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Additive manufacturing (AM) enables patient-specific lattice-based implants with porosity engineered to encourage bone ingrowth and to mimic bone's mechanical stiffness. The strength of the bone-implant interface can be measured through a destructive 'push-out' testing. The aim of this study is to explore the effect of implant-bone stiffness ratio (γ) on the push-out force using numerical simulation and a small experimental study. Numerical simulations of an implant-bone interface during a push-out test showed a fundamental change of failure mode for γ ranging from 0.1 to 10. For the geometry considered, the largest push-out forces were predicted for γ ≈ 0.7, essentially doubling the push-out force compared to a solid titanium implant. The experimental and simulation results also demonstrated that using an intermediate stiffness metal implant lattice geometry, γ ≈ 1.35, does not significantly improve the peak force of the push-out test compared to the solid implant. For the experimental study, critical-sized defects were simulated via robotic bone resection in the right lateral distal femur of a group of ~ 2.5-year-old healthy sheep, and then solid or lattice-based Ti6Al4V implants inserted. The femurs were harvested 6 months after implantation. Nine of the implanted femurs (six solid and three lattice-based) were used for fixation testing. The experimental study showed no significant difference in push-out force between a solid and moderately stiff lattice metal implant as indicated by the numerical simulation. [ABSTRACT FROM AUTHOR]