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Effective intervention requires strategies that not only eliminate pathogens but also modulate the dysregulated oxidative microenvironment. Hydrogen (H\n                    <jats:sub>2<\/jats:sub>\n                    ) therapy holds promise in periodontitis immunotherapy due to its exceptional safety profile and unique selective antioxidant properties. Here, we present a tailored biomaterial platform\u2014Magnesium hydride (MgH\n                    <jats:sub>2<\/jats:sub>\n                    )\u2010Poly(lactic\u2010co\u2010glycolic acid) (PLGA)@Oxygen\u2010deficient titanium dioxide (TiO\n                    <jats:sub>2\u2010x<\/jats:sub>\n                    )\u2010Alginate core\u2013shell microspheres (MTMs)\u2014fabricated via coaxial electrostatic microdroplet technology for localized periodontitis therapy. This system provides rapid antibacterial activity together with sustained remodeling of the local tissue microenvironment. The MTMs achieve long\u2010term antioxidant and anti\u2010inflammatory effects through the synergistic sustained release of hydrogen molecules and Mg\n                    <jats:sup>2+<\/jats:sup>\n                    ions (up to 7 days). Concurrently, the surface\u2010etched TiO\n                    <jats:sub>2\u2212x<\/jats:sub>\n                    particles embedded in the shell layer, exhibiting peroxidase\u2010like catalytic activity, enable rapid antibacterial effects in the presence of low\u2010level exogenous hydrogen peroxide. In vitro, MTMs attenuated oxidative stress in periodontal ligament stem cells and promoted lipopolysaccharide\u2010stimulated macrophages to polarize from pro\u2010inflammatory M1 toward reparative M2 phenotypes. In a rat periodontitis model, short\u2010term treatment (1 week) reduced bacterial load, mitigated inflammation, and inhibited bone resorption, while long\u2010term application (1 month) promoted bone repair and remodeling. These findings demonstrate that MTMs represent a powerful therapeutic platform for periodontitis and hold potential for broader biomedical applications.\n                  <\/jats:p>","DOI":"10.1002\/adhm.202504793","type":"journal-article","created":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T13:22:53Z","timestamp":1774876973000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Core\u2013Shell Microspheres Enabling Sustained Hydrogen Release and Peroxidase\u2010Like Catalytic Activity for Periodontitis Therapy"],"prefix":"10.1002","volume":"15","author":[{"given":"Xinzhi","family":"Tan","sequence":"first","affiliation":[{"name":"State Key Laboratory of Oral Diseases National Center for Stomatology National Clinical Research Center for Oral Diseases Engineering Research Center of Oral Translational Medicine Ministry of Education National Engineering Laboratory for Oral Regenerative Medicine West China 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