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Adv."],"published-print":{"date-parts":[[2026,6,26]]},"abstract":"<jats:p>\n                    Osteoporotic fracture healing is impaired by dysregulated immune responses characterized by a T\n                    <jats:sub>H<\/jats:sub>\n                    1\/M1-biased inflammatory microenvironment. In this study, we show that extracellular magnesium ions (Mg\n                    <jats:sup>2+<\/jats:sup>\n                    ) reshape this osteo-immune niche in a dose- and time-dependent manner. Briefly, Mg\n                    <jats:sup>2+<\/jats:sup>\n                    suppresses TRPM7-mediated Ca\n                    <jats:sup>2+<\/jats:sup>\n                    spikes and the NFATc1-driven proinflammatory axis, thereby promoting T\n                    <jats:sub>H<\/jats:sub>\n                    2\/M2 responses. However, sustained excess Mg\n                    <jats:sup>2+<\/jats:sup>\n                    attenuates T\n                    <jats:sub>H<\/jats:sub>\n                    2\/M2 responses by inhibiting Orai1\/CaV-dependent Ca\n                    <jats:sup>2+<\/jats:sup>\n                    influx and reactivating T\n                    <jats:sub>H<\/jats:sub>\n                    1\/M1 responses through JAK-STAT1 signaling under low-calcium stimulation condition. To therapeutically use these dynamics, we engineered a bioceramic intramedullary nail (IMN) with a precisely controlled Mg\n                    <jats:sup>2+<\/jats:sup>\n                    release profile, delivering Mg\n                    <jats:sup>2+<\/jats:sup>\n                    in a time-phased manner. In an ovariectomized mouse fracture model, this optimized IMN reduced T\n                    <jats:sub>H<\/jats:sub>\n                    1\/M1 of early phase proinflammatory cells, enhanced T\n                    <jats:sub>H<\/jats:sub>\n                    2\/M2 responses during the remodeling phase, and supported coordinated immune regulation during osteoporotic fracture healing. These findings identify time-phased Mg\n                    <jats:sup>2+<\/jats:sup>\n                    delivery as a strategy to mitigate excessive inflammatory responses through temporal immunomodulation of CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells during osteoporotic bone healing.\n                  <\/jats:p>","DOI":"10.1126\/sciadv.aeb2091","type":"journal-article","created":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T17:59:33Z","timestamp":1782496773000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":1,"title":["Temporal immunomodulation of CD4\n                    <sup>+<\/sup>\n                    T cells by magnesium regulates osteoimmune responses in osteoporotic fracture healing"],"prefix":"10.1126","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7113-5170","authenticated-orcid":true,"given":"Jung Hun","family":"Kim","sequence":"first","affiliation":[{"name":"School of Chemical and Biological Engineering, the Institute of Chemical Processes, Seoul National University, Seoul 08826, Republic of Korea."},{"name":"Institute of Engineering Research, Seoul National University, Seoul 08826, Republic of Korea."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-9901-9438","authenticated-orcid":true,"given":"Tae Hoon","family":"Kang","sequence":"additional","affiliation":[{"name":"Interdisciplinary Program in Bioengineering, Seoul National University, Seoul 08826, Republic of Korea."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"SuWan","family":"Jeon","sequence":"additional","affiliation":[{"name":"Interdisciplinary Program in Bioengineering, Seoul National University, Seoul 08826, Republic of Korea."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3735-7727","authenticated-orcid":true,"given":"Nathaniel S.","family":"Hwang","sequence":"additional","affiliation":[{"name":"School of Chemical and Biological Engineering, the Institute of Chemical Processes, Seoul National University, Seoul 08826, Republic of Korea."},{"name":"Institute of Engineering Research, Seoul National University, Seoul 08826, Republic of Korea."},{"name":"Interdisciplinary Program in Bioengineering, Seoul National University, Seoul 08826, Republic of Korea."},{"name":"BioMAX\/N-Bio Institute, Institute of BioEngineering, Seoul National University, Seoul 08826, Republic of 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