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Multiscale structure-functional modeling of musculoskeletal mineralized tissues

Member of the SPP1420 from 2009 till 2015


Musculoskeletal mineralized tissues (MMTs) are examples of natural materials achieving unique combinations of stiffness and strength. One of the striking features of MMTs is their ability to adapt to different functional demands by different structural arrangements of one common building block, the mineralized collagen fibril, at several levels of hierarchical organization. In the first funding period, we have applied multi-scale (from the nanoscale to the macroscale) and multimodal techniques to assess structure, composition, and elastic properties of various MMTs. Based on these data we have developed mathematical models and corresponding homogenization tools, that allow to estimate the elastic properties at different length scales (microscale, mesoscale, macroscale). This enables to decouple characteristic structural features from material properties and hence to study their respective impacts on the elastic functional behaviour at each scale. Within the second funding period we focus on the further improvement of the experimental techniques at the micron and submicron scales with the intention to increase the robustness of the experimental data. Moreover, we will systematically apply the models and computational tools to various MMTs and artificial hierarchical structures. Our ultimate goals are to provide public access to validated data of MMTs at different scales and to dedicated modelling tools as well as to infer generalized construction rules for the insilico design of hierarchically structured (biomimetic) composites with desired elastic properties.



Peer-reviewed Publications

  • R. Penta, A. Gerisch
    Investigation of the potential of asymptotic homogenization for elastic composites via a three-dimensional computational study.
    Computing and Visualization in Science, published online (2016).
  • R. Penta, A. Gerisch
    The asymptotic homogenization elasticity tensor properties for composites with material discontinuities.
    Continuum Mechanics and Thermodynamics, submitted (2015).
  • S. Bernard, J. Schneider, P. Varga, P. Laugier, K. Raum, Q. Grimal.
    Elasticity–density and viscoelasticity–density relationships at the tibia mid-diaphysis assessed from resonant ultrasound spectroscopy measurements.
    Biomechanics and Modeling in Mechanobiology. PMID: 26070349 (2015).
  • S. Checa, B. Hesse, P. Roschger, M. Aido, G. Duda. K. Raum, B. Willie.
    Skeletal maturation substantially affects elastic tissue properties in the endosteal and periosteal regions of loaded mice tibiae.
    Acta Biomaterialia, Volume 21 (2015), 154-164.
  • M. Granke, Q. Grimal, W.J. Parnell, K. Raum, A. Gerisch, F. Peyrin, A. Saïed, P. Laugier
    To what extent can cortical bone millimeter-scale elasticity be predicted by a two-phase composite model with variable porosity?
    Acta Biomaterialia, Volume 12 (2015), 207-215.
  • B. Hesse, P. Varga, M. Langer, S. Schrof, N. männicke, H. Suhonen, P. Maurer, P.Cloetens, F. Peyrin, K. Raum
    Canalicular network morphology is the major determinant of the spatial distribution of mass density in human bone tissue: evidence by means of synchrotron radiation phase-contrast nano-CT.
    Journal of Bone and Mineral Research, Volume 30 (2015), 346-356.
  • D. Rohrbach, Q. Grimal, P. Varga, F. Peyrin, M. Langer, P. Laugier, K. Raum  
    Distribution of mesoscale elastic properties and mass density in the human femoral shaft
    Connective Tissue Research, Volume 56 (2015), 120-132.
  • P. Varga, B. Hesse, M. Langer, S. Schrof, N. Männicke, H. Suhonen, A. Pacureanu, D. Pahr, F. Peyrin, K. Raum.
    Synchrotron X-ray phase nano-tomography-based analysis of the lacunar-canalicular network morphology and its relation to the strains experienced by osteocytes in situ as predicted by case-specific finite element analysis.
    Biomechanics and Modeling in Mechanobiology. Volume 14 (2015), 267-282.

  • S. Schrof, P. Varga, L. Galvis, K. Raum, A. Masic
    3D Raman mapping of the collagen fibril orientation in human osteonal lamellae.
    Journal of Structural Biology, Volume 187 (2014), 266-275.
  • S. Tiburtius, S. Schrof, F. Molnar, P. Varga, F. Peyrin, Q. Grimal, K. Raum, A. Gerisch
    On the elastic properties of mineralized turkey leg tendon tissue: multiscale model and experiment.
    Biomech Model Mechanobiol, Volume 13 (2014), 1003-1023.
  • B. Hesse, N. Männicke, A. Pacureanu, P. Varga, M. Langer, P. Maurer, F. Peyrin, K. Raum.
    Accessing osteocyte lacunar geometrical properties in human jaw bone on the submicron length scale using synchrotron radiation μCT.
    Journal of Microscopy. Volume 255 (2014), 158-168.

