Cuttlefish ink nanoparticle-engineered hydrogel microspheres synergistically attenuate disc degeneration via antioxidant defense and matrix synthesis activation

Intervertebral disc degeneration (IVDD) is a leading cause of spinal disorders, affecting millions globally, particularly the aging population. Current treatments, however, fail to fully restore disc structure and function, highlighting the need for regenerative therapies. This study aims to construct an antioxidant artificial nucleus pulposus (NP) by incorporating cuttlefish ink nanoparticles (CINPs) into GelMA microspheres, thereby enhancing nucleus pulposus cell (NPC) viability and extracellular matrix (ECM) synthesis. Oxidative stress is a key driver of disc degeneration. CINPs, rich in proline and fucose, significantly enhanced the antioxidant capacity of NPCs, as evidenced by reduced intracellular reactive oxygen species (ROS) levels and activation of the nuclear factor erythroid 2-related factor 2/heme oxygenase-1 (NRF2/HO-1) pathway in our study. In vitro experiments demonstrated that GelMA@CINPs microspheres significantly enhanced NPC antioxidant capacity and promoted ECM secretion. Implantation of these microspheres into intervertebral discs (IVDs) of rats following discectomy validated their therapeutic efficacy in promoting NP tissue regeneration. In this experiment, the introduction of CINPs facilitates a dual antioxidant mechanism, comprising chemical (e.g., free radical scavenging by eumelanin via HAT/SET mechanisms) and biological (activation of the NRF2/HO-1 pathway) components. This synergistic approach directly addresses oxidative stress, a critical driver of intervertebral disc degeneration (IVDD) progression. This research introduces a novel strategy for improving cell-material interactions in tissue engineering, which enhances the potential for constructing an artificial NP and effectively treating IVDD.