Abstract Background Osteoarthritis is characterized by cartilage degradation and abnormal subchondral bone remodeling, primarily due to disrupted lubrication–calcification coupling. Current treatments mainly relieve symptoms but lack effective strategies against calcification, and lubrication supplements offer only temporary relief. Here, we present a novel dual-functional cationic hydrogel designed to simultaneously enhance lubrication and inhibit pathological calcification, targeting the dysregulated lubrication–calcification interaction in OA. This approach offers a promising disease-modifying strategy for OA treatment. Results Formulated from alkylated modified chitosan (mCS) and lysine (Lys), the mCS/Lys hydrogel exhibits dual functionalities: inhibiting pathological calcification and enhancing joint lubrication. These effects are achieved through structural modifications that create a brush-like architecture, recruiting endogenous lubricating factors and calcification precursors due to its intrinsic surface activity. Compared to clinically utilized hyaluronic acid, mCS/Lys hydrogel demonstrates an extended duration of action and enhanced therapeutic efficacy. The intra-articular delivery of the hydrogel in a murine osteoarthritis model demonstrated that the mCS/Lys hydrogel effectively inhibits pathological calcification, alleviates pain, and promotes the repair of articular cartilage. Conclusions Overall, the mCS/Lys hydrogel offers a more holistic and enduring treatment approach by integrating sustained lubrication with anti-calcification features. Compared to traditional single-target methods, it indicates a promising, translatable solution. Graphical abstract
Sun et al. (Sun,) studied this question.