CeO₂ Nanozyme-Engineered Dental Pulp Mesenchymal Stem Cells for Periodontal Regeneration

Periodontitis, a chronic inflammatory disease, leads to the progressive destruction of tooth-supporting tissues, and current treatments fall short of fully restoring periodontal regeneration. Dental pulp stem cells (DPSCs) have shown great promise for periodontal regeneration due to their ability to differentiate into multiple cell types and modulate immune responses. However, clinical use of DPSCs remains challenging due to poor cell retention, dependence on scaffolds, and high costs. Additionally, excessive reactive oxygen species (ROS) in the periodontal microenvironment hinder stem cell proliferation and differentiation, further limiting their regenerative potential. To address these challenges, we developed ultrafine cerium oxide nanoparticles (CeO2NPs) and engineered DPSCs (E-DPSCs) by incorporating these antioxidant nanozymes via endocytosis. The modified E-DPSCs exhibited enhanced proliferation, migration, and osteogenic differentiation under normal conditions. Crucially, under oxidative stress, E-DPSCs effectively neutralized ROS, reduced apoptosis, and maintained their osteogenic capacity. In vivo studies further demonstrated that E-DPSCs significantly enhanced periodontal regeneration compared to unmodified DPSCs. These findings highlight E-DPSCs as a promising solution to overcome current limitations in stem cell therapy, offering a more effective strategy for periodontal repair and regeneration.