Cationic hydrogel with sustained lubrication and anti-calcification for osteoarthritis therapy

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.