Hydrogel delivery systems in intervertebral disc degeneration: Current status and future perspectives

Intervertebral disc degeneration (IVDD) is a primary contributor to the development of low back pain, characterized by core pathological features which include extracellular matrix (ECM) degradation, oxidative stress, imbalanced inflammatory microenvironment, and cellular functional exhaustion. Conventional therapies (e.g., pharmacological interventions and surgical treatments) face challenges in achieving functional regeneration of intervertebral discs. Hydrogel delivery systems, leveraging their unique "structure-function" dual advantage, have emerged as an ideal bridge linking palliative care to regenerative repair. This review systematically summarizes recent advances in hydrogel applications for IVDD treatment, guided by the "soil-seed" theory. We analyze three core strengths: 1) microenvironment-modulating hydrogels (e.g., pH/ROS-responsive materials, decellularized matrix hydrogels) for remodeling degenerative microenvironments; 2) cell delivery and protective hydrogels (cell-laden hydrogels, gene-activated hydrogels, exosome-encapsulated hydrogels) to enhance cellular survival and functionality; and 3) the integration of smart-responsive and multifunctional hydrogels for spatiotemporally precise therapy. We highlight breakthrough applications in anti-inflammatory drug delivery, ECM biomimetic repair, mechanical compatibility design, and multimodal synergistic therapy. Current challenges are critically examined, including mismatched degradation-regeneration cycles and the lack of standardized therapeutic evaluation systems. We also illustrate future directions, which envision interdisciplinary convergence (e.g., materials science, gene editing, artificial intelligence) to advance hydrogel systems toward intelligent and precise therapeutics, ultimately realizing a paradigm shift from structural repair to functional reconstruction in IVDD management.