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Current treatments are limited in accessing a 3D platform that not only supports chondrocyte recovery and new cartilage matrix formation but also effectively modulates the inflammatory environment, particularly through macrophage regulation and extracellular vesicle (EV)\u2010mediated functions. Here, an injectable hydrogel is developed incorporating mannose oligosaccharide (MOS)\u2010modified chondroitin sulfate and hyaluronic. This hydrogel forms a porous structure in situ, supporting cell adhesion and matrix production. The MOS groups grafted onto the hydrogel bind to CD206 receptors of macrophages, selectively recruiting and regulating M2 macrophages over an extended period. These macrophages, in turn, release EVs with potent anti\u2010inflammatory properties, which support new cartilage formation and preservation. This innovative approach addresses a critical gap in RA treatment, offering a novel, cost\u2010effective, and efficient tissue\u2010engineering solution with the potential to significantly improve patient outcomes and quality of life.<\/jats:p>","DOI":"10.1002\/smtd.202500605","type":"journal-article","created":{"date-parts":[[2025,7,15]],"date-time":"2025-07-15T09:15:09Z","timestamp":1752570909000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Mannose Oligosaccharide\u2010Conjugated In Situ Pore\u2010Forming Injectable Hydrogels for Rheumatoid Arthritis Treatment by Reprogramming Macrophage Extracellular Vesicles"],"prefix":"10.1002","volume":"10","author":[{"given":"Anan","family":"Zhang","sequence":"first","affiliation":[{"name":"Basic Science Center Project of National Natural Science Foundation of China Frontiers Science Center for Materiobiology and Dynamic Chemistry Key Laboratory for Ultrafine Materials of Ministry of Education and School of Materials Science and Engineering East China University of Science and Technology  Shanghai 200237 P. 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