The regeneration of degenerated intervertebral discs viatissue engineering, biomaterials, and gene or cell-basedtherapies

Abstract Degenerative disc disease (DDD) remains one of the most prevalent and debilitating musculoskeletal disorders worldwide, with significant socioeconomic and quality-of-life implications. In the absence of a definitive cure, contemporary therapeutic strategies increasingly emphasize regenerative approaches aimed at restoring disc structure and function. Among these, tissue engineering, biomaterial scaffolds, and gene- or cell-based therapies represent the leading modalities under investigation. Each of these approaches offers distinct mechanisms and advantages: tissue engineering seeks to reconstruct the disc microenvironment through engineered constructs; biomaterials provide structural support and facilitate cellular integration; and gene or cell-based therapies target molecular pathways to modulate inflammation, promote matrix synthesis, and enhance endogenous repair. The selection of cell type, source, processing method, and delivery modality remains critical to optimizing therapeutic outcomes. This review explores the comparative benefits and limitations of these regenerative strategies, highlighting the need for an integrative and personalized approach to achieve durable and clinically meaningful restoration in patients with DDD.