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Under hyperglycemic conditions, the immune microenvironment fails to switch between the pro\u2010inflammatory environment required for pathogen clearance and the anti\u2010inflammatory environment for osteogenesis. Here, a glucose\u2010responsive hydrogel (PEG\u2010ZnO\u2010sita) is developed by integrating zinc oxide (ZnO) and sitagliptin into a network formed by dopamine\u2010modified tetra\u2010armed poly(ethylene glycol) succinimidyl glutarate (DA\u2010PEG\u2010SG) and phenylboronic acid\u2010modified gelatin (PBA\u2010Gel). PEG\u2010ZnO\u2010sita, enabled by amidation, phenylboronic ester bonds, and metal\u2010catechol coordination, confers rapid gelation, injectability, mechanical stability, self\u2010healing, and robust tissue adhesion, adapting to the local complexity at the bone defect. In a diabetic microenvironment, the rapid breakage of boronate ester bonds triggers the early burst release of Zn\n                    <jats:sup>2+<\/jats:sup>\n                    to inhibit infection by promoting M1 polarization, along with sitagliptin\u2010intervening glucose regulation. Whereafter, the sustained Zn\n                    <jats:sup>2+<\/jats:sup>\n                    and sitagliptin release induce M2 polarization and facilitate osteogenic differentiation, demonstrating a self\u2010adaptive strategy in response to inflammatory environments. Both in vitro and in vivo studies confirm that PEG\u2010ZnO\u2010sita effectively promotes bone regeneration by local hyperglycemic microenvironment modulation and sequential regulation of macrophage polarization. So, this temporal immunoregulation of hyperglycemia\u2010immune\u2010osteogenic cascade presents a promising strategy for diabetic infected bone defects.\n                  <\/jats:p>","DOI":"10.1002\/adhm.71581","type":"journal-article","created":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T03:38:21Z","timestamp":1786592301000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["A Self\u2010Adaptive Programming Strategy Enables Local Microenvironment Modulation and Temporal Immunomodulation for Diabetic Infected Bone Regeneration"],"prefix":"10.1002","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-0454-2215","authenticated-orcid":false,"given":"Xiaoyang","family":"Ding","sequence":"first","affiliation":[{"name":"Department of Orthodontics Peking University School and Hospital of Stomatology  Beijing China"},{"name":"National Centre of Stomatology National Clinical Research Center for Oral 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