Decoupling Pore Size and Porosity in Sheet-Based TPMS Scaffolds: Assessing Early Osteogenesis via a Capture-Then-Differentiate Framework.

Triply periodic minimal surface (TPMS) scaffolds possess significant application potential in bone tissue engineering owing to their smooth and continuous surface morphology and highly interconnected pore networks. However, in conventional parametric modeling of TPMS scaffolds, porosity and pore size usually vary in a coupled manner, restricting the systematic evaluation of scaffold structure-function relationships. In this study, a decoupled single-variable design strategy was adopted to construct homogeneous sheet-based TPMS scaffolds, including diamond sheet (DS), gyroid sheet (GS), and primitive sheet (PS) topologies, with independently controlled porosities (50%-90%) and pore sizes (500-900 μm). A sequential multiphysics framework integrating static compression finite element analysis (FEA), computational fluid dynamics (CFD), the discrete phase model (DPM), and mechano-regulation analysis was established to evaluate osteogenic potential during the early post-implantation hematoma stage. Results demonstrated that porosity primarily governed apparent stiffness, while permeability was highly sensitive to topological changes and pore size enlargement. The initial capture efficiency of mesenchymal stem cells (MSCs) was closely associated with the specific surface area (SSA) and dynamically regulated by flow trajectories and wall accessibility. Furthermore, mechano-regulation stimulus factor analysis, combining wall shear stress (WSS) and octahedral shear strain (OSS), revealed that WSS contributed dominantly to the local osteogenic microenvironment. Osteogenic differentiation efficiency was not maximized by any single structural parameter, but rather emerged from an optimal balance between the capacity to capture MSCs and adequate mechanical stimulation. These findings validate a "capture-then-differentiate" mechanism for early osteogenesis in sheet-based TPMS scaffolds, providing a quantitative multiphysics strategy for the topological optimization of bone scaffolds.