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 (HS), 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, 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.

中文翻译：

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通过自愈可注射水凝胶调节类风湿性关节炎微环境，以改善炎症消除和骨修复

类风湿性关节炎（RA）微环境往往会导致高度炎症、内源性气体水平失衡和治疗效果不佳的恶性循环。为了打破这个循环，我们开发了一种双气体介导的可注射水凝胶，用于调节 RA 的免疫微环境并同时释放治疗药物。水凝胶（DNRS凝胶）可以通过消耗过量的一氧化氮（NO）并释放治疗性硫化氢（HS）来按需分解，从而导致内源性气体恢复、炎症减轻和巨噬细胞极化为M2型。此外，水凝胶可以抑制破骨细胞生成并增强成骨作用。此外，关节内注射甲氨蝶呤水凝胶（MTX/DNRS凝胶）可显着减轻胶原诱导的关节炎大鼠模型中的炎症和临床症状，并促进骨侵蚀的修复。结果表明，MTX/DNRS凝胶恢复了微环境，提高了MTX的治疗效果。这项研究为开发用于 RA 治疗的多功能智能交付平台提供了新的理解。