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Understanding how the material properties of bone tissue from the various forms of osteogenesis imperfecta (OI) differ will allow us to tailor treatment regimens for affected patients. To this end, we characterized the bone structure and material properties of two mouse models of OI, the osteogenesis imperfecta mouse (oim/oim) and fragilitas ossium (fro/fro), in which bone fragility is due to a genetic defect in collagen type I and a defect in osteoblast matrix mineralization, respectively. Bones from 3 to 6 month old animals were examined using Fourier transform infrared spectroscopic imaging (FTIRI), microcomputed tomography (micro-CT), histology, and biochemical analysis. The attributes of oim/oim bone tissue were relatively constant over time when compared to wild type animals. The mineral density in oim/oim cortices and trabecular bone was higher than wild type while the bones had thinner cortices and fewer trabeculae that were thinner and more widely spaced. The fro/fro animals exhibited osteopenic attributes at 3 months. However, by 6 months, their spectroscopic and geometric properties were similar to wild type animals. Despite the lack of a specific collagen defect in fro/fro mice, both fro/fro and oim/oim genotypes exhibited abnormal collagen crosslinking as determined by FTIRI at both time points. These results demonstrate that abnormal extracellular matrix assembly plays a role in the bone fragility in both of these models.

Injuries to the growth plate remain a significant clinical challenge. The need to better understand mechanisms of growth disruption following transphyseal injuries and evaluate new therapeutic approaches to growth restoration motivates development of a well characterized model of growth plate injury. The goals of this study were to develop a growth plate defect model in the rat and to use microcomputed tomography (micro-CT) imaging to detect and quantify associated changes in growth plate morphology and mineralization over time following injury and in response to treatment. Three-dimensional images of the growth plate were created from micro-CT scans and used to quantify the volume of mineralized tissue within the defect site. Growth plate thickness and volume as well as the degree of growth plate fusion were also measured from the reconstructed 3D images. Growth deficiency was then quantified as a function of time post-injury from whole limb micro-CT scans. Finally, this model was used to determine the ability of an injectable in situ gelling hydrogel to prevent formation of a bony bridge within the defect and the subsequent effect on limb length deficiency and changes to growth plate morphology. Growth plate injury resulted in significant shortening of the defect limb by day 28 and significant thinning and fusion of the surrounding growth plate up to day 112. Limb length reduction was correlated with changes in the growth plate volume and average thickness at day 56. Injection of an in situ gelling agarose into the defect resulted in a reduction of limb length discrepancy as well as a thicker growth plate on average compared to empty defect controls. These results establish a novel method of characterizing changes in whole bone and growth plate morphology due to a growth plate injury and indicate that treatment with agarose hydrogel reduces limb length discrepancy but is not sufficient to regenerate growth plate tissue or fully restore growth function.