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Drawing inspiration from natural antioxidases, the\n                    <jats:italic>de novo<\/jats:italic>\n                    design of an interlaminar ruthenium\u2010coordinated covalent organic framework (COF) is reported that functions as an artificial antioxidase system. This fully condensed COF architecture (TTf\u2010Ru) combines extended \u03c0\u2010electron delocalization with precisely engineered asymmetric ruthenium coordination sites, thereby creating optimal electronic environments for scavenging reactive oxygen species (ROS). Spectroscopic and computational analyses reveal that TTf\u2010Ru exhibits dual enzyme\u2010mimetic activities, demonstrating both catalase\u2010 and superoxide dismutase\u2010like functionality through tailored adsorption energetics for oxygen intermediates. At the cellular level, TTf\u2010Ru effectively mitigates oxidative stress in mesenchymal stem cells, preserving their osteogenic differentiation capacity even under pro\u2010inflammatory conditions. The artificial antioxidase simultaneously orchestrates an immunomodulatory response, suppressing pro\u2010inflammatory macrophage polarization while promoting a tissue\u2010reparative phenotype. In periodontitis models, this coordinated action translates to significant therapeutic outcomes, which reduce alveolar bone resorption and maintain periodontal tissue architecture. The findings establish a material design paradigm for COF\u2010based enzyme mimics, highlighting how spatially organized biocatalytic centers can be engineered to address multifactorial diseases through integrated redox modulation and immune regulation, which provides new possibilities for treating ROS\u2010mediated inflammatory disorders.\n                  <\/jats:p>","DOI":"10.1002\/adma.202514915","type":"journal-article","created":{"date-parts":[[2025,10,24]],"date-time":"2025-10-24T12:18:33Z","timestamp":1761308313000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Covalent Organic Framework\u2010Based Artificial Antioxidases with \u03c0\u2010Electron Delocalization and Asymmetric Coordination Sites for Superior Inflammation Inhibition and Oral Bone Modulation"],"prefix":"10.1002","volume":"38","author":[{"given":"Yichun","family":"Qin","sequence":"first","affiliation":[{"name":"State Key Laboratory of Oral 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