Figure 1
The tough and living nature of human bone. (a, b) Fracture toughness and stiffness of a wide range of (a) synthetic engineering materials and (b) biological materials. A trade-off between these properties is often found in engineering materials, but is circumvented in materials made by living organisms. (c) Relative change in bone mass in different skeletal parts of the human body after resting in bed for 17 weeks. (d) Cross-sections of the metacarpal bone of an adult dog after 40 days of disuse compared to the normal structure. The metacarpal bone is positioned between the “wrist” and the toes. (e) X-ray images of two distinct femoral heads showing how the architecture of the trabeculae inside the bones (dark colour) follow the principal stress lines arising from mechanical loading. The red arrows and blue lines indicate the direction of tension and compression stresses, respectively. The example on top develops higher tensile stresses compared to compressive stresses. The situation inverts in the example shown at the bottom. Graphs (a) and (b) were adapted by Dr. Florian Bouville from Espinosa et al. [55. H.D. Espinosa, J.E. Rim, F. Barthelat and M.J. Buehler, Prog. Mater. Sci. 54, 1059 (2009).] Images (c–e) are adapted and reproduced with permission from Robling et al. [33. A.G. Robling, A.B. Castillo and C.H. Turner, Annual Review of Biomedical Engineering 8, 455 (2006).].
Figure 2
Synthesis and self-organization of collagen fibrils. (a) Fibroblasts synthesize collagen precursors in the endoplasmatic reticulum and secrete them into the extracellular space. (b) Multiple steps involved in the formation of collagen fibrils, including the synthesis and chemical modifications of procollagen chains, their folding into tropocollagen triple helices and self-organization into larger collagen fibrils. (c) Atomic Force Microscopy (AFM) image of a collagen fibril depicting its striated morphology derived from the staggered packing of tropocollagen triple helices. Adapted and reproduced with permission from Andriotis et al. [77. O.G. Andriotis, S.W. Chang, M. Vanleene, P.H. Howarth, D.E. Davies, S.J. Shefelbine, M.J. Buehler and P.J. Thurner, Journal of The Royal Society Interface 12, 20150701 (2015).].
Figure 3
Tutorial on the supramolecular chemistry of collagen fibrils [
1515. A.L. Boyle and D.N. Woolfson, in Supramolecular Chemistry: From Molecules to Nanomaterials, edited by P. A. Gale (John Wiley & Sons, Ltd., Hoboken, NJ, 2012).,
1616. D.B. Varshey, J.R.G. Sander, T. Frišcic and L.R. MacGillivray, in Supramolecular Chemistry: from Molecules to Nanomaterials, edited by J. W. Steed, P.A. Gale. (John Wiley & Sons, Ltd, Hoboken, NJ, 2012).,
1717. J. Bella, Biochem. J 473, 1001 (2016).,
1818. J.A. Fallas, J. Dong, Y.J. Tao and J.D. Hartgerink, J. Biol. Chem. 287, 8039 (2012).,
1919. S. Zhu, Q. Yuan, T. Yin, J. You, Z. Gu, S. Xiong and Y. Hu, Journal of Materials Chemistry B 6, 2650 (2018).]. All images except 3.2c are adapted and reproduced with permission from Zhu et al. and Hahn [
1919. S. Zhu, Q. Yuan, T. Yin, J. You, Z. Gu, S. Xiong and Y. Hu, Journal of Materials Chemistry B 6, 2650 (2018).,
2020. https://commons.wikimedia.org/wiki/File:Collagen_(tri ple_helix_protein_with_schematic_ribbons).jpg, accessed in Dec. 2020.
https://commons.wikimedia.org/wiki/File:...
