Drilled hole defects in mouse femur as models of intramembranous cortical and cancellous bone regeneration.

In order to identify pertinent models of cortical and cancellous bone regeneration, we compared the kinetics and patterns of bone healing in mouse femur using two defect protocols. The first protocol consisted of a 0.9-mm-diameter through-and-through cortical hole drilled in the mid-diaphysis. The second protocol was a 0.9-mm-diameter, 1-mm-deep perforation in the distal epimetaphyseal region, which destroyed part of the growth plate and cancellous bone. Bone healing was analyzed by ex vivo micro-computerized X-ray tomography and histology. In the diaphysis, the cortical gap was bridged with woven bone within 2 weeks. This newly formed bone was rapidly remodeled into compact cortical bone, which showed characteristic parameters of intact cortex 4 weeks after surgery. In the epimetaphysis, bone formation was initiated at the deepest region of the defect and spread slowly toward the cortical gap. In this position, newly formed bone quickly adopted the characteristics of trabecular bone, whereas a thin compact wall was formed at its external border, which reached the density of intact cortical bone but failed to bridge the cortical gap even 13 weeks after surgery. This comparative study indicates that the diaphyseal defect is a model of cortical bone healing and that the epimetaphyseal defect is a model of cancellous bone repair. These models enable experimental genetics studies to investigate the cellular and molecular mechanisms of spontaneous cortical and cancellous bone repair and may be useful for pharmacological studies.