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Here, D\u2010mannose we identify as a potent immunometabolic modulator that enhances BMSC\u2010mediated osteochondral repair. Through in vitro experiments, we determined the optimal concentration of D\u2010mannose and evaluated its ability to preserve the osteogenic and chondrogenic differentiation potential of BMSCs under inflammatory microenvironment. Transcriptomic analysis demonstrated that D\u2010mannose contributed to the amelioration of inflammation by downregulating the NLRP3 inflammasome pathway. The metabolomic analysis further revealed that D\u2010mannose treatment alleviated inflammation\u2010induced dysregulation of the tricarboxylic acid cycle and facilitated the maintenance of glycolytic metabolic state in BMSCs. Furthermore, we fabricated a multifunctional GelMA\u2010based hydrogel incorporating D\u2010mannose (DM@GelMA). Macroscopic observation, micro\u2010CT analysis and histological evaluation confirmed that DM@GelMA hydrogel effectively promoted osteochondral tissue remodeling and integration in the OCD model of rats. These findings suggested that the multifunctional D\u2010mannose\u2010loaded composite hydrogel is a promising biomaterial for enhanced osteochondral regeneration.<\/jats:p>","DOI":"10.1002\/adhm.202503687","type":"journal-article","created":{"date-parts":[[2025,11,22]],"date-time":"2025-11-22T08:54:10Z","timestamp":1763801650000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Regulation of Inflammatory and Metabolic Microenvironment With a D\u2010Mannose Functionalized Hydrogel for Improved Osteochondral Regeneration"],"prefix":"10.1002","volume":"15","author":[{"given":"Wenhui","family":"Hu","sequence":"first","affiliation":[{"name":"Department of Orthopedics Nanjing First Hospital Nanjing Medical University  Nanjing Jiangsu China"},{"name":"Key Lab of Additive Manufacturing Technology Institute of Digital Medicine Nanjing Medical University  Nanjing Jiangsu China"},{"name":"Cartilage Regeneration Center Nanjing 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