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Herein, jaw vascular unit (JVU)\u2010biomimetic nanozymes are developed by coating Mn\/Ca diatomic sites nanozymes (Mn\u2010CaDSN) with hybrid membranes (HM) from M2 macrophages and osteogenically induced human bone marrow mesenchymal stem cells (HBMSCs). Mn\u2010CaDSN exhibited synergistic superoxide dismutase\u2010like, catalase\u2010like, and glutathione peroxidase (GPx)\u2010like activities,\u00a0and the maximized GPx\u2010like catalytic activity of Mn\u2010CaDSN (\n                    <jats:italic>V<\/jats:italic>\n                    <jats:sub>max<\/jats:sub>\n                    = 0.69 m\n                    <jats:sc>m<\/jats:sc>\n                    \u00b7min\n                    <jats:sup>\u22121<\/jats:sup>\n                    ) is 2.1\u2010fold higher than Mn single\u2010atom controls (\n                    <jats:italic>V<\/jats:italic>\n                    <jats:sub>max<\/jats:sub>\n                    = 0.33 m\n                    <jats:sc>m<\/jats:sc>\n                    \u00b7min\n                    <jats:sup>\u22121<\/jats:sup>\n                    ). Density functional theory calculations revealed that Ca sites optimized substrate adsorption and O\u2500H bond cleavage via d\u2010band center modulation. HM coating enabled targeted JVU delivery, enhancing cellular uptake and reprogramming irradiated macrophages toward M2 polarization (ARG\u20101\n                    <jats:sup>+<\/jats:sup>\n                    cells increasing 3.8\u2010fold) and osteogenic differentiation (ALP area uprising 4.2\u2010fold). In irradiated cells, the nanozymes concurrently eliminated reactive oxygen\/nitrogen species (RONS), activates mitophagy (mitochondrial\u2010lysosomal colocalization colocalization uprising 50%), and suppresses cuproptosis (HSP70 decreasing 45%; intracellular Cu\n                    <jats:sup>2+<\/jats:sup>\n                    decreasing 30%). Loaded Dl\u20103\u2010n\u2010butylphthalide (NBP) further enhanced angiogenesis in vivo. In rat ORNJ models, NBP@Mn\u2010CaDSN@HM promoted mucosal healing and increased bone volume fraction (BV\/TV increasing 2.3\u2010fold vs irradiated controls) by rebalancing immune\u2010vascular\u2010osteogenic microenvironments. This work establishes a paradigm of JVU biomimetics integrated with diatomic nanozymes for comprehensive ORNJ therapy.\n                  <\/jats:p>","DOI":"10.1002\/adma.202517968","type":"journal-article","created":{"date-parts":[[2025,11,14]],"date-time":"2025-11-14T11:23:08Z","timestamp":1763119388000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Diatomic Mn\/Ca Nanozymes with Jaw Vascular Unit Mimicry for Triple\u2010Enzyme Synergistic Therapy of Osteoradionecrosis"],"prefix":"10.1002","volume":"38","author":[{"given":"Ziyu","family":"Chen","sequence":"first","affiliation":[{"name":"Medical Basic Research Innovation Centre for Cardiovascular and Cerebrovascular Diseases Ministry of Education International Joint Laboratory for Drug Target of Critical Illnesses School of Pharmacy Nanjing Medical University  Nanjing Jiangsu 211166 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University)  Nanjing Jiangsu 210029 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jikang","family":"Cao","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery The Affiliated Stomatological Hospital of Nanjing Medical University State Key Laboratory Cultivation Base of Research Prevention and Treatment for Oral Diseases (Nanjing Medical University) Jiangsu Province Engineering Research Centre of Stomatological Translational Medicine (Nanjing Medical University)  Nanjing Jiangsu 210029 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huijun","family":"Jiang","sequence":"additional","affiliation":[{"name":"Medical Basic Research Innovation Centre for Cardiovascular and Cerebrovascular Diseases Ministry of Education International Joint Laboratory for Drug Target of Critical Illnesses School of Pharmacy Nanjing Medical University  Nanjing Jiangsu 211166 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