggering the release of silver ions based on changes in the burn wound microenvironment. The delivery system not only exerts a strong antibacterial effect owing to the localization and interfacial interaction of ultrasmall AgNPs against the bacterial surface and deeply embedded cells within the biofilm but also downregulates the bacterial pore-forming genes, thereby overwhelmingly deactivating bacterial responses through a multifaceted mechanism of action. We demonstrate that the application of AgNP hydrogel results in pH-dependent bacterial killing and elimination of over 95 % of pathogens while being non-toxic to mammalian cell viability and migration. Furthermore, the in vivo preclinical burn infection murine model demonstrates the eradication of S. aureus infection leading to a progressive burn repair supported by increased collagen deposition, anti-inflammatory properties, and increased burn angiogenesis. Overall, this strategy provides a targeted approach to addressing drug-resistant chronic burn infections, thereby contributing to improved management of burn injuries.