Long-Term In Situ Treatment of Arthritis with Injectable Biocompatible Organogel Activation

Rheumatoid arthritis (RA), an autoimmune disease, severely impairs joint function and mobility, causing pain, stiffness, and joint deformity. As an active ingredient of ancient herbs and a widely studied polyphenol flavonoid glycoside, quercetin has a historical use in the treatment of rheumatoid arthritis. However, its low oral bioavailability and potential carcinogenic effects limit its systemic use. Therefore, we propose an injectable hydrogel-based targeted drug delivery system designed to respond to the pathological environment of rheumatoid arthritis joints. This system controls the release of anti-inflammatory drugs to promote joint repair. Low-temperature atmospheric plasma (LTAP), characterized by high-energy properties, activates the bioactivity of natural polyphenols. Utilizing LTAP to stimulate quercetin into protocatechuic acid, we prepared an efficacious gel system by dynamically coupling with poloxamer and sodium alginate. This organic gel maintains typical hydrogel properties of viscosity, biosafety, and temperature sensitivity. Compared with quercetin alone, this activated organic gel offers enhanced safety, absorption, and metabolism. In vivo studies have demonstrated that local injection of this hydrogel effectively reduces bone destruction, inhibits pannus formation, and significantly suppresses inflammatory factors such as IL-6, IL-1β, and TNF-α, thereby protecting joints. © 2025 The Authors. Published by American Chemical Society