Dataset Information

Evaluation of longitudinal time-lapsed in vivo micro-CT for monitoring fracture healing in mouse femur defect models.

ABSTRACT: Longitudinal in vivo micro-computed tomography (micro-CT) is of interest to non-invasively capture the healing process of individual animals in preclinical fracture healing studies. However, it is not known whether longitudinal imaging itself has an impact on callus formation and remodeling. In this study, a scan group received weekly micro-CT measurements (week 0-6), whereas controls were only scanned post-operatively and at week 5 and 6. Registration of consecutive scans using a branching scheme (bridged vs. unbridged defect) combined with a two-threshold approach enabled assessment of localized bone turnover and mineralization kinetics relevant for monitoring callus remodeling. Weekly micro-CT application did not significantly change any of the assessed callus parameters in the defect and periosteal volumes. This was supported by histomorphometry showing only small amounts of cartilage residuals in both groups, indicating progression towards the end of the healing period. Also, immunohistochemical staining of Sclerostin, previously associated with mediating adverse radiation effects on bone, did not reveal differences between groups. The established longitudinal in vivo micro-CT-based approach allows monitoring of healing phases in mouse femur defect models without significant effects of anesthesia, handling and radiation on callus properties. Therefore, this study supports application of longitudinal in vivo micro-CT for healing-phase-specific monitoring of fracture repair in mice.

SUBMITTER: Wehrle E

PROVIDER: S-EPMC6877534 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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Evaluation of longitudinal time-lapsed in vivo micro-CT for monitoring fracture healing in mouse femur defect models.

Wehrle Esther E Tourolle Né Betts Duncan C DC Kuhn Gisela A GA Scheuren Ariane C AC Hofmann Sandra S Müller Ralph R

Scientific reports 20191125 1

Longitudinal in vivo micro-computed tomography (micro-CT) is of interest to non-invasively capture the healing process of individual animals in preclinical fracture healing studies. However, it is not known whether longitudinal imaging itself has an impact on callus formation and remodeling. In this study, a scan group received weekly micro-CT measurements (week 0-6), whereas controls were only scanned post-operatively and at week 5 and 6. Registration of consecutive scans using a branching sche ...[more]

PMID: 31768003

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Project description:The fracture hematoma that forms between the broken fragments of bone serves as a natural fibrin scaffold. However, there is no data regarding the differences between the micro-architectural and biological properties of hematomas formed in normally healing, delayed healing, and non-healing bone defects. Mimicking these three conditions in the rat femur, we demonstrate clear differences in fibrin clot morphology, which directly affect the gene expression pattern. Specifically, RNA-sequencing reveals that the expression of essential osteogenic genes in normally healing defects are significantly up-regulated, whereas in delayed and non-healing defects they are down-regulated. Surprisingly, there were no substantial differences between delayed and non-healing defects. Most importantly, this study demonstrates that the healing outcome has already been determined at the earliest stage of bone healing. These findings could be used to develop biomaterial scaffolds mimicking the micro-architectural properties of normally healing fracture hematoma as a treatment strategy for bone defects. The hypothesis of this study was that the micro-architectural properties of the initially formed hematoma has a significant effect on the regulation of the biological process at the fracture site, which ultimately determines the outcome of bone healing. Three different healing models were investigated - normally healing, delayed healing, and non-healing defects. The results demonstrated that the intrinsic micro-architectural properties of hematomas between those groups varied distinctly in terms of fiber diameter, porosity, and density of the formed fibrin network. Those differences influenced biological responses, as evidenced by a higher expression of osteogenic genes in normally healing compared to delayed and non-healing defects, and the failed activation of BMP-2 in non-healing defects. More importantly, our results demonstrate healing outcomes are already determined at the initial (hematoma) stage of bone healing.

Dataset Information

Evaluation of longitudinal time-lapsed in vivo micro-CT for monitoring fracture healing in mouse femur defect models.

Publications

Evaluation of longitudinal time-lapsed in vivo micro-CT for monitoring fracture healing in mouse femur defect models.

Similar Datasets

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