Multiscale, interspecies evaluation of parameters affecting alveolar bone repair.

Abstract

BACKGROUND We undertook a comparative analysis of bone healing in the craniomaxillofacial (CMF) skeleton, focusing on the extent to which the physiological processes of bone repair and remodeling differed between different species. Understanding these differences can enhance the value of research outputs and thus improve treatment strategies. METHODS An osteotomy was produced in an equivalent anatomical location in mice, rats, minipigs, and human patients. Quantitative analyses were performed using micro-computed tomographic (µCT) imaging, histology, dynamic histomorphometry, immunohistochemistry, and cellular activity assays. RESULTS Non-invasive imaging analyses, histomorphometry, and molecular and cellular analyses together demonstrated that the overall bone repair program was highly conserved between rodents and minipigs, correlating with limited human data. Comparing the rate of bone repair across species was confounded by limited time points for analysis in human tissues. However, at later time points, CMF bone repair in minipigs was equivalent to CMF bone repair in rodents. CONCLUSIONS The molecular and cellular features of bone repair are shared among large and small animals, suggesting a common bone healing mechanism among species. Combined with the availability of transgenic lines and an extensive array of molecular and cellular analyses, this makes rodents an appealing choice for preclinical testing. PLAIN LANGUAGE SUMMARY We conducted this study to understand how bone heals in the head skeleton. We compared this repair process in animal models, including mice, rats, and minipigs, against a limited set of data from humans. Our goal was to determine whether bone repair and remodeling were conserved between species because this would have implications for preclinical studies to improve treatment strategies. We created a controlled injury in similar bone areas in each species, then examined the healing process using various research techniques, analyzing bone architecture and cellular activity. Our findings showed that the overall process of bone healing was similar between species. Although we had limited data from humans at later stages of healing, the healing patterns in minipigs closely matched those in rodents at the later stages. These similarities suggest that the way bones heal is equivalent among mammals. Therefore, with the added advantage of advanced research techniques available, rodents are an excellent choice for testing new treatments before advancing to studies in large animals and testing in humans.