Large segmental bone defects represent a clinical challenge for which current treatment procedures have many drawbacks. 3D-printed scaffolds may help to support healing, but their design process relies mainly on trial and error due to a lack of understanding of which scaffold features support bone regeneration. The aim of this study was to investigate whether existing mechano-biological rules of bone regeneration can also explain scaffold-supported bone defect healing. In addition, we examined the distinct roles of bone grafting and scaffold structure on the regeneration process. To that end, scaffold-surface guided migration and tissue deposition as well as bone graft stimulatory effects were included in an in silico model and predictions were compared to in vivo data. We found graft osteoconductive properties and scaffold-surface guided extracellular matrix deposition to be essential features driving bone defect filling in a 3D-printed honeycomb titanium structure. This knowledge paves the way for the design of more effective 3D scaffold structures and their pre-clinical optimization, prior to their application in scaffold-based bone defect regeneration.
