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Developing effective tissue-engineered constructs for bone regeneration requires careful assessment of the in vivo bone response to novel biomaterials, scaffold architectures, and biologically augmented, tissue-engineered constructs. Both the implant material and scaffold architecture are known to significantly effect the local tissue response (
1
–
3
). Consequently, in characterizing the performance of new bone implants, it is prudent to establish material-dependent and scaffold-architecture-dependent bone-growth phenomena, in addition to the effect of biological augmentation, e.g., preseeded cells, growth factors, and cell-attachment proteins. Here we describe rabbit transcortical pin and trephine defect models, which, in combination, yield a method to investigate such variables on bone regeneration. The necessary histological and histomorphometry procedures are also detailed.