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journal article·2026-05-12Open access

An Implantable Optogenetics‐Engineered Hydrogel for Amelioration of Rheumatoid Arthritis through Light‐Controlled Metabolic Reprogramming of Synovial Macrophages

Dahai Hu, Yaru Sun, Qi Lu, Yi Zhang, Jieruo Li, Huige Hou, Huajun Wang, Hui Tang, Yunsong Zhang, Xiaofei Zheng, Qingsong Mei

Advanced Science
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Abstract

ABSTRACT Rheumatoid arthritis (RA) has always been a therapeutic challenge in clinical due to the lack of effective drug treatments. 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‐engineered cells, was designed to enable in‐situ and on‐demand secretion of glucagon‐like peptide‐1 (GLP‐1) through blue light irradiation. GLP‐1 in synovium was found to activate GLP‐1R/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‐1‐mediated approach reduced synovial inflammatory cytokine levels and facilitated tissue repair and bone erosion recovery. These findings reveal the therapeutic potential of GLP‐1R/HK2/VDAC1 pathway as a novel target for RA.
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Research context

PolymersBiomaterials

OpenAlex topics: 3D Printing in Biomedical Research · Supramolecular Self-Assembly in Materials · Graphene and Nanomaterials Applications

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

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. China

Department of Medical Biochemistry and Molecular Biology, School of Medicine Jinan University Guangzhou Guangdong P. R. China

The Clinical Medicine Research Institute The First Affiliated Hospital of Jinan University Guangzhou P. R. China

The Clinical Medicine Research Institute The Fifth Affiliated Hospital of Jinan University Heyuan P. R. China

The Department of Plastic and Reconstructive Surgery, The Affiliated Guangdong Second Provincial General Hospital Jinan University Guangzhou P. R. China

Funding

National Natural Science Foundation of China · Basic and Applied Basic Research Foundation of Guangdong Province

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