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Here, we report a structurally defined, pentakis\u2010PEGylated fullerene derivative, termed FPEG\n                    <jats:sub>5<\/jats:sub>\n                    , which exhibits dual functionality as a potent reactive oxygen species (ROS) scavenger and an immunomodulator. Beyond its antioxidant activity, FPEG\n                    <jats:sub>5<\/jats:sub>\n                    directly targets glycogen synthase kinase\u20103\u03b2 (GSK\u20103\u03b2), thereby stabilizing \u03b2\u2010catenin and suppressing the Nuclear Factor kappa\u2010B (NF\u2010\u03baB) inflammatory axis. This dual\u2010action mechanism effectively reprograms macrophages from a pro\u2010inflammatory (M1) to a pro\u2010regenerative (M2) phenotype under diabetic conditions. To enable localized therapy, FPEG\n                    <jats:sub>5<\/jats:sub>\n                    is incorporated into an injectable, glucose\u2010 and ROS\u2010responsive hydrogel for on\u2010demand release. This combination effectively reshapes the local immune microenvironment, restores osteogenic differentiation in vitro, and drives robust, bridging bone regeneration in a diabetic calvarial defect model. This work presents a novel therapeutic strategy integrating a target\u2010specific fullerene pharmacophore with a smart delivery system for diabetic osteoregeneration.\n                  <\/jats:p>","DOI":"10.1002\/adma.202600033","type":"journal-article","created":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T06:10:12Z","timestamp":1778825412000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["A Dual\u2010Targeting Strategy Against ROS and GSK\u20103\u03b2 With a PEGylated Fullerene\/Smart Hydrogel Synergistic System for Diabetic Bone Regeneration"],"prefix":"10.1002","volume":"38","author":[{"given":"Yijun","family":"Wang","sequence":"first","affiliation":[{"name":"Key Laboratory of Molecular Nanostructure and Nanotechnology &amp; Beijing National Laboratory For Molecular Sciences Institute of Chemistry Chinese Academy of Sciences  Beijing P.R. 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