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Current\u00a0treatments largely fail to address the dual demands of synovial anti\u2010inflammation and\u00a0cartilage anabolism, particularly under the critical yet often overlooked influence of\u00a0oxygen zonation within articular tissues. In this study, we propose a novel\u00a0microorganism oxygen metabolism engineering strategy using an injectable\u00a0cyanobacteria\u2010laden hydrogel (R\u2010alga) that enables light\u2010dependent dynamic oxygen\u00a0regulation to mimic native physiological oxygen gradients. Under infrared ray (red)\u00a0light\u00a0irradiation, cyanobacteria within R\u2010alga efficiently produce oxygen via photosynthesis,\u00a0specifically targeting and alleviating hypoxia in the inflamed synovial region. This\u00a0process significantly suppresses the aberrant expression of HIF\u20101\u03b1 in macrophages,\u00a0ameliorates their metabolic dysfunction, and effectively scavenges ROS, ultimately\u00a0inducing macrophage polarization toward an pro\u2010regenerative\u00a0phenotype. In the\u00a0absence of light, cyanobacteria within R\u2010alga actively consume oxygen through\u00a0respiration, creating and maintaining a physiologically relevant hypoxic\u00a0microenvironment in the cartilage defect area. This environment stabilizes HIF\u20101\u03b1\u00a0expression in chondrocytes, activates the HIF\u20101\u03b1\u2010DOT1L signaling axis, and\u00a0significantly enhances the biosynthesis of key cartilage matrix components, thereby\u00a0facilitating cartilage repair. Collectively, the microorganism oxygen metabolismengineering strategy offers a breakthrough for precise control of the\u00a0osteoarthritis microenvironment and therapy.<\/jats:p>","DOI":"10.1002\/advs.77248","type":"journal-article","created":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T11:31:58Z","timestamp":1788175918000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Engineered Cyanobacteria\u2010Hydrogel Microecological System for Oxygen Reprogramming Synergizes Immunomodulation With Anabolism in Osteoarthritis Therapy"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-9617-0229","authenticated-orcid":false,"given":"Lerong","family":"Yang","sequence":"first","affiliation":[{"name":"Guangxi Key Laboratory of Regenerative Medicine Guangxi Engineering Center in Biomedical Materials For Tissue and Organ Regeneration International Joint Laboratory On Regeneration of Bone and Soft Tissues Collaborative Innovation Center of Regenerative Medicine and Medical Bioresource Development and Application Co\u2010Constructed By the Province and Ministry The First Affiliated Hospital of Guangxi Medical University Guangxi Medical University  Nanning China"},{"name":"Department of Orthopaedics Affiliated Hospital of Guilin Medical University  Guilin Guangxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9709-7248","authenticated-orcid":false,"given":"Chong","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics Affiliated Hospital of Guilin Medical University  Guilin Guangxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongjun","family":"Huang","sequence":"additional","affiliation":[{"name":"Guangxi Key Laboratory of Regenerative Medicine Guangxi Engineering Center in Biomedical Materials For Tissue and Organ Regeneration International Joint Laboratory On Regeneration of Bone and Soft Tissues Collaborative Innovation Center of Regenerative Medicine and Medical Bioresource Development and Application Co\u2010Constructed By the Province and Ministry The First Affiliated Hospital of Guangxi Medical University Guangxi Medical University  Nanning China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siyi","family":"Liu","sequence":"additional","affiliation":[{"name":"Guangxi Key Laboratory of Regenerative Medicine Guangxi Engineering Center in Biomedical Materials For Tissue and Organ Regeneration International Joint Laboratory On Regeneration of Bone and Soft Tissues Collaborative Innovation Center of Regenerative Medicine and Medical Bioresource Development and Application Co\u2010Constructed By the Province and Ministry The First Affiliated Hospital of Guangxi Medical University Guangxi Medical University  Nanning China"},{"name":"Life Sciences Institute Guangxi Medical University  Nanning China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zeyu","family":"Huang","sequence":"additional","affiliation":[{"name":"Guangxi Key Laboratory of Regenerative Medicine Guangxi Engineering Center in Biomedical Materials For Tissue and Organ Regeneration International Joint Laboratory On Regeneration of Bone and Soft Tissues Collaborative Innovation Center of Regenerative Medicine and Medical Bioresource Development and Application Co\u2010Constructed By the Province and Ministry The First Affiliated Hospital of Guangxi Medical University Guangxi Medical University  Nanning China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Licheng","family":"Xi","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics Affiliated Hospital of Guilin Medical University  Guilin Guangxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9540-4734","authenticated-orcid":false,"given":"Huan","family":"Cao","sequence":"additional","affiliation":[{"name":"National Engineering Research Center for Biomaterials College of Biomedical Materials Sichuan University  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9666-0024","authenticated-orcid":false,"given":"Li","family":"Zheng","sequence":"additional","affiliation":[{"name":"Guangxi Key Laboratory of Regenerative Medicine Guangxi Engineering Center in Biomedical Materials For Tissue and Organ Regeneration International Joint Laboratory On Regeneration of Bone and Soft Tissues Collaborative Innovation Center of Regenerative Medicine and Medical Bioresource Development and Application Co\u2010Constructed By the Province and Ministry The First Affiliated Hospital of Guangxi Medical University Guangxi Medical University  Nanning China"},{"name":"Yida collaborative Medical Technology Co., Ltd. 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