Ceria-Stabilized Zirconia/Alumina Nanocomposite (NANO-Zr) Surface Enhances Osteogenesis Through Regulation of Macrophage Polarization

Zirconia implants are recognized for their excellent biocompatibility, aesthetics, and favorable mechanical properties. However, the effects of zirconia surfaces on osteogenesis, particularly in the presence of macrophages, are still not well understood. This study compares two types of zirconia surfaces—ceria-stabilized zirconia/alumina nanocomposite (NANO-Zr) and 3 mol% yttria-stabilized tetragonal zirconia polycrystal (3Y-TZP)—with titanium (Ti) substrates. Both zirconia surfaces promoted macrophage adhesion and proliferation, facilitated a shift from M1 to M2 polarization, and created an immune microenvironment conducive to osteogenesis by downregulating IL-6 and TNF-α and upregulating IL-10 and TGF-β gene expression. In macrophage co-cultures, both zirconia surfaces also supported osteoblast adhesion and proliferation, with NANO-Zr notably enhancing osteogenic differentiation and mineralization. These results highlight NANO-Zr as a promising candidate for future dental and orthopedic implant applications.