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Iron, which is essential for bacterial metabolism and immune cell functions, is extremely important. Bacteria harness iron from nearby cells to promote biofilm formation, ensuring their survival. Iron deficiency within the infection microenvironment (IME) consequently hampers macrophage function, enabling further dissemination of the infection and hindering macrophage polarization to the M2 phenotype. Therefore, a novel approach is proposed to regulate macrophage polarization, aiming to restore the inflammatory immune environment. A composite hydrogel derived from natural polymers is developed to address infections and manage iron metabolism in macrophages. This IME\u2010responsive hydrogel, named FCL\u2010ECMH, is synthesized by encapsulating vermiculite functional core layers within a decellularized extracellular matrix hydrogel. It is noteworthy that FCL\u2010ECMH can produce reactive oxygen species within the IME. Supplementary photothermal treatment enhances bacterial iron uptake, leading to ferroptosis\u2010like death. This process also rejuvenates the iron\u2010enriched macrophages around the IME, thereby enhancing their antibacterial and tissue repair functions. In vivo experiments confirmed the antibacterial and repair\u2010promoting capabilities of FCL\u2010ECMH, indicating its potential for clinical applications.<\/jats:p>","DOI":"10.1002\/advs.202309820","type":"journal-article","created":{"date-parts":[[2024,6,19]],"date-time":"2024-06-19T15:10:08Z","timestamp":1718809808000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["A Multifunctional Tissue\u2010Engineering Hydrogel Aimed to Regulate Bacterial Ferroptosis\u2010Like Death and Overcoming Infection Toward Bone Remodeling"],"prefix":"10.1002","volume":"11","author":[{"given":"Renjie","family":"Lu","sequence":"first","affiliation":[{"name":"Department of Orthopedic Surgery, Shanghai Institute of Microsurgery on Extremities Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine  600 Yishan Road Shanghai 200233 China"},{"name":"Nanomedicine and Intestinal Microecology Research 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