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However, no therapeutics specifically targeting AGEs are developed for DOA treatment. Here, a composite hydrogel (PTC\u2010MP) incorporated with polydopamine\u2010coated tannic cerium (PTC) nanozymes and magnesium ions (Mg\n                    <jats:sup>2+<\/jats:sup>\n                    ), implementing a strategy of \u201crestrain\u2010restore\u2010reinforce (3R)\u201d for AGEs\u2010directed DOA therapy is reported. PTC\u2010MP hydrogel effectively restrains the formation of AGEs by scavenging free radicals, chelating ferrous ions, and competitive hydrophobic site binding. By leveraging mild photothermal therapy (mPTT), PTC\u2010MP hydrogel restores cartilage homeostasis by reducing AGEs\u2010induced reactive oxygen species (ROS) overproduction and mitochondrial dysfunction. Furthermore, Mg\n                    <jats:sup>2+<\/jats:sup>\n                    in PTC\u2010MP hydrogel reinforces joint repair by stimulating endogenous hyaluronic acid (HA) secretion to improve lubrication. In a rat DOA model, PTC\u2010MP hydrogel with mPTT significantly attenuated DOA progression, reduced osteophytes formation and synovial inflammation, and improved motor function. Therefore, the \u201c3R\u201d strategy targeting AGEs provides a promising therapeutic approach for recalcitrant DOA.\n                  <\/jats:p>","DOI":"10.1002\/advs.202516389","type":"journal-article","created":{"date-parts":[[2025,12,5]],"date-time":"2025-12-05T11:34:42Z","timestamp":1764934482000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Nanozyme\u2010Integrated Hydrogel Targeting AGEs for Diabetic Osteoarthritis Therapy"],"prefix":"10.1002","volume":"13","author":[{"given":"Rui","family":"Chen","sequence":"first","affiliation":[{"name":"Key Laboratory of Marine Drugs Ministry of Education Shandong Key Laboratory of Glycoscience and Glycotherapeutics School of Medicine and Pharmacy Ocean University of China  Qingdao 266003 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanguo","family":"Su","sequence":"additional","affiliation":[{"name":"Key Laboratory of Marine Drugs Ministry 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