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Herein, we develop a bioadhesive scaffold integrating inflammation\u2010responsive methotrexate (MTX) nanoparticles and chondrogenic miRNA\u2010140 delivery systems for synergistic immunomodulation and osteochondral regeneration in advanced RA. The adhesive scaffold matrix consists of collagen and polydopamine\u2010modified\u2010hyaluronic acid (PDA\/HA), crosslinked with polyethylene glycol diglycidyl ether (PEGDE), which provides robust mesenchymal stem cell adhesion and prolongs nanomedicine retention while establishing a regenerative microenvironment. The engineered system features MMP\u2010labile polydopamine\u2010doped lipid nanoparticles (PLNP) that rapidly release MTX in inflammatory conditions to suppress synovitis, working in concert with reactive oxygen species\u2010scavenging gallic acid\u2010modified chitosan nanoparticles (GC) that protect and effectively deliver miRNA\u2010140 to restore chondrogenesis. In collagen\u2010induced advanced arthritis models, this dual\u2010stage therapy demonstrated sequential therapeutic action by initial immunomodulation followed by structural regeneration, yielding complete osteochondral restoration characterized by hyaline cartilage formation with physiological matrix features and integrated subchondral bone restoration. This work represents a significant progress in advanced RA treatment by transitioning from symptomatic management to true disease modification, combining precise immunomodulation with functional tissue regeneration through intelligent biomaterial design.<\/jats:p>","DOI":"10.1002\/smll.202511882","type":"journal-article","created":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T14:25:36Z","timestamp":1770733536000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Bioadhesive Scaffold for Dual Delivery of Methotrexate\u2010Loaded Liposomes and Chondrogenic miRNA in Advanced Rheumatoid Arthritis Therapy"],"prefix":"10.1002","volume":"22","author":[{"given":"Yuelin","family":"Hu","sequence":"first","affiliation":[{"name":"Institute of Biomedical Engineering College of Medicine Southwest Jiaotong University  Chengdu Sichuan China"},{"name":"Key Laboratory of Advanced Technologies of Materials Ministry of Education 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