The purpose of this in vitro study was to measure the vertical, positive-horizontal, and negative-horizontal misfit (VM, PHM, and NHM, respectively) of the zirconia three-element prosthetic framework, fabricated using different methods, and compare them with conventional fabrication methods (lost-wax casting). Furthermore, this study aimed to evaluate the influence of the misfit values on the biomechanical behavior of the 3-unit fixed prosthetic frameworks using three-dimensional finite element analysis (3D-FEA). Forty frameworks (n = 10) were fabricated as follow: G1, Cerec Bluecam; G2, iTero; G3, 3Series; and G4, conventional method. The samples were randomized to measure marginal misfit using a high-precision three-dimensional (3D)-optical microscope. The results were submitted to analysis of variance (ANOVA), with the significance level set at 5%. The mean VM values of each group were used in creating the models by 3D-FEA with the misfit found in optical microscopy. The programs used were the InVesalius, Rhinoceros, SolidWorks, FEMAP and NEiNastran. The von Mises map was plotted for each model. The G4 showed the lowest mean VM value (16.73 μm), followed by G3 (20.71 μm), G2 (21.01 μm), and G1 (41.77 μm) (p < 0.001). G2 was more accurate than G1 (p < 0.05) and similar to G3 (p = 0.319). For PHM, G4 was the most accurate and did not present overextended values. With regard to NHM, the computer-aided design and computer-aided manufacturing (CAD-CAM) systems were more accurate (−61.91 μm) than G4 (−95.36 μm) (p = 0.014). In biomechanical analysis, stress concentration caused by oblique loading is greater than caused by axial loading. In axial loading, G4 was the most favorable while G1 was the least favorable, biomechanically, in oblique loading, similar stress patterns were observed in all the models. The prosthetic screw was the most overloaded structure, but the material did not influence the stress distribution. The misfit prostheses showed a greater degree of stress than the controls (without misfit). The manufacturing method influenced the marginal misfit of the frameworks, with the conventional method being the most accurate and the Cerec Bluecam System (closed system) the least accurate. Biomechanically, fitting prostheses were more favorable than misfit prostheses.
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