biostudies-literatureCai LNational Natural Science Foundation of China174https://www.ebi.ac.uk/biostudies/studies/S-EPMC12915010biostudies-literatureUnknown24(1)Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic synovial inflammation, cartilage destruction, and bone loss. Current therapeutic approaches are often limited by short drug half-life, insufficient local drug release, and substantial systemic side effects.In this study, we developed a composite thermosensitive hydrogel system that integrates in situ gelation, sustained drug release, and multitarget therapeutic effects for localized precision treatment of RA.The system consists of a thermosensitive hydrogel matrix composed of hydroxypropyl methylcellulose (HPMC), hyaluronic acid (HA), and glycerol, in which gelatin methacryloyl (GelMA) hydrogel microspheres are embedded. The microspheres efficiently encapsulate Drynaria rhizome-derived extracellular vesicles (DR-EVJournal of nanobiotechnologyHydrogel microspheres loaded with sinomenine and Drynaria rhizome enhance the treatment of rheumatoid arthritis via immune regulation and promoting bone repair.PMC129150108237420682304928Li JZhang KZhao WGao JCai LLiu SZhou YXu SChen YZhu WChen SXiao BPei TfalseHydrogel microspheres loaded with sinomenine and Drynaria rhizome enhance the treatment of rheumatoid arthritis via immune regulation and promoting bone repair.Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic synovial inflammation, cartilage destruction, and bone loss. Current therapeutic approaches are often limited by short drug half-life, insufficient local drug release, and substantial systemic side effects.In this study, we developed a composite thermosensitive hydrogel system that integrates in situ gelation, sustained drug release, and multitarget therapeutic effects for localized precision treatment of RA.The system consists of a thermosensitive hydrogel matrix composed of hydroxypropyl methylcellulose (HPMC), hyaluronic acid (HA), and glycerol, in which gelatin methacryloyl (GelMA) hydrogel microspheres are embedded. The microspheres efficiently encapsulate Drynaria rhizome-derived extracellular vesicles (DR-EV2026-01-01T00:00:00Z2026 Jan2026-07-16T06:32:58.829Z2026-07-09T10:39:48.76ZS-EPMC129150104158215110.1186/s12951-026-04063-4