Computational Performance Evaluation of Porous Ti-6Al-4V Scaffold Architectures for Femoral Defect Healing Using a Coupled Finite Element-Mechanoregulation Framework.

Additively manufactured porous titanium scaffolds can provide fixation and guide regeneration of large bone defects, but design choices are constrained by uncertainty in how tissue formation and fatigue-driven failure co-evolve under rehabilitation loading. A patient-specific femoral diaphyseal defect was reconstructed and filled with Ti-6Al-4V scaffolds spanning 16 architectures across strut-based, sheet-based triply periodic minimal surface (TPMS), and stochastic families, all designed at 75% porosity with a 1 mm minimum feature thickness. A coupled finite element-mechanoregulation framework simulated 240 days of healing: finite-element fields drove a lattice-based mechanoregulation model using octahedral shear strain, while scaffold fatigue damage altered the evolving mechanical environment. Thirteen architectures preserved structural integrity under both conservative and aggressive rehabilitation protocols and converged to near-mature tissue densities (~1.90-1.91 g/cm3) with similar bridging patterns, indicating predicted osteogenic progression when mechanical stability was maintained. Failure was topology- and protocol-dependent: Lidinoid collapsed under both protocols, whereas Gyroid and SplitP failed only under aggressive loading, with fatigue damage localizing in the mid-defect region and propagating along continuous sheet connectivity. Among the surviving designs, Face-Centered Cubic, Simple Cubic, Octet, and Voronoi belonged to a favorable low-damage group; the sub-percent differences in terminal density did not resolve a unique biological optimum. Literature comparisons were used to contextualize the predicted healing trends. Overall, the framework provides a computational screening basis for identifying failure-prone architectures and prioritizing mechanically stable candidates for subsequent matched testing.