From molecular regulation to tissue repair: hydrogels in the fight against intervertebral disc degeneration

Intervertebral disc degeneration (IVDD) is a leading cause of low back pain and involves multiple pathological processes, including cell apoptosis, senescence, oxidative stress-inflammation imbalance, and extracellular matrix (ECM) metabolic disorders. Current treatments such as pharmacotherapy, physical therapy, and surgery primarily relieve symptoms but fail to reverse the degenerative process and often carry the risk of complications.

This review systematically summarizes recent advances in the functional design and therapeutic applications of hydrogels for IVDD, with a focus on delivery systems, microenvironment modulation, and stimulus-responsive mechanisms. In vivo studies and preliminary clinical findings are also reviewed.

Hydrogels have emerged as a promising strategy for IVDD regenerative therapy due to their excellent biocompatibility, injectability, and dynamic responsiveness. Acting as multifunctional platforms, hydrogels can precisely deliver stem cells, exosomes, and nucleic acid drugs, regulate apoptotic pathways (e.g. Bax/Bcl-2, Caspase-3), suppress pro-inflammatory cytokines (e.g. TNF-α, IL-1β), and promote ECM synthesis (e.g. collagen II and proteoglycans). Additionally, the incorporation of antioxidant nanoparticles and stimuli-responsive systems allows for effective remodeling of the degenerative microenvironment and interruption of the oxidative stress-inflammation feedback loop. Hydrogels fabricated using 3D bioprinting techniques with biomimetic architectures further improve mechanical stability, preserve disc height, and delay progression of degeneration. Preliminary clinical studies have confirmed the safety and therapeutic potential of hydrogels in IVDD treatment.

Hydrogels demonstrate a multidimensional therapeutic potential ranging from molecular regulation to tissue repair. They hold great promise as a regenerative medicine strategy for precise and effective treatment of IVDD.