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In situ characterization of nanoscale strains in loaded whole joints via synchrotron X-ray tomography

Nature Biomedical Engineering volume 4, pages 343–354 (2020)Cite this article

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Abstract

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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Fig. 1: Ultra-high-resolution sCT and DVC of intact joints.
Fig. 2: 3D strain mapping of intact tibia.
Fig. 3: Ultra-high-resolution sCT imaging of calcified cartilage.
Fig. 4: Correlative visualization of microstructure, strain patterns and fracture surfaces.
Fig. 5: Nano-resolved strain under physiologically representative loading before and after the onset of osteoarthritis.

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Data availability

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.

Code availability

The custom DVC code used in this study is available at https://zenodo.org/record/3228175#.XZdBRkZKguE.

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Acknowledgements

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.

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Author notes

  1. These authors contributed equally: Kamel Madi, Katherine A. Staines.

Authors and Affiliations

  1. Research Complex at Harwell, RAL, Didcot, UK

    Kamel Madi, Hua Geng & Peter D. Lee

  2. 3Dmagination Ltd, Harwell Oxford, Didcot, UK

    Kamel Madi

  3. School of Applied Sciences, Edinburgh Napier University, Edinburgh, UK

    Katherine A. Staines

  4. School of Mechanical, Industrial and Manufacturing Engineering, Oregon State University, Corvallis, OR, USA

    Brian K. Bay

  5. Comparative Biomedical Sciences, Royal Veterinary College, London, UK

    Behzad Javaheri & Andrew A. Pitsillides

  6. Department of Materials, The University of Manchester, Manchester, UK

    Hua Geng & Sarah Cartmell

  7. Diamond Light Source, Harwell Science and Innovation Campus, Oxfordshire, UK

    Andrew J. Bodey

  8. Mechanical Engineering, University College London, London, UK

    Peter D. Lee

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  1. Kamel Madi
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Contributions

Conception and design of the study: P.D.L., A.A.P., K.M., K.A.S. and B.K.B. Acquisition of data: K.M., B.K.B., H.G., B.J., K.A.S. and A.J.B. Interpretation of data, revision of the manuscript, final approval and agreement to be accountable for all aspects of the work: all authors. Drafting of the manuscript: K.A.S., K.M., B.K.B., A.A.P. and P.D.L.

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Correspondence to Brian K. Bay, Andrew A. Pitsillides or Peter D. Lee.

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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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