A KAIST research team has developed a dual-functional hydrogel for rheumatoid arthritis that combines joint lubrication with immune regulation. The hydrogel is injectable, functions as a bio-lubricant, and alleviates immune cell–driven joint inflammation, thereby targeting key pathological features of rheumatoid arthritis.

Schematic illustration of an injectable hydrogel designed to treat rheumatoid arthritis by combining joint lubrication with immune regulation. The hydrogel helps calm overactive immune cells inside the joint, creating an anti-inflammatory environment that protects cartilage and reduces joint damage.

Rheumatoid arthritis (RA) is a chronic autoimmune disease in which the body’s immune system mistakenly attacks the joints. This leads to persistent inflammation, cartilage damage, bone erosion, and long-term pain. Although many treatments are available, most rely on broadly suppressing the immune system. While effective in some patients, these therapies often cause serious side effects and do not provide long-lasting relief due to poor drug retention in the affected areas.

A research team at KAIST, led by Dr. Woojin Back and Professor Ji-Ho Park, has developed a new material-based approach designed to treat rheumatoid arthritis locally, directly inside the joint. Acting as a joint lubricant while providing sustained immune regulation, the therapy works where inflammation actually occurs rather than circulating throughout the entire body.

The key innovation is an injectable hydrogel made from hyaluronic acid, a substance already widely used in joint injections. This hydrogel is engineered to withstand the repeated mechanical stress experienced in moving joints, similar to how natural joint fluid provides lubrication. However, the material does more than reduce friction. It also actively regulates immune responses inside the joint.

The hydrogel is chemically tethered with interleukin-4 (IL-4), a naturally occurring anti-inflammatory signaling protein. To function as a joint lubricant, the hydrogel must maintain specific mechanical properties, which makes conventional physical trapping of therapeutic proteins impractical due to rapid burst release. To overcome this fundamental limitation, the researchers chemically tethered interleukin-4 directly to the hydrogel network—an unprecedented strategy that enables sustained immune modulation while preserving the material’s lubricating function. This design allows the anti-inflammatory signal to remain active over time, while circumventing the systemic side effects that limit conventional therapies.

Inside inflamed joints, immune cells called macrophages play a central role in driving disease progression. In rheumatoid arthritis, these cells often remain in an aggressive, inflammatory state. The developed hydrogel was shown to shift these cells toward a calmer, tissue-repairing state, creating a more balanced immune environment. Laboratory studies confirmed that immune cells exposed to the developed hydrogel produced fewer inflammatory signals and more protective ones.

The therapeutic effect was further demonstrated in a mouse model of rheumatoid arthritis. Animals treated with the interleukin-4-tethered hydrogel showed reduced joint swelling, better preservation of cartilage, and less bone damage compared to untreated animals or those receiving the anti-inflammatory protein alone. Imaging and tissue analyses consistently indicated improved joint health.

This work highlights the potential of combining mechanical design with immune modulation. By functioning both as a joint lubricant and an immune-regulating platform, the hydrogel addresses two key aspects of rheumatoid arthritis simultaneously. Importantly, the platform is inherently customizable: by simply exchanging the therapeutic protein, it offers a future-ready strategy for treating a broad range of autoimmune diseases and cancer.

This study was conducted by Dr. Woojin Back as the first author, with Professor Ji-Ho Park serving as the corresponding author in the Department of Bio and Brain Engineering at KAIST. The research was published in Advanced Healthcare Materials under the title “Immunosuppressive Cytokine-Tethered Hydrogel for Treating Rheumatoid Arthritis” on May 26, 2025.

*DOI: 10.1002/adhm.202501613