A TEMPO-loaded DNA hydrogel enabling integrated early diagnosis and treatment of osteoarthritis.

Osteoarthritis (OA) is a chronic inflammatory disease characterized primarily by cartilage degradation. Current imaging techniques often detect OA only after irreversible cartilage damage has occurred, and no drugs are available to halt disease progression. Early diagnosis and intervention may serve as an effective strategy to delay OA advancement. In this study, we developed a multifunctional material TEMPO@DSH by encapsulating 2,2,6,6-tetramethylpiperidine 1-oxyl (TEMPO), a reactive oxygen species (ROS)-responsive antioxidant, within anti-inflammatory DNA supramolecular hydrogel (DSH). TEMPO@DSH mitigates oxidative stress-induced mitochondrial damage in chondrocytes and inhibits the NF-κB and mTOR pathways, thereby reducing chondrocyte senescence and exerting therapeutic effects against OA. Additionally, by taking advantage of the loss of paramagnetism of TEMPO after reacting with ROS, magnetic resonance imaging following intra-articular injection of TEMPO@DSH can reflect the local levels of ROS in the joint. Given that elevated ROS levels precede observable imaging changes in early-stage OA, this approach enables early diagnosis. Overall, TEMPO@DSH serves as an integrated platform for the early diagnosis and treatment of OA, potentially offering a novel strategy for effective disease management.