Decoupling pore size and porosity in Voronoi bone scaffolds: A multiphysics framework for early osteogenic evaluation

The irregular, trabecular-like morphology of Voronoi-tessellated scaffolds makes them attractive for bone tissue engineering. However, most existing Voronoi modelling methods cannot independently control pore size and porosity, restricting systematic evaluation of scaffold structure-function relationships. This study developed a discrete element method (DEM)-based Voronoi modelling framework that decouples pore size from porosity. A coupled multiphysics evaluation strategy was established, integrating static compression, computational fluid dynamics, discrete phase modelling, and mechano-regulation analysis. This framework assessed mechanical behaviour, mass transport, early MSC adhesion, and hematoma-stage osteogenic potential. Porosity primarily governed scaffold stiffness, whereas permeability was more sensitive to pore size. MSC adhesion was closely associated with specific surface area and was jointly regulated by transport accessibility and attachment area. Fluid shear stress contributed more to the composite mechanical stimulus than solid-phase strain across all scaffold designs, indicating that fluid-mediated stimulation dominated the local osteogenic microenvironment. The predicted mechano-regulated osteogenic potential was not maximized by any single structural parameter. Instead, it emerged from a balance between MSC capture efficiency and the adequacy of mechanical stimulation. These findings support a "capture-then-differentiate" mechanism for early osteogenesis in Voronoi scaffolds. The framework provides quantitative guidance for site-specific Voronoi scaffold design and a generalizable strategy for evaluating porous architectures from coupled biomechanical and biological perspectives.