{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T20:29:22Z","timestamp":1792182562211,"version":"4.4.0"},"reference-count":46,"publisher":"Wiley","issue":"36","license":[{"start":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T00:00:00Z","timestamp":1787097600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T00:00:00Z","timestamp":1787097600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Adv Healthcare Materials"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Remodeling the immune microenvironment and scavenging excess reactive oxygen species (ROS) are considered effective strategies for treating rheumatoid arthritis (RA). Methotrexate (MTX), a first\u2010line drug, can correct the imbalance between helper T\u2010cell type 17 and regulatory T cells (Th17\/Treg) and inhibit the proliferation and migration of fibroblast\u2010like synoviocytes (FLSs). However, it lacks antioxidant and macrophage regulatory functions, is prone to systemic toxicity, and has poor solubility. In this study, MTX and oxidized\n                    <jats:italic>Bletilla striata<\/jats:italic>\n                    polysaccharide (OBSP) were conjugated and self\u2010assembled into MTX\u2010ss\u2010OBSP NPs via disulfide bonds to integrate macrophage\u2010polarizing and antioxidant activities. These nanoparticles were loaded into a novel ROS\u2010responsive oxidized hyaluronic acid\u20103\u2010aminophenylboronic acid\u2013hyaluronic acid (OHA\u2010PBA\u2010HA) hydrogel, yielding MTX\u2010ss\u2010OBSP NPs@OHA\u2010PBA\u2010HA. This injectable hydrogel exhibits ROS\u2010triggered drug release, reduces ROS levels, promotes M2 macrophage polarization, and modulates cytokine secretion (decreasing IL\u20106\/TNF\u2010\u03b1; increasing IL\u201010). In vivo experiments demonstrated that the hydrogel blocks bone erosion, inhibits synovial inflammation, protects cartilage, and regulates M1\/M2 and Th17\/Treg balances while significantly reducing MTX\u2010induced hepatotoxicity and nephrotoxicity. Compared with free MTX, this nanoparticle\u2010loaded hydrogel accelerates the resolution of RA inflammation with superior safety. Therefore, this responsive hydrogel system represents a promising candidate for clinical RA treatment by integrating immune remodeling and antioxidant therapy.\n                  <\/jats:p>","DOI":"10.1002\/adhm.71627","type":"journal-article","created":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T05:27:53Z","timestamp":1787203673000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["ROS\u2010Sensitive Hydrogel With Methotrexate\u2010ss\u2010Oxidized\n                    <i>Bletilla striata<\/i>\n                    Polysaccharide Nanoparticles for the Enhanced Treatment of Rheumatoid Arthritis"],"prefix":"10.1002","volume":"15","author":[{"given":"Rui","family":"Ma","sequence":"first","affiliation":[{"name":"College of Pharmacy Qiqihar Medical University  Qiqihar 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