Rat Calvarial Defect Models in Bone Regeneration Research: A Narrative Review of Critical Size and Micro-Computed...

The rat calvarial defect model supports the preclinical evaluation of bone-regenerative approaches relevant to craniofacial reconstruction, including recombinant human bone morphogenetic protein-2 (rhBMP-2) and bone substitutes. However, its invasive nature requires study-specific harm-benefit assessment and application of the 3Rs. This narrative review used a structured PubMed search to examine spontaneous healing in defects smaller than 5 mm and μCT outcome reporting in untreated or control defects. Twenty-four studies of sub-5 mm defects and 45 μCT studies were included. Complete spontaneous healing was not reported in the sub-5 mm studies; only two μCT studies reported regeneration of at least 50% according to their respective outcome measures. Healing generally increased with longer observation periods and smaller defects, although methodological heterogeneity limited comparisons. Inconsistent reporting of acquisition parameters, segmentation thresholds, regions of interest, and numerical outcomes restricted reproducibility and data reuse. Within this PubMed-indexed evidence base, the findings support 5 mm defects as a practical model of incomplete spontaneous healing and indicate that smaller defects also do not reliably heal completely within the observation periods studied. These findings do not directly establish clinical benefit. Future studies should justify the least burdensome model capable of answering the research question, implement replacement, reduction, and refinement, and report standardized bone volume fractions, relevant measures of defect bridging, reproducible imaging methods, and reusable numerical data.