Abstract

Zirconia implants offer excellent aesthetics and biocompatibility but are limited by intrinsic biocatalytic inertness, which impairs osseointegration and antimicrobial activity. Unlike existing zirconia surface modifications (e.g., passive micro/nano structuring or single-layer coatings) that lack time-controlled, multi-stage functionality. Here, we developed a dual-layer “sandwich” structure (Trbs-CeO 2 ) of cerium dioxide nanoparticles on the surface of zirconia by combining high-repetition-rate femtosecond laser physical modification with chemical modification using CeO 2 nanoparticles. The outer layer functions as a rapid-release layer, delivering high CeO 2 concentrations within hours to days post-implantation to emphasize anti-inflammatory and antibacterial effects; the inner layer is a slow-release layer characterized by a femtosecond laser-engineered micro-nano surface infused with CeO 2 , which continues to release low CeO 2 concentrations for several weeks after the outer layer is exhausted, thereby synergizing with the micro-nano structure of the zirconia substrate to enhance long-term osteogenesis. The anti-inflammatory, antibacterial, and osteogenic differentiation effects of Trbs-CeO 2 were evaluated in vitro , whereas its osteointegration capacity was evaluated in animal models. Compared with the control group, the Trbs-CeO 2 group exhibited significantly improved surface roughness, wettability, and biocompatibility of the zirconia surface. Trbs-CeO 2 exerts potent antibacterial activity by compromising bacterial cell membranes, induces M2 macrophage polarization, exhibits anti-inflammatory properties by inhibiting the TLR4/MyD88/NF-κB signaling pathway in RAW264.7 cells, and facilitates osteogenic MC3T3-E1 cell differentiation. Trbs-CeO 2 significantly enhances in vivo osseointegration efficiency. Trbs-CeO 2 provides a distinct, time-programmed dual-layer strategy that integrates antibacterial, anti-inflammatory, and osteogenesis-promotin