Engineered Extracellular Vesicles for Intervertebral Disc Regeneration: Mechanisms, Strategies, and Translational Potential

Intervertebral disc degeneration (IVDD) is a primary contributor to chronic low back pain and disability, yet current treatment strategies remain largely palliative, with limited regenerative potential. Engineered extracellular vesicles (EVs) have emerged as a promising class of bio-nanocarriers, offering low immunogenicity, high biocompatibility, and precise therapeutic cargo delivery. This review systematically summarizes recent advancements in EV engineering approaches, including cargo loading techniques, surface functionalization, and integration with stimuli-responsive biomaterials, and delineates their mechanistic roles in modulating inflammation, cellular senescence, and extracellular matrix remodeling in the degenerated disc microenvironment. Furthermore, we structure the discussion around a "carrier-mechanism-application" axis, providing a conceptual and technical framework to guide the development of EV-based regenerative therapies. Finally, we address current translational challenges and propose future directions to bridge the gap between bench and bedside in the context of IVDD treatment.