Complexed Micelles System Based on Ceria Oxide Nanozyme for Bone Remodeling and ROS Scavenging in Periodontitis

Abstract Periodontitis is a chronic inflammatory disease caused by dental plaque and characterized by excessive accumulation of reactive oxygen species (ROS). Current treatments often fail to eliminate persistent inflammation and regenerate damaged tissue. Here, an ROS‐responsive multifunctional micelle system (HA‐PMs@Ce) constructed by self‐assembly of the block copolymer polyethylene glycol–polylysine/phenylboronic acid (PLLA‐ b ‐PLys/PBA) and tannic acid (TA) is proposed, encapsulating cerium oxide (CeOx) nanozyme and coated with hyaluronic acid (HA). The catechol groups in TA form ROS‐sensitive borate ester bonds with PBA, while electrostatic interactions between anionic HA and cationic PLys stabilize the micelle structure. In the oxidative microenvironment of periodontitis, excess ROS cleaves HA‐PMs@Ce, triggering the release of CeOx and TA on demand. CeOx mimics superoxide dismutase activity to scavenge ROS and alleviate oxidative stress, whereas TA provides antibacterial effects to prevent local infection. Furthermore, the micelle system reprograms M1 macrophages into the M2 phenotype, reduces pro‐inflammatory cytokines, and upregulates osteogenic gene expression, thereby attenuating inflammation and promoting tissue regeneration. Notably, HA‐PMs@Ce restores mitochondrial function and mitigates ROS‐induced damage. Overall, this nanozyme‐based micelle platform offers a promising strategy for the treatment of periodontitis.