Microarc Oxidation Coatings Doped with a Low Proportion of Yttrium Enhance the Osseointegration of Titanium Implants through the BMP/Smad Pathway

Adding metal ions is a promising strategy to enhance the biological performance of titanium implants. In this study, we aimed to explore the effects of yttrium on the osseointegration of titanium implants. First, a series of yttrium-doped titanium surfaces were fabricated via microarc oxidation (MAO) by incorporating yttrium acetate into the electrolyte, and then the surface characteristics of different substrates were evaluated. Subsequently, the cellular behaviors of different coatings were assessed, and the osteointegration effects were examined using a rat model. Finally, high-throughput sequencing was employed to elucidate the underlying mechanisms of the yttrium-doped MAO coatings. As the results indicated, the proportion of yttrium in the coatings increased as the concentration of yttrium acetate improved. Surface characterization revealed that the yttrium-doped MAO coatings exhibited a homogeneous porous morphology, with comparable roughness and wettability to those of the undoped MAO coating, while the morphology became inconsistent when the yttrium acetate concentration reached 30 mM. The <i>in vitro</i> assays demonstrated that the addition of yttrium notably improved the cell adhesion, spreading, proliferation, and osteogenic differentiation of MAO coatings when doped with a low proportion, accompanied by enhanced osseointegration according to the <i>in vivo</i> experiments. Further exploration revealed a significant enrichment of osseointegration-related signaling factors and the activation of BMP/Smad signaling in the effects of yttrium-doped titanium coatings, which was attributed to the excessive accumulation of phosphorylated Smad1/5/9 in the nucleus. In summary, our work demonstrates that the use of MAO coatings doped with a low proportion of yttrium can enhance the osseointegration of titanium implants, providing an efficient strategy to optimize titanium implant performance.