Selenium-functionalized hydrogel microspheres promote nucleus pulposus reconstruction by activating selenoprotein-mediated mitochondrial redox homeostasis and energy metabolism.

Abstract

Degeneration of the nucleus pulposus (NP) is the primary contributor to lumbar intervertebral disc (IVD) disorders. While clinical discectomy is frequently employed to address advanced stages of IVD degeneration, this surgical intervention compromises the structural integrity of NP tissue, leading to a substantial decrease in the IVD's load-bearing capacity and hindering long-term pain relief. Selenoprotein is crucial in modulating mitochondrial redox homeostasis within NP cells, suggesting that selenium-based antioxidative stress therapy may be a promising approach for NP regeneration. In this study, we developed a selenium-functionalized hydrogel microsphere (SeNPs@GelMA) consisting of gelatin methacrylate (GelMA) and selenium nanoparticles (SeNPs). The SeNPs@GelMA microspheres serve as a vehicle for cell-based NP regeneration, supporting both cell delivery and antioxidative activity. In vitro experiments indicated that SeNPs@GelMA microspheres possess favorable cytocompatibility. Nucleus pulposus cells (NPCs) cultured on SeNPs@GelMA microspheres exhibited a marked enhancement in matrix synthesis, including aggrecan and type II collagen, alongside a significant suppression of matrix-degrading enzymes, even in an interleukin-1β-induced inflammatory environment. Notably, SeNPs@GelMA microspheres preserved mitochondrial redox homeostasis through the activation of glutathione peroxidase 1 (GPX1), thereby maintaining mitochondrial integrity and enhancing energy metabolism. When implanted into rat IVDs following discectomy, NPC-loaded SeNPs@GelMA microspheres facilitated NP regeneration and effectively restored biomechanical function, as evidenced by a substantial increase in IVD disc height and water content at the defect site. These findings indicate that the integration of SeNPs@GelMA microspheres with cell therapy constitutes a promising approach for NP regeneration, offering potential therapeutic benefits for patients undergoing discectomy.