Light-crosslinked gelatin methacrylate hydrogel prevents intervertebral disc degeneration by delivering 10-hydroxy-2-decenoic acid to inhibit ferroptosis via NF-κB signaling.

Recurrence after discectomy and intervertebral disc degeneration (IDD) are common complications following surgery for lumbar disc herniation (LDH), and their pathological mechanisms are closely associated with iron-dependent cell death-ferroptosis. This study showed that the bioactive compound 10-hydroxy-2-decenoic acid (10-DHA), derived from royal jelly, can effectively inhibit ferroptosis in nucleus pulposus cells (NPCs) by NF-κB signaling, thereby restoring cellular homeostasis and reconstructing the integrity of the extracellular matrix (ECM). To further enhance therapeutic efficiency, we constructed the gelatin methacrylate (GelMA) hydrogel delivery system, achieving sustained release and precise localization of 10-DHA in IDD tissues. In preclinical models, 10-DHA@GelMA significantly suppressed ferroptosis in NPCs and promoted intervertebral disc (IVD) tissue regeneration. Experiments confirmed that it not only effectively prevents recurrence of LDH but also reverses the pathological progression of IDD. These findings demonstrate that 10-DHA, as a therapeutic candidate for ferroptosis-driven degenerative diseases, combined with a hydrogel-based targeted delivery strategy, provides an innovative intervention approach for clinical translation.