Characterization of a small animal growth plate injury model using microcomputed tomography

Abstract

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.