A Sandwich-Like Coating for Dynamic Cerium Oxide Nanoparticles Delivery: Enhancing Osseointegration of Titanium...

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.