Regulation of rheumatoid arthritis microenvironment <i>via</i> a self-healing injectable hydrogel for improved inflammation elimination and bone repair.

Geng, Wenbo; Zhao, Jie; Tao, Bailong; Yang, Yulu; Duan, Qiaojian; Gao, Pengfei; He, Tingting; Liu, Shaopeng et al. · Bioact Mater · 2024

basic_science · Level V

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Abstract

The rheumatoid arthritis (RA) microenvironment is often followed by a vicious circle of high inflammation, endogenous gas levels imbalance, and poor treatment. To break the circle, we develop a dual-gas-mediated injectable hydrogel for modulating the immune microenvironment of RA and simultaneously releasing therapeutic drugs. The hydrogel (DNRS gel) could be broken down on-demand by consuming excessive nitric oxide (NO) and releasing therapeutic hydrogen sulfide (H<sub>2</sub>S), resulting in endogenous gas restoration, inflammation alleviation, and macrophage polarization to M2 type. Additionally, the hydrogel could suppress osteoclastogenesis and enhance osteogenesis. Furthermore, the intra-articularly injected hydrogel with methotrexate (MTX/DNRS gel) significantly alleviated inflammation and clinical symptoms and promoted the repair of bone erosion in the collagen-induced arthritis rat model. As a result, <i>in vivo</i> results demonstrated that MTX/DNRS gel restored the microenvironment and improved the therapeutic effect of MTX. This study provides a novel understanding of developing versatile smart delivery platforms for RA treatment.