Osteoarthritis‐Microenvironment‐Triggered Phase Alteration of Injectable Conductive Hydrogel for Attenuating Cartilage Degradation

Osteoarthritis (OA) is associated with excessive reactive oxygen species (ROS) production, which contributes substantially to chondrocyte dysfunction, oxidative stress, and cartilage degradation. Although stimuli-responsive hydrogels have emerged as promising platforms for OA therapy, conventional hydrogel-based systems exhibit limited sensitivity and require external detection equipment, highlighting the need for a simple, sensitive, and directly observable monitoring system. To address these challenges, we developed a ROS-triggered, in situ-forming gel-sol transition of a polydopamine (PDA)-loaded, diselenide-crosslinked polymer dot (PD) injectable hydrogel (HGC-PDA@PD or OA gel) as a monitorable theranostic for OA therapy at physiological temperature (37°C). The monitorable OA microenvironment-responsive hydrogel relied on interactions between the high ROS levels in OA cartilage and the OA gel, which triggered diselenide bond cleavage and the release of PDA from PD, causing a unique gel-sol transition of the OA gel. Owing to PDA release after diselenide breakage, the fluorescence and electroconductivity of the OA gel changed, which could serve as additional signals during OA detection. In vitro studies demonstrated the sensitive gel-sol transition of OA gel towards OA-induced immature articular chondrocytes (IL-1β/siSOD1/siCatalase-transfected iMACs). Furthermore, the OA gel showed a distinct gel-sol transition in cartilage of an in vivo OA mouse model compared with that in control mice. The lower transcription levels of cartilage matrix-degrading enzymes (ADAMTS4, ADAMTS5, MMP-3, and MMP-13) observed after OA gel injection confirmed that the OA gel could scavenge ROS and attenuate cartilage damage, revealing its potential application for dual-function OA diagnosis and rehabilitation.