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To address these, we developed a \u201cHydrogen\/Magnesium dual\u2010engine microneedle\u201d (MN\u2010Mg) system by embedding magnesium (Mg) microparticles within a methacrylated hyaluronic acid (HAMA) hydrogel matrix via micromolding. Possessing high mechanical strength, Mg\u2010MNs penetrate the dura mater. Upon implantation, the system triggers a controllable magnesium\u2010water reaction, initiating a spatiotemporally synergistic dual\u2010engine therapeutic mode. The \u201chydrogen engine\u201d rapidly releases high\u2010concentration hydrogen gas (H\n                    <jats:sub>2<\/jats:sub>\n                    ) during the acute SCI phase. It efficiently scavenges ROS storm (reducing levels by 55%) by inhibiting the MAPK pathway and downregulating AP\u20101 transcription, creating an antioxidant window for neural repair. Subsequently, the \u201cmagnesium engine\u201d provides sustained Mg\n                    <jats:sup>2<\/jats:sup>\n                    <jats:sup>+<\/jats:sup>\n                    release during the subacute phase, exerting a dual restorative effect: induces microglia polarization toward the pro\u2010reparative M2 phenotype (4.8\u2010fold increase) and promotes axonal regeneration (2.9\u2010fold increase). This synergy leads to locomotor recovery in a rat SCI model, with scores improving from 5.5 \u00b1 1.05 (Controls) to 14.8 \u00b1 1.17 at 8 weeks. This \u201cPenetration\u2010Confinement\u2010Dual\u2010Engine Modulation\u201d paradigm enables spatiotemporal synergistic H2\/Mg therapy\u00a0supported by an elucidated ROS\u2010MAPK\/AP\u20101 regulatory axis, advancing SCI treatment from symptomatic relief to targeted neural microenvironment reconstruction.\n                  <\/jats:p>","DOI":"10.1002\/smll.202514854","type":"journal-article","created":{"date-parts":[[2026,2,16]],"date-time":"2026-02-16T08:07:06Z","timestamp":1771229226000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Spatiotemporal Co\u2010Delivery of Hydrogen and Magnesium via Microneedle Patches for Neuroinflammation Modulation After Spinal Cord Injury: A Multi\u2010Modal In Vivo Study"],"prefix":"10.1002","volume":"22","author":[{"given":"Haibo","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Orthopedics First Affiliated Hospital of Soochow University Orthopedic Institute Soochow University  Suzhou Jiangsu P. 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