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Inspired by the impact of daily diet on RA, herein we proposed an innovative energy metabolism modulation strategy to reprogram synovial macrophages for RA treatment. An implantable hydrogel, encapsulating with optogenetics\u2010engineered cells, was designed to enable in\u2010situ and on\u2010demand secretion of glucagon\u2010like peptide\u20101 (GLP\u20101) through blue light irradiation. GLP\u20101 in synovium was found to activate GLP\u20101R\/HK2\/VDAC1 pathway to upregulate the tricarboxylic acid cycle and oxidative phosphorylation in macrophages. This metabolic reprogramming elicited a phenotypic transition in macrophage polarization, shifting from M0\/M1 state to M2 state. Significantly, the GLP\u20101\u2010mediated approach reduced synovial inflammatory cytokine levels and facilitated tissue repair and bone erosion recovery. These findings reveal the therapeutic potential of GLP\u20101R\/HK2\/VDAC1 pathway as a novel target for RA.<\/jats:p>","DOI":"10.1002\/advs.202523949","type":"journal-article","created":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T14:46:15Z","timestamp":1778597175000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["An Implantable Optogenetics\u2010Engineered Hydrogel for Amelioration of Rheumatoid Arthritis through Light\u2010Controlled Metabolic Reprogramming of Synovial Macrophages"],"prefix":"10.1002","volume":"13","author":[{"given":"Dahai","family":"Hu","sequence":"first","affiliation":[{"name":"Department of Sports Medicine, The First Affiliated Hospital, Guangdong Provincial Key Laboratory of Speed Capability, The Guangzhou Key Laboratory of Precision Orthopedics and Regenerative Medicine, School of Medicine Jinan University  Guangzhou P. R. 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