Imaging techniques for quantifying changes in the hierarchical structure of deforming joints are constrained by destructive sample treatments, sample-size restrictions and lengthy scan times. Here, we report the use of fast low-dose pink-beam synchrotron X-ray tomography in combination with mechanical loading at nanometric precision for in situ imaging, at resolutions below 100 nm, of the mechanical strain in intact untreated joints under physiologically realistic conditions. We show that in young, older and osteoarthritic mice, hierarchical changes in tissue structure and mechanical behaviour can be simultaneously visualized, and that the tissue structure at the cellular level correlates with the mechanical performance of the whole joint. We also use the tomographic approach to study the colocalization of tissue strains to specific chondrocyte lacunar organizations within intact loaded joints and to explore the role of calcified-cartilage stiffness on the biomechanics of healthy and pathological joints.
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Representative samples of research data from the experiments and of the data for the figures in the manuscript are provided in the Supplementary Information. The full data, of considerable size, are available from the corresponding authors on reasonable request.
The custom DVC code used in this study is available at https://zenodo.org/record/3228175#.XZdBRkZKguE.
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We are grateful to R. Mason (Imperial College London) for providing our original STR/Ort mice and for advice on their use. We thank L. Courtois, S. V. Boxel, C. Disney, G. Poologasundarampillai, J. He, D. Eastwood, K. Wanelik, U. Wagner and J. Thompson for their help during the beamtimes. We acknowledge the Engineering and Physical Sciences Research Council (grants EP/I02249X/1 and EP/M009688/1), Arthritis Research UK (grant 18768) and the MRC (grant MR/R025673/1). Facilities and research support were provided by the Diamond-Manchester Branchline (I13-2) at Diamond Light Source (Beamtimes MT13237-1, MT11076-1 and MT5003-1) and the Research Complex at Harwell.
The authors declare no competing interests.
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Madi, K., Staines, K.A., Bay, B.K. et al. In situ characterization of nanoscale strains in loaded whole joints via synchrotron X-ray tomography. Nat Biomed Eng 4, 343–354 (2020). https://doi.org/10.1038/s41551-019-0477-1
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