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A pressing challenge is to effectively enhance the regenerative microenvironment at different stages of the healing process, tailoring interventions as needed. Here, a dual enzyme mimetic and bacterial responsive self\u2010activating antimicrobial hydrogel designed to enhance IPUs healing is introduced. This hydrogel incorporates pH\u2010responsive dual enzyme\u2010active nanoplatforms (HNTs\u2010Fe\u2010Ag) encapsulated within a methacrylate\u2010modified silk fibroin (SFMA) and dopamine methacrylamide (DMA) matrix. This composite hydrogel exhibits adaptive microenvironment regulation capabilities. Under the low pH microenvironment of bacterial infection, it has excellent antimicrobial activity by self\u2010activating the \u2022OH generation in conjunction with photothermal effects. Under the neutral and alkaline microenvironment of chronic inflammation, it catalyzes the decomposition of hydrogen peroxide (H\n                    <jats:sub>2<\/jats:sub>\n                    O\n                    <jats:sub>2<\/jats:sub>\n                    ) to produce oxygen (O\n                    <jats:sub>2<\/jats:sub>\n                    ), thereby alleviating hypoxia and scavenging reactive oxygen species (ROS), which in turn remodulates the phenotype of macrophages. The composite hydrogel demonstrates on\u2010demand therapeutic effects in the microenvironment of infected wounds, significantly enhancing the regenerative microenvironment of IUPs by promoting wound closure, inflammation regulation, and collagen deposition through self\u2010activated antimicrobial action during infection and adaptive hypoxia relief during recovery. This approach offers a novel strategy for developing smart wound dressings.\n                  <\/jats:p>","DOI":"10.1002\/adhm.202402363","type":"journal-article","created":{"date-parts":[[2024,10,11]],"date-time":"2024-10-11T02:55:56Z","timestamp":1728615356000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Double Enzyme Active Hydrogel Program Regulates the Microenvironment of\n                    <i>Staphylococcus aureus<\/i>\n                    \u2010Infected Pressure Ulcers"],"prefix":"10.1002","volume":"14","author":[{"given":"Hailin","family":"Xie","sequence":"first","affiliation":[{"name":"School of Resource &amp; Environment and Safety Engineering Hunan University of Science and Technology  Xiangtan 411201 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuna","family":"Qian","sequence":"additional","affiliation":[{"name":"National Engineering Research Center of Ophthalmology and 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