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Instruments / Technical Area	Publication Details	Published	Actions
I13-2-Diamond Manchester Imaging	Multiscale characterization of embryonic long bone mineralization in mice Isabella Silva Barreto , Sophie Le Cann , Saima Ahmed , Vivien Sotiriou , Mikael J. Turunen , Ulf Johansson , Angel Rodriguez-Fernandez , Tilman A. Grünewald , Marianne Liebi , Niamh C. Nowlan , Hanna Isaksson Advanced Science 143 DOI: 10.1002/advs.202002524 Diamond Proposal Number(s): [14789, 16557] Open Access Show Abstract ▼ Abstract: Long bone mineralization occurs through endochondral ossification, where a cartilage template mineralizes into bone‐like tissue with a hierarchical organization from the whole bone‐scale down to sub‐nano scale. Whereas this process has been extensively studied at the larger length scales, it remains unexplored at some of the smaller length scales. In this study, the changes in morphology, composition, and structure during embryonic mineralization of murine humeri are investigated using a range of high‐resolution synchrotron‐based imaging techniques at several length scales. With micro‐ and nanometer spatial resolution, the deposition of elements and the shaping of mineral platelets are followed. Rapid mineralization of the humeri occurs over approximately four days, where mineral to matrix ratio and calcium content in the most mineralized zone reach adult values shortly before birth. Interestingly, zinc is consistently found to be localized at the sites of ongoing new mineralization. The mineral platelets in the most recently mineralized regions are thicker, longer, narrower, and less aligned compared to those further into the mineralized region. In summary, this study demonstrates a specific spatial distribution of zinc, with highest concentration where new mineral is being deposited and that the newly formed mineral platelets undergo slight reshaping and reorganization during embryonic development.	Sep 2020
I13-2-Diamond Manchester Imaging	Muscular loading affects the 3D structure of both the mineralized rudiment and growth plate at early stages of bone formation Maria Pierantoni , Sophie Le Cann , Vivien Sotiriou , Saima Ahmed , Andrew J. Bodey , Iwan Jerjen , Niamh C. Nowlan , Hanna Isaksson Bone DOI: 10.1016/j.bone.2021.115849 Diamond Proposal Number(s): [14789, 16557] Open Access Show Abstract ▼ Abstract: Fetal immobilization affects skeletal development and can lead to severe malformations. Still, how mechanical load affects embryonic bone formation is not fully elucidated. This study combines mechanobiology, image analysis and developmental biology, to investigate the structural effects of muscular loading on embryonic long bones. We present a novel approach involving a semi-automatic workflow, to study the spatial and temporal evolutions of both hard and soft tissues in 3D without any contrast agent at micrometrical resolution. Using high-resolution phase-contrast-enhanced X-ray synchrotron microtomography, we compare the humeri of Splotch-delayed embryonic mice lacking skeletal muscles with healthy littermates. The effects of skeletal muscles on bone formation was studied from the first stages of mineral deposition (Theiler Stages 23 and 24) to just before birth (Theiler Stage 27). The results show that muscle activity affects both growth plate and mineralized regions, especially during early embryonic development. When skeletal muscles were absent, there was reduced mineralization, altered tuberosity size and location, and, at early embryonic stages, decreased chondrocyte density, size and elongation compared to littermate controls. The proposed workflow enhances our understanding of mechanobiology of early bone formation and could be implemented for the study of other complex biological tissues.	Jan 2021

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