Influence of scaffold micro architecture on bone regeneration: a multi-physics parametric study

The mechanical environment of a bone defect strongly influences tissue regeneration, and the geometry of a scaffold plays a key role in guiding this process. Triply periodic minimal surface (TPMS) structures have emerged as promising candidates for bone repair due to their connected porosity, predictable mechanical behaviour, ability to support cell transport, and manufacturability. In this study, we performed a parametric computational analysis to identify which geometric features of TPMS-based ceramic scaffolds most effectively promote bone regeneration without compromising mechanical performance. Four TPMS architectures were generated with different porosities and connectivity configurations, and their regenerative potential was assessed using a validated mechano-biological model of cell-driven bone formation. Mechanical stiffness, permeability, and morphometric properties were also quantified to evaluate how architectural parameters influence the scaffold's structural and biological behaviour. The results show that scaffold porosity and pore connectivity substantially affect cellular ingrowth, with highly porous and fully interconnected (Network-type) geometries promoting a 20-30% faster regeneration with respect to the Sheet-type. Among the designs studied, the Primitive architecture presented the fastest bone regeneration, while the Diamond architecture exhibited the most favorable balance between regenerative potential, surface area for cell adhesion, and mechanical compliance, whereas IWP structures provided high stiffness. Overall, this parametric analysis identifies the geometric features that most strongly enhance osteogenic performance, offering quantitative guidance for the design of TPMS ceramic scaffolds optimised for bone regeneration.