  • P. Varga, A. Pacureanu, M. Langer, H. suhonen, B. Hesse, Q. Grimal, P. Cloetens, K. Raum, F. Peyrin.
    Investigation of the 3D orientation of mineralized collagen fibrils in human lamellar bone using synchrotron X-ray phase nano-tomography.
    Acta Biomaterialia, Volume 9 (2013), 8118-8127.
  • M. Granke, A. Gourrier, F. Rupin, K. Raum, F. Peyrin, M. Burghammer, A. Saïed, P. Laugier.
    Microfibril orientation dominates the microelastic properties of human bone tissue at the lamellar length scale.
    PLoS One. Volume 8 (2013), e58043.

  • D. Rohrbach, S. Lakshmanan, F. Peyrin, M. Langer, A. Gerisch, Q. Grimal, P. Laugier, K. Raum
    Spatial distribution of tissue level properties in a human femoral cortical bone.
    Journal of Biomechanics, Volume 45 (2012), 2264-2270.

  • K. Raum, Q. Grimal, P. Laugier, A. Gerisch
    Multiscale structure-functional modeling of lamellar bone.
    Proceedings of Meetings on Acoustics (POMA), Volume 9 (2011), 020005-020005-15.
  • Q. Grimal, K. Raum, A. Gerisch, P. Laugier
    A determination of the minimum sizes of representative volume elements for the prediction of cortical bone elastic properties.
    Biomech Model Mechanobiol, Volume 10 (2011), 925-937.
  • B. Preininger, S. Checa, F.L. Molnar, P. Fratzl, G.N. Duda, K. Raum:
    Spatial-Temporal Mapping of Bone Structural and Elastic Properties in a Sheep Model Following Osteotomy.
    Ultrasound in Medicine and Biology, Volume 37 (2011), 474-483.

  • F. Rupin, A. Saied, D. Dalmas, F. Peyrin, S. Haupert, K. Raum, E. Barthel, G. Boivin, P. Laugier:
    Assessment of microelastic properties of bone using scanning acoustic microscopy: A face-to-face comparison with nanoindentation.
    Japanese Journal of Applied Physics, Volume 48 (2009).

Proceedings and Book Chapters

  • R. Penta and P. Mascheroni.
    The role of the angiogenic network structure on diffusion and consumption of anti-cancer drugs.
    4th International Conference on Computational and Mathematical Biomedical Engineering - CMBE2015,
    p. 186-189 in: CMBE 2015 Proceedings, P. Nithiarasu, E. Budyn (Eds.), 2015.
  • R. Penta and D. Ambrosi.
    The role of microvascular tortuosity in tumor transport phenomena and future perspective for drug delivery.
    PAMM, Volume 15 (2015), 101-102.
  • S. Schrof, P. Varga, B. Hesse, A. Masic, K. Raum.
    Three-dimensional investigation of the relationship between orientation and microelastic properties of mineralized collagen fibrils in human osteonal bone.
    In 6th European Symposium on Ultrasonic Characterization of Bone (ESUCB 2015)
    IEEE. doi:10.1109/esucb.2015.7169897.
  • A. Müller, B. Hesse, H. Castillo-Michel, M. Cotte, K. Raum
    Impact of chemical composition on microscale elastic properties of cortical bone - A site-matched FTIR-SAM study.
    In 6th European Symposium on Ultrasonic Characterization of Bone (ESUCB 2015)
    IEEE. doi: 10.1109/ESUCB.2015.7169898.
  • K. Raum:
    Microscopic elastic properties, Chapter 16 in “Bone Quantitative Ultrasound”,
    Laugier, P.; Haïat, G. (Eds.), Springer, 2011.
  • M. Mouchet, A. Gourrier, F. Rupin, K. Raum, F. Peyrin, A. Saïed, P, Laugier:
    Cortical bone microelasticity assessed with scanning acoustic microscopy. Relationship to nanostructural characteristics across a human osteon.
    Proceedings of the 3rd International Conference on the Development of BME in
    Vietnam, 189-191, 2010.
  • D. Rohrbach, S. Lakshmanan, F. Peyrin, K. Raum:
    Spatial distribution of tissue mineralization and anisotropic tissue elastic constants in human femoral cortical bone.
    IFMBE Proceedings, Volume 25 (2009), 962-965.
  • K. Raum, Q. Grimal, A. Gerisch:
    Insight into the structure-function relationship of the bone lamellar unit through Finite Element modelling based on high-frequency SAM data.
    IFMBE Proceedings, Volume 25 (2009), 2246-2249.

