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Here, we developed a locally injectable, ROS\u2010scavenging, and ROS\u2010\/pH\u2010responsive drug\u2010delivery platform (HC@PTM) by bio\u2010compositing of aldolizing hyaluronic acid (HA) crosslinked with chitosan (CS), and ROS\u2010triggered\/eliminated micelles (PTM) coupled with the drug methotrexate(MTX). The PTM efficiently eradicate excessive ROS in RA\u2010joints, precisely triggering drug\u2010release within inflamed arthritic\u2010sites and further confer exceptional antioxidant origins to HC@PTM. HC@PTM with outstanding shape\u2010adaptability and self\u2010repairing properties effectively conformed to irregular articular cartilage while resisting joint\u2010induced deformations. Further, the platform's pH\u2010responsive nature enables on\u2010demand drug\u2010release within acidic inflamed synovium, serving as a drug\u2010reservoir for precise and sustained therapeutic effects. Extensive in vitro and in vivo investigations confirm HC@PTM's ability to induce M2 macrophage polarization, downregulate inflammatory factor expression, and ameliorate the RA\u2010microenvironment, ultimately achieving synergistic therapeutic outcomes. This study represents significant advancements in precise and long\u2010term RA\u2010treatment through a minimally invasive approach, offering potential strategies for novel precision medicine.<\/jats:p>","DOI":"10.1002\/adhm.202403579","type":"journal-article","created":{"date-parts":[[2024,12,4]],"date-time":"2024-12-04T04:39:22Z","timestamp":1733287162000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Locally Injectable, ROS\u2010Scavenging, and ROS\u2010\/pH\u2010Responsive Polymeric\u2010Micelles\u2010Embedded Hydrogels for Precise Minimally Invasive and Long\u2010Lasting Rheumatoid Therapy"],"prefix":"10.1002","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0286-2061","authenticated-orcid":false,"given":"Xinhua","family":"Liu","sequence":"first","affiliation":[{"name":"Institute of Biomass &amp; Functional Materials Shaanxi University of Science &amp;Technology  Xi'an 710021 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xing","family":"Chen","sequence":"additional","affiliation":[{"name":"College of Bioresources Chemical and Materials Engineering Shaanxi University of Science &amp; Technology  Xi'an 710021 China"},{"name":"Institute of Biomass &amp; Functional Materials Shaanxi University of Science &amp;Technology  Xi'an 710021 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yifan","family":"Fei","sequence":"additional","affiliation":[{"name":"College of Bioresources Chemical and Materials Engineering Shaanxi University of Science &amp; Technology  Xi'an 710021 China"},{"name":"Institute of Biomass &amp; Functional Materials Shaanxi University of Science &amp;Technology  Xi'an 710021 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiamin","family":"Zhang","sequence":"additional","affiliation":[{"name":"College of Bioresources Chemical and Materials Engineering Shaanxi University of Science &amp; Technology  Xi'an 710021 China"},{"name":"Institute of Biomass &amp; Functional Materials Shaanxi University of Science &amp;Technology  Xi'an 710021 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ouyang","family":"Yue","sequence":"additional","affiliation":[{"name":"Institute of Biomass &amp; Functional Materials Shaanxi University of Science &amp;Technology  Xi'an 710021 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuechuan","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute of Biomass &amp; Functional Materials Shaanxi University of Science &amp;Technology  Xi'an 710021 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huie","family":"Jiang","sequence":"additional","affiliation":[{"name":"College of Bioresources Chemical and Materials Engineering Shaanxi University of Science &amp; Technology  Xi'an 710021 China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,12,4]]},"reference":[{"key":"e_1_2_8_1_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10238-024-01359-3"},{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40744-020-00252-1"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2665-9913(23)00211-4"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2665-9913(23)00240-0"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.01930"},{"key":"e_1_2_8_6_1","first-page":"48","volume":"335","author":"Li J.","year":"2021","journal-title":"J. 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