Regenerative Strategies for Intervertebral Disc MicroenvironmentRemodeling: Mesenchymal Stem Cells, Extracellular Vesicles and Hydrogels

IVDD (intervertebral disc degeneration) is an important pathological basis for lumbar intervertebral disc protrusion, intervertebral source lumbar pain, and degenerative lumbar diseases. Current treatmentsmainly focus on decompression, pain relief, and stabilization, but they are unable to restore the cellular, matrix, andmechanical homeostasis of the degenerated intervertebral discs. MSC (mesenchymal stem cell) mainly exert paracrine, immunomodulatory, and limited chondrogenic differentiation effects, and are limited by acidification, lownutrition, abnormal loading, and local retention; EV (extracellular vesicle) have the potential for cell-free deliveryand engineering, but the issues of standardized preparation, potency evaluation, and continuous delivery need to beaddressed; hydrogels can provide a biomimetic support and spatial delivery platform, but they need to balance viscoelasticity, degradation, resistance to extrusion, and annulus fibrosus closure. The value of the composite systemlies in achieving anti-inflammatory protection, matrix reconstruction, and mechanical adaptation according to thedegeneration stage, rather than simple component stacking. This article focuses on the three pathological axes ofendplate-nutrition-metabolism, inflammation-immunity, ECM-cell fate-mechanics coupling, and reviews the rolesof MSC, MSC-derived EVs, and hydrogels in the remodeling of the intervertebral disc microenvironment.

CSTR: 32200.14.cjcb.2026.10.0008