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In this study, hydroxyapatite was obtained by the sol-gel method, and zirconia/hydroxyapatite composites (YSZ/HAp) were produced with weight proportions of 95/5, 90/10, 85/15, and 80/20, respectively. The samples were characterized by X-ray diffraction (XRD), Archimedes' principle, Fourier-transform infrared spectroscopy (FT-IR), Vickers microhardness, scanning electron microscopy (SEM) and field emission scanning electron microscopy (FESEM). The calvarial critical-sized defect experimental model in rats was used to evaluate the biological interaction between YSZ/HAp scaffolds and bone tissue by Micro CT analysis. The XRD patterns of composites showed the major intensity of the zirconia phase and lower intensity of the hydroxyapatite phase, but the FT-IR analysis confirmed the presence of hydroxyapatite. Dense composite materials were verified by way of the Archimedes' principle, where the YSZ/HAp 85/15 sample had lower apparent porosity (0.60%) and water absorption (0.10%). Vickers microhardness showed that composite material hardness decreased with the increase of hydroxyapatite, varying from 1367.43 to 711.37 HV. SEM images were possible to quantify the crack sizes in the indentations and to identify the elements presents by EDS, while FESEM was applied to analyze the morphology of the powders and microstructure of the composites. Among the composite studied, YSZ/HAp 85/15 and YSZ/HAp 80/20 samples were the compositions that demonstrated the best mechanical behavior with a fracture toughness of 9.2 and 9.3 MPa m1/2, respectively. The YSZ/HAp scaffold showed an interaction with bone tissue. The percent bone volume (BV/TV, p < 0.001) and bone mineral density (BMD, p < 0.01) were significantly increased in Zirconia/hydroxyapatite scaffold. [ABSTRACT FROM AUTHOR]