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Herein, this work presents an acoustically triggered carbon monoxide (CO) depot based on rigid\u2010flexible integrated polymer networks that are engineered for high\u2010capacity storage and sustained release of CO for infection\u2010to\u2010regeneration. This depot is architected by embedding CO precursor\u2010loaded metallized covalent organic framework quantum dots (COFQDs) into a decellularized extracellular matrix (ECM) gel network derived from small intestinal submucosa (SIS). The rigid COFQDs with abundant Mn sites enable substantial CO storage after ultrasound, while the flexible ECM acts as a gate that slowly enzymatically degrades for CO release up to 10 days. Upon ultrasound activation, the depot eradicates pathogens via sonodynamic therapy, while the liberated CO suppresses the NF\u2011\u03baB\/MAPK\/IRF3 axes to remodel inflammation and synergizes with SIS\u2011derived growth factors to initiate tissue regeneration. In a murine methicillin\u2010resistant\n                    <jats:italic>Staphylococcus aureus<\/jats:italic>\n                    (MRSA)\u2010infected wound model, this depot fulfilled superior scarless healing compared to conventional treatments. This rigid\u2010flexible synergistic design establishes a compelling paradigm for temporally regulated anti\u2010infective therapy, offering a promising strategy for managing MDR diseases.\n                  <\/jats:p>","DOI":"10.1002\/advs.76681","type":"journal-article","created":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T12:19:05Z","timestamp":1784549945000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Harmonizing Rigidity and Flexibility: Embedding COF Quantum Dots Into Extracellular Matrix Gel as Carbon Monoxide Depot for Acoustically Triggered Time\u2010Programmable Anti\u2010Infective Therapy"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-4109-4093","authenticated-orcid":false,"given":"Baohong","family":"Sun","sequence":"first","affiliation":[{"name":"Interdisciplinary Eye Research Institute (EYE\u2010X Institute) Anhui Engineering Technology Research Center 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