Infection-adaptive reversible switch to On-demand antimicrobial release for wound healing

Addressing the challenge of impaired wound healing caused by multidrug-resistant bacterial infections and excessive inflammation is vital for promoting tissue regeneration and preventing systemic infections. However, current antimicrobial agents often release continuously, even in uninfected or healing wounds, resulting in biological toxicity, oxidative stress, and delayed healing. Here, a composite nanomaterial is developed that could reversibly release on-demand antimicrobial agents, triggered by bacterial infection through the cascade assembly of thiol-modified chitooligosaccharide (SC) and silver nanoclusters (AgNCs). When bacteria invade the wound, SC dissociates the aggregated AgNCs through the protonation of amino groups, initiating the release of Ag⁺. Once the bacteria are eradicated, the AgNCs are encapsulated by negatively charged SC, preventing excessive release of Ag⁺, thereby minimizing the toxicity accumulation issue associated with traditional antibacterial treatments. This responsive release on-demand of antibacterial agents is reversible and exhibits excellent cycling stability with excellent anti-inflammation ability. In a methicillin-resistant Staphylococcus aureus (MRSA) wound model, AgNCs@SC achieves complete wound healing within 9 days, compared to 19.8 ± 1.4% in the control group. The distinct infection-adaptive design of this platform distinguishes it from prior static or irreversible antimicrobial systems and offers new insights into the development of safe and efficient antibacterial and anti-inflammatory materials. © 2026 Elsevier Inc.