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A patient\u2010specific femoral diaphyseal defect was reconstructed and filled with Ti\u20106Al\u20104V scaffolds spanning 16 architectures across strut\u2010based, sheet\u2010based triply periodic minimal surface (TPMS), and stochastic families, all designed at 75% porosity with a 1\u2009mm minimum feature thickness. A coupled finite element\u2013mechanoregulation framework simulated 240\u2009days of healing: finite\u2010element fields drove a lattice\u2010based 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\u2010mature tissue densities (~1.90\u20131.91\u2009g\/cm\n                    <jats:sup>3<\/jats:sup>\n                    ) with similar bridging patterns, indicating predicted osteogenic progression when mechanical stability was maintained. Failure was topology\u2010 and protocol\u2010dependent: Lidinoid collapsed under both protocols, whereas Gyroid and SplitP failed only under aggressive loading, with fatigue damage localizing in the mid\u2010defect region and propagating along continuous sheet connectivity. Among the surviving designs, Face\u2010Centered Cubic, Simple Cubic, Octet, and Voronoi belonged to a favorable low\u2010damage group; the sub\u2010percent 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\u2010prone architectures and prioritizing mechanically stable candidates for subsequent matched testing.\n                  <\/jats:p>","DOI":"10.1002\/jbm.b.70165","type":"journal-article","created":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T06:08:13Z","timestamp":1792562893000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Computational Performance Evaluation of Porous Ti\u2010\n                    <scp>6Al<\/scp>\n                    \u2010\n                    <scp>4V<\/scp>\n                    Scaffold Architectures for Femoral Defect Healing Using a Coupled Finite Element\u2013Mechanoregulation Framework"],"prefix":"10.1002","volume":"114","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-5694-5336","authenticated-orcid":false,"given":"Panagiotis","family":"Ntakos","sequence":"first","affiliation":[{"name":"Laboratory of Machine Design National Technical University of Athens  Zografou Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6594-385X","authenticated-orcid":false,"given":"Christos","family":"Kalligeros","sequence":"additional","affiliation":[{"name":"Laboratory of Machine Design National Technical University of Athens  Zografou Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Athanasios F.","family":"Foukas","sequence":"additional","affiliation":[{"name":"Third Department of Orthopaedic Surgery \u201cKAT\u201d General Hospital of Athens  Kifissia 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