Ti6Al4V scaffolds demonstrate significant translational potential for bone defect reconstruction, leveraging exceptional biocompatibility and corrosion resistance. However, achieving concurrent osseointegration enhancement and mechanical compatibility with native cancellous bone remains a critical design constraint. A trabecular bone-mimetic porous Ti6Al4V scaffold was fabricated via Voronoi-tessellated CAD and selective laser melting (SLM). Precise modulation of pore architecture enabled controlled porosity. Compression testing characterized the mechanical properties. Early-stage in vivo osseointegration was evaluated in a rabbit femoral condyle defect model using histomorphometry and micro-computed tomography (μCT) at 4/12 weeks, with comparative assessment against conventional Strut-based and G-curved lattices. The Voronoi scaffold exhibited cancellous bone-matching elastic modulus and yield strength, thereby mitigating stress-shielding effects. Biomechanics, CFD, and in vivo analysis demonstrated significantly enhanced osteogenic potential and superior bone-implant interface integration versus Strut and TPMS designs. The Voronoi design provides an effective biomimetic strategy for fabricating porous titanium alloy bone scaffolds with enhanced osteogenic properties. It has more potential than conventional struts and periodic TPMS structures in facilitating bone defect repair.