Multifunctional mPDA@Mel-AB/BG hydrogels: Integrating ROS scavenging, inflammation suppression, and cartilage repair for osteoarthritis therapy.

Osteoarthritis (OA) is a multifactorial, chronic inflammatory joint disease marked by persistent inflammatory infiltration and oxidative stress. These pathological processes ultimately result in cartilage degradation and osteophyte formation. Therefore, the development of biomaterials capable of synergistically scavenging reactive oxygen species (ROS), suppressing inflammatory cytokine production, and facilitating cartilage regeneration represents a critical strategy for effectively treating OA. In this study, drug-loaded nanoparticles and bioactive glass were integrated into a natural polymer hydrogel composed of oxidized chondroitin sulfate (OCS) and carboxymethyl chitosan (CMC) to construct a new multifunctional injectable hydrogel. The hydrogel exhibited excellent mechanical strength and biocompatibility. Mesoporous dopamine nanoparticles (mPDA NPs) loaded with melatonin (Mel) and ammonia borane (AB) can achieve sustained release of Mel and AB after in situ injection, among which AB exhibits pH-responsive release characteristics in the microenvironment and produces a large amount of H2, thereby showing significant ROS scavenging ability and anti-inflammatory activity, effectively alleviating synovitis and cartilage matrix degradation. In addition, the hydrogel matrix synergizes with bioactive glass to promote the expression of cartilage-related synthetic proteins and exert cartilage repair function. The water retention and hygroscopicity of this multifunctional hydrogel help reduce intra-articular friction and inhibit osteophyte formation, thereby delaying the pathological progression of osteoarthritis. The aforementioned research findings indicate that the mPDA@Mel-AB OCS/CMC-BG hydrogel, as an intelligent biomaterial, holds significant potential for broad applications in the therapeutic strategy for osteoarthritis.