Morphology-Engineered Ceria Nanoparticles Ameliorate Periodontitis via Enhanced Antioxidant and Anti-Inflammatory Activities.

Periodontitis is a chronic inflammatory oral disease featured with continuous alveolar bone resorption, where a ccumulated reactive oxygen species (ROS) aggravate tissue damage and local inflammation. Ceria nanoparticles (CNPs) act as promising redox nanozymes with excellent ROS-scavenging and anti-inflammatory capacities. Their catalytic performance is highly dependent on specific surface area (SSA), surface Ce3+ fraction and oxygen vacancy (Ov) concentration, all of which are closely regulated by particle morphology. Nevertheless, the correlation between CNP morphology and therapeutic efficacy against periodontitis remains largely unexplored, hindering their rational application in oral therapy. Herein, ceria nanorods, nanocubes and nano-octahedra were synthesized via a hydrothermal method using the same precipitant, with commercial spherical CNPs serving as the control group. Ceria nanorods exerted superior enzyme-mimetic activity, ROS scavenging, anti-inflammatory and osteogenic effects in vitro, which is attributed to their largest SSA, highest surface Ce3+ proportion and abundant oxygen vacancies. In a rat periodontitis model, nanorod-loaded poloxamer hydrogel effectively alleviated alveolar bone resorption, clinical attachment loss and inflammatory infiltration. Mechanistic investigations demonstrated that nanorods inhibit the NF-κB signaling pathway while activating the Nrf2 pathway, thereby mitigating inflammation and reinforcing endogenous antioxidant defenses. This work clarifies the structure-activity relationship of CNPs, offering a rational morphology-modulating strategy for periodontitis therapy.