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Achieving natural tooth appearance with sufficient mechanical strength is one of the most challenging issues of computer-assisted design and computer-assisted manufacturing (CAD-CAM) materials. However, limited evidence is available regarding their optical and mechanical properties for proper and evidence-based material selection in clinical practice.The purpose of this in vitro study was to assess and compare the translucency and biaxial flexural strength of 5 monolithic CAD-CAM restorative materials.Disk-shaped specimens (n=30) of each material (Lava Ultimate [LU], Vita Enamic [VE], Vitablocs Mark II [VMII], Vita Suprinity [VS], and IPS e.max CAD [IPS]) with a diameter of 12 mm and a thickness of 1.2 ±0.05 mm were prepared. A spectrophotometer was used to measure the translucency parameter. The specimens were then subjected to a biaxial flexure test using 3 balls and loaded with a piston in a universal testing machine at a cross-head speed of 0.5 mm/min until failure occurred (International Organization for Standardization standard 6872). Weibull statistics were used to evaluate the characteristic strength and reliability of each material. Chemical compositions were analyzed using an energy dispersive spectrometer, and microstructural analysis was conducted using scanning electron microscopy. Data were analyzed using 1-way ANOVA and the Tukey honest significant difference test (α=.05).Significant differences were found among the materials concerning translucency and biaxial flexural strength (P<.05). The highest mean transparency value was obtained in the VS group, whereas the lowest mean value was obtained in the VE group. The VS group produced the highest mean biaxial flexural strength, followed by the IPS, LU, VE, and VMII groups.Based on the results of the present study, zirconia-reinforced glass-ceramic revealed higher mean translucency and biaxial flexural strength than resin nanoceramic, feldspathic ceramic, lithium disilicate ceramic, and dual-network ceramic.