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BACKGROUND: The practice of cement augmentation in pedicle screw fixation is well established. However, there is a lack of consensus regarding the optimal screw design or cement type. This remains a clinically important question given the incidence of cement augmentation-associated complications. While fenestrated screws have become widely used in clinical practice, the relationship between fenestration placement along the screw axis and cement plume geometry and pullout strength have yet to be clarified. This study was designed to evaluate the mechanical and geometric properties of different fenestrated screw designs and cement viscosities in pedicle screw fixation. METHODS: Three different screw fenestration configurations and 2 different cement viscosities were examined in this study. Axial pullout tests were conducted in both foam blocks and cadaveric vertebrae. All vertebral specimens underwent tests of bone mineral density. In the foam blocks, 6 tests were conducted for each augmentation combination and also for nonaugmented controls. In the cadaveric testing, 36 lumbar vertebrae were instrumented with a cemented and uncemented control screw to compare features of fixation. Computed tomography (CT) images were taken to assess the geometric profile of the cement plumes in both the foam blocks and the cadaveric vertebrae. RESULTS: In both foam blocks and vertebral specimens, cementation was shown to confer a significant increase in pullout strength. Significant correlations existed between the anterior-posterior and lateral cement plume diameters and pullout strength in cadaveric vertebra and foam blocks, respectively. Within instrumented vertebra, variables such as the width of the vertebral body and screw insertion were found to significantly correlate with enhanced fixation. CT analysis of the instrumented vertebra demonstrated that a centrally distributed pattern of fenestrations was found to result in a cement plume with consistently predictable distribution within the vertebral body, without evidence of leak. CONCLUSION: Cementation of fenestrated pedicle screws increases overall pullout forces; however, there is an unclear relationship between the geometric properties of the cement plume and the overall strength of the screw-bone interface. This study demonstrates that the plume diameter, vertebral body width, and angle of screw insertion are correlated with enhanced pullout strength. Furthermore, varying the fenestration design of injectable screws resulted in a set of predictable plume patterns, which may be associated with fewer complications. Further investigation is required to clarify the optimal geometric and biomechanical properties of injectable pedicle screws and their role in establishing the cement-bone interface. CLINICAL RELEVANCE: This study is relevant to currently practicing spinal surgeons and biomechanical engineers. LEVEL OF EVIDENCE: 5.