Harnessing Anti-Inflammatory and Regenerative Potential: GelMA Hydrogel Loaded with IL-10 and Kartogenin for Intervertebral Disc Degeneration Therapy

Intervertebral disc degeneration (IVDD) is a major contributor to chronic back pain and disability, with limited effective therapeutic options. Current treatment options, including conservative management and surgical interventions, often fail to effectively halt disease progression and come with notable side effects. IVDD is characterized by the breakdown of the extracellular matrix (ECM) and the infiltration of inflammatory cells, which exacerbate disc degeneration. This study presents a novel therapeutic strategy aimed at addressing the dual challenges of inflammation and ECM degradation in IVDD. We developed a gelatin methacryloyl (GelMA) hydrogel system loaded with interleukin-10 (IL-10), an anti-inflammatory cytokine, and kartogenin (KGN), a small-molecule compound known for its regenerative properties. The KGN + IL-10@GelMA hydrogel was designed to deliver these agents in a controlled manner directly to the degenerated disc, targeting both the inflammatory microenvironment and the promotion of nucleus pulposus (NP) tissue regeneration. In a puncture-induced IVDD model, this hydrogel system effectively delayed the degenerative progression and facilitated NP regeneration. Our findings suggest that the KGN + IL-10@GelMA hydrogel holds significant potential as a nonsurgical treatment option for IVDD, offering a promising approach to mitigate the progression of IVDD and enhance disc repair.