ROS-scavenging microspheres loaded with electromagnetically enhanced small extracellular vesicles for advanced osteoarthritis therapy

Osteoarthritis (OA) is a debilitating joint disease affecting over 240 million individuals globally, characterized by progressive cartilage degeneration and chronic inflammation. Despite its prevalence, treatment options remain limited and fail to prevent disease progression. In this study, we developed an innovative therapeutic strategy combining electromagnetic field-stimulated mesenchymal stem cell-derived small extracellular vesicles (EMF-sEV) with antioxidant gelatin methacryloyl (GelMA) hydrogel microspheres incorporating fullerenol nanoparticles (FMS). EMF stimulation significantly enhanced the yield and therapeutic potential of sEV, improving their ability to restore matrix homeostasis and suppress inflammation in OA chondrocytes. The EMF-sEV@FMS system demonstrated sustained release of EMF-sEV for up to 14 days, effectively reducing reactive oxygen species (ROS), mitigating oxidative stress, inhibiting apoptosis, and promoting chondrocyte proliferation in vitro . In a rat OA model, EMF-sEV@FMS alleviated cartilage degeneration and reduced osteophyte formation. Histological and immunohistochemical analyses confirmed the system's biocompatibility, anti-inflammatory properties, and therapeutic efficacy. These findings underscore the potential of EMF-sEV@FMS as a robust platform for OA treatment, combining targeted antioxidative effects with enhanced chondroprotective benefits. This work establishes a promising foundation for integrating sEV-based therapies with functional biomaterials to address complex joint diseases. Electromagnetic field-stimulated mesenchymal stem cell-derived small extracellular vesicles (EMF-sEV) delivered via fullerenol nanoparticle-incorporated GelMA hydrogel microspheres for osteoarthritis (OA) treatment. Mesenchymal stem cells (MSCs) were pre-treated with an electromagnetic field (EMF) to stimulate the production of sEV, which were subsequently harvested. EMF-sEV and fullerenol nanoparticles were co-encapsulated into GelMA hydrogel microspheres using microfluidic technology. Upon release, EMF-sEV and fullerenol nanoparticles acted synergistically to reduce reactive oxygen species (ROS) levels, thereby protecting chondrocytes and mitigating OA progression. • Antioxidant GelMA microspheres with EMF-enhanced sEVs (EMF-sEV@FMS) engineered for osteoarthritis therapy. • EMF stimulation amplified MSC-sEV yield, boosting anti-inflammatory and regenerative performance. • EMF-sEV@FMS sustained sEV release for 14 days and exhibited excellent biocompatibility. • EMF-sEV@FMS preserved cartilage integrity, suppressed inflammation, and restored joint homeostasis.