Talks with citable abstracts (Alf Gerisch, Sara Tiburtius, R. Penta)

  • Multiscale modeling and numerical simulation of multiphase elastic composites with discontinuous material properties.
    EMI 2015, Stanford, USA, 2015.
  • Mathematical modelling and numerical simulation in mechanobiology.
    Treffen des MSB-Net Clusters Numerische Simulation, Hannover, Germany, 2013.
  • Uncertainty Quantification Using Stochastic Collocation Method and Application in a Model of Mineralized Turkey Leg Tendon.
    18th International Symposium on Computational Biomechanics, Ulm, 2013.
  • Prediction of Effective Elastic Properties of Osteons by Means of Multiscale Models and Homogenization Methods.
    SIAM Conference on the Life Sciences, San Diego, USA, 2012.
  • Numerical homogenization in multi-scale models of musculoskeletal mineralized tissues.
    Comsol Conference, Stuttgart, 2011.
  • A multiscale model of mineralized fibril bundles - a homogenization approach.
    ECMTB 2011, Krakow, Poland, 2011.
  • A Micromechanical Model of the Mineralized Collagen Fibril Bundle with
    Application to Mineralized Turkey Leg Tendon Data.
    ICIAM 2011, Vancouver, Canada, 2011.
  • A multiscale model of mineralized turkey leg tendon - a homogenization approach.
    SimOrtho, Rostock, Germany, 2011.
  • Numerical homogenization in multi-scale models of musculoskeletal mineralized tissues.
    ACOMEM 2011, University of Liège, Belgium, 2011.

Invited Talks (Alf Gerisch, PI)

  • Multiscale Models and Homogenization for the Characterization of Mechanical Properties of Muskuloskeletal Mineralized Tissues.
    Applied Mathematics Seminars, University of Warwick, UK, 2015.
  • An adaptive stochastic collocation approach to uncertainty quantification.
    ICMS Workshop on Numerical Methods and Emerging Computational Challenges in
    Mathematical Biology, Dundee, UK, 2014.
  • Numerical challenges in models of tissue-scale tumour cell invasion.
    Workshop Metastasis and Angiogenesis, Mathematical Biosciences Institute,
    Columbus, Ohio, USA, 2014.
  • Mathematical modelling and numerical simulation of mechanical properties of muskuloskeletal mineralized tissues.
    Conference and Workshop on Modelling and Computation in Musculoskeletal Engineering (MCME),
    Brisbane, Australia, 2012.

Invited Talks (Kay Raum, PI)

  • Multiscale Assessment of Cortical Bone Properties with Quantitative Ultrasound.
    169th Meeting of the Acoustical Society of America, Pittsburgh, USA, May 2015.
  • Synchrotron Radiation Phase-Contrast Nano-CT Reveals 3D Bone Pore and Matrix Properties at the Nanoscale.
    Osteologie 2015, Berlin, March 2015.
  • Multimodal and multiscale assessment of bone properties.
    International Workshop Multiscale Models in Mechano and Tumor Biology Modeling, Homogenization, and Applications
    Darmstadt, Sept. 2015
  • Short Course: Mechanical Properties of Bone
    IEEE International Ultrasonics Symposium, Dresden, Oct. 2012.
  • Multiscale elastic imaging & modeling of musculoskeletal tissues.
    The Acoustics 2012,Hong Kong, May 2012.
  • Characterization of bone:acoustic microscopy
    13th World Congress of Ultrasound, 23rd Euroson and 35th Dreiländertreffen, Vienna, August, 2011.

Invited Talks (Raimondo Penta, PostDoc, TU Darmstadt)

  • Investigation of multiphase composites via asymptotic homogenization and its application to the bone hierarchical structure.
    Multiscale Models in Mechano and Tumor Biology: Modeling, Homogenization, and Applications, TU Darmstadt, Darmstadt, Germany, 2015.
  • Effective governing equations for poroelastic growing media.
    Porous Media Modelling in Biological Processes: Perspectives on Analytical  and Computational Methods Enabling Data Inversion, Dundee, UK, 2015.
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