Intervertebral disc degeneration (IVDD), primarily driven by oxidative stress and inflammation, significantly impacts patient quality of life. Current therapies lack efficacy, highlighting the need for novel treatment strategies. This study investigates the protective effect of antioxidant hydrogel microspheres containing black phosphorus (BP) nanosheets and extracellular vesicles (EVs), fabricated using a microfluidic technology-based delivery system, designated as EVs@BPMS. In vitro analyses of EVs@BPMS revealed that BP nanosheets enhanced the antioxidant capacity of the hydrogel microspheres. The EVs@BPMS system functioned through the sustained release of extracellular vesicles. These vesicles collectively mitigated oxidative damage by scavenging reactive oxygen species (ROS), reducing oxidative stress, suppressing cellular senescence, and ultimately restoring extracellular matrix homeostasis in nucleus pulposus cells. Transcriptomic analysis further elucidated that the microspheres inhibited inflammatory responses via the IL-17-ferroptosis pathway, providing a theoretical basis for the development of targeted therapeutic interventions. In vivo studies confirmed the protective efficacy of EVs@BPMS in a rat model of IVDD, demonstrating substantial attenuation of disc degeneration. The findings underscored the innovative capacity of antioxidant hydrogel microspheres in regulating oxidative stress and maintaining cellular homeostasis. Moreover, they highlighted the potential of these microspheres for clinical application in degenerative disc disease.
