A Sandwich‐Like Coating for Dynamic Cerium Oxide Nanoparticles Delivery: Enhancing Osseointegration of Titanium Implants in Oxidative Microenvironment

Abstract Excessive reactive oxygen species (ROS) around titanium implants under pathological conditions can cause mitochondrial dysfunction, potentially resulting in implant failure or related complications. This study designs a titanium implant functionalized with cerium oxide nanoparticles (CeNPs) using phenylboronic acid‐modified hyaluronic acid (HA‐PBA) and carboxylated chitosan (CCS) as polyelectrolytes, with the primary objective of modulating the local microenvironment around the implant. Owing to the responsive properties of HA‐PBA, the embedded CeNPs are released in an on‐demand manner as the coating degrades under different conditions. The Ti‐HAPBA/CCS‐CeNPs implants not only directly stimulate osteoblast differentiation under physiological conditions but also mitigate oxidative stress‐induced mitochondrial dynamics imbalance and dysfunction. This protective effect is achieved by scavenging intracellular ROS, downregulating DRP1 expression, and restoring mitochondrial membrane potential (MMP). The osteoinductive efficacy of the Ti‐HAPBA/CCS‐CeNPs implants is further assessed using a femoral implantation model in diabetic rats, which demonstrates significantly enhanced bone remodeling and osseointegration at four and eight weeks post‐implantation compared to the Ti‐SLA group. Collectively, this study demonstrates the therapeutic potential of Ti‐HAPBA/CCS‐CeNPs implants under both physiological and pathological conditions, and provides a novel biopolymer‐based strategy for improving dental implant outcomes.