Intense inflammatory responses and elevated levels of reactive oxygen species (ROS) extremely exacerbate the pathological process of spinal cord injury (SCI). Mesenchymal stem cell (MSC)-derived extracellular vesicles (EV) can mitigate SCI-related inflammation but their production yield remains limited. Alternatively, MSC-extruded nanovesicles (NV) inherit the therapeutic potential from MSCs and have a markedly higher yield than EV. In the present study, a bio-responsive scaffold system (RS+NV) was created for SCI treatment. NV was generated from human MSCs by physical extrusion and encapsulated in a ROS-responsive scaffold (RS). RS+NV efficiently scavenged environmental ROS and underwent degradation, thus facilitating the responsive release of NV. NV inhibited the pro-inflammatory phenotypic transformation, and reduced the secretion of TNF-α and IL-6 from lipopolysaccharide-stimulated BV2 cells, exhibiting comparable anti-inflammatory properties to EV. Additionally, NV posed a superior antioxidative effect than EV and could effectively alleviate the oxidative stress damage of H