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Therefore, an effective OA treatment strategy should simultaneously enhance joint long-term lubrication and suppress inflammation. Toward this goal, we developed durable Lipo\/PADM microgels via multiple cross-linking to integrate sustained lubrication with matrix metalloproteinase (MMP)-responsive dexamethasone release. The microgels maintained a low coefficient of friction of 0.029, remaining 24.3% lower than PBS after 8 weeks of in vitro degradation. In the MMP-rich OA microenvironment, ester-bond cleavage enabled sustained, on-demand drug release, reaching 70% within 14 days. Lipo\/PADM microgels restored type II collagen expression, suppressed MMP-13 in bone marrow mesenchymal stem cells, and alleviated the OA-associated catabolic microenvironment. Intra-articular administration significantly reduced cartilage degeneration and delayed OA progression. These poly(glutamic acid)-based microgels offer a promising OA therapy through durable lubrication, responsive drug delivery, and prolonged intra-articular retention.<\/jats:p>","DOI":"10.1021\/acs.biomac.6c00920","type":"journal-article","created":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T08:01:28Z","timestamp":1787212888000},"page":"6058-6073","source":"Crossref","is-referenced-by-count":1,"title":["Poly(\n                    <scp>l<\/scp>\n                    -glutamic Acid)-Based Microgels\nwith Long-Term Synergistic Lubrication and MMP-Responsive Anti-Inflammatory\nDelivery for Osteoarthritis Therapy"],"prefix":"10.1021","volume":"27","author":[{"given":"Rong","family":"Wu","sequence":"first","affiliation":[{"name":"Shanghai University , , ,","place":["Shanghai, P.R. China, 200444"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanyang","family":"Chen","sequence":"additional","affiliation":[{"name":"Shanghai Jiao Tong University School of Medicine , , 197 Ruijin Second Road , ,","place":["Shanghai, P. R. China, 200025"]},{"name":"The First Affiliated Hospital of Bengbu Medical University , , ,","place":["Bengbu, China, 233004"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junyu","family":"Wu","sequence":"additional","affiliation":[{"name":"Shanghai University , , ,","place":["Shanghai, P.R. China, 200444"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9533-5898","authenticated-orcid":true,"given":"Kaixuan","family":"Ren","sequence":"additional","affiliation":[{"name":"Shanghai University , , ,","place":["Shanghai, P.R. 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