ABSTRACT Osteoarthritis (OA) is a degenerative joint disease characterized by cartilage degradation, chronic inflammation, and subchondral bone remodeling. Conventional intra‐articular therapies provide limited relief and fail to address its multifactorial pathogenesis. Here, we present an injectable hydrogel microsphere platform that integrates antioxidative, anti‐inflammatory, and regenerative functions for localized OA management. Uniform (∼125 µm) chondroitin sulfate methacrylate (ChSMA)‐based microspheres are fabricated via microfluidic photocross‐linking. Manganese dioxide nanoparticles provided catalytic reactive oxygen species (ROS) scavenging, while dexamethasone sodium phosphate enabled sustained release, reducing TNF‐α and IL‐6 levels by ∼30%. Bone marrow mesenchymal stem cells (BMSCs) are co‐delivered to promote cartilage repair. In vitro, the microspheres reduce intracellular ROS, induce M2 macrophage polarization, and suppress inflammatory cytokines by 60–70%, with IL‐10 levels increased by ∼90%. 3D co‐culture supports chondrocyte/BMSC viability and matrix production. In vivo, intra‐articular injection in a rat OA model markedly reduces cartilage erosion, decreases osteophyte volume by 80%, and improves subchondral bone microarchitecture. Histological staining confirms matrix restoration and structural preservation, with Osteoarthritis Research Society International (OARSI) scores reduced by 88%. Collectively, this injectable hydrogel microsphere system offers a minimally invasive and integrated strategy, simultaneously delivering antioxidative, anti‐inflammatory, and regenerative effects for comprehensive OA management.
Feng et al. (Fri,) studied this question.