]. Image 3.2.c was originally published in the Journal of Biological Chemistry [
1818. J.A. Fallas, J. Dong, Y.J. Tao and J.D. Hartgerink, J. Biol. Chem. 287, 8039 (2012).] ©.
Figure 4
Mechanism proposed for the biomineralization of bone tissue. (a) Osteoblasts produce intracellular vesicles loaded with amorphous calcium phosphate droplets and secrete them into the extracellular space. (b) Cryo-Scanning Electron Microscopy (SEM) image depicting an intracellular vesicle with multiple amorphous calcium phosphate droplets. Reproduced with permission from Addadi and Weiner [2525. L. Addadi and S. Weiner, Phys. Scr. 89, 098003 (2014).]. (c) Cell-controlled model for the biomineralization of collagen fibrils, highlighting the phase transformation from an amorphous precursor to oriented platelet-like crystals. (d) Energy landscape for the crystallization process, comparing the activation energies involved in the classical nucleation and growth theory (, dashed red line) and the phase transformation model ( and , continuous black line). (e) Transmission Electron Microscopy (TEM) image of a non-mineralized collagen fibril. The electron diffraction image shown in the inset indicates the absence of crystalline minerals in the collagen fibril. (f) TEM image of a mineralized collagen fibril. The electron diffraction displayed as inset shows diffraction peaks assigned to hydroxyapatite crystals that have their c-axis oriented parallel to the direction of the fibril. Images (e) and (f) are adapted and reproduced with permission from Nudelman et al. [2626. F. Nudelman, A.J. Lausch, N. Sommerdijk and E.D. Sone, Journal of Structural Biology 183, 258 (2013).].
Figure 5
The hierarchical structure of bone. (a) Schematics of the hierarchical architecture of bone, highlighting the main structural features of this biological tissue across multiple length scales. Adapted and reproduced with permission from Wegst et al. [4141. U.G.K. Wegst, H. Bai, E. Saiz, A.P. Tomsia and R.O. Ritchie, Nat. Mater. 14, 23 (2015).]. (b) Orientation of collagen fibrils within the cross-section of an osteon obtained from polarized Raman spectroscopy of bone tissue. The color code represents the average intensity of the amide I Raman band arising from the collagen molecules. (c) Intensity of the amide I Raman band as a function of the polarization angle of the incoming laser for different positions in the osteonal cross section. Adapted and reproduced with permission from Schrof et al. [4343. S. Schrof, P. Varga, L. Galvis, K. Raum and A. Masic, Journal of Structural Biology 187, 266 (2014).].
Figure 6
Strengthening and toughening mechanisms in cortical bone. (a) Measurements of the relative strain in the mineral platelets and in the mineralized collagen fibrils during tensile testing of a sample of bone tissue along the longitudinal direction. The relatively high strain detected in these structural elements demonstrate the importance of cooperative deformation mechanisms for the strength and stiffness of bone. (b) Schematic model depicting the transfer of stress to stiffer elements via shear stresses developed within the matrices (dashed lines) at multiple length scales. (c) Sketch and scanning electron microscopy image depicting the propagation of a crack along the transverse direction within a bone specimen (perpendicular to the orientation of osteons). In this orientation, strong crack deflection is observed at the cement lines around the osteons. (d) 3D tomographic reconstruction of a bone specimen during transverse fracture, highlighting twisting events that occur when the main crack hits osteons. (e) Resistance of cortical bone against crack propagation in the transverse (breaking) and longitudinal (splitting) directions as a function of crack extension (R-curves).
KIR represents the critical stress intensity factor required for crack growth (Figure
7). Figures a and b were adapted and reproduced with permission from Gupta et al. [
5555. H.S. Gupta, J. Seto, W. Wagermaier, P. Zaslansky, P. Boesecke and P. Fratzl, Proceedings of the National Academy of Sciences of the United States of America 103, 17741 (2006).]. Figures c and d were adapted and reproduced with permission from Koester et al. [
5757. K.J. Koester, J.W. Ager and R.O. Ritchie, Nat. Mater. 7, 672 (2008).].
Figure 7
Tutorial on the fracture mechanics of materials [5858. A. Bhaduri, Fracture (Springer, Singapore, 2018), vol. 264, p. 758.].
Figure 8
Bone adaptation modeled as a mechanostat. (a) Change in bone rigidity expected from adaptation depending on the local strain level developed within the tissue [5959. C.H. Turner, Bone 12, 203 (1991).]. (b) Negative feedback closed loop used to describe the adaptive behavior of bone [5959. C.H. Turner, Bone 12, 203 (1991).]. (c) Predictions of the mechanostat model and comparison with experimental data for bone under disuse followed by remobilization [5959. C.H. Turner, Bone 12, 203 (1991).]. (d) Schematics illustrating the cellular interactions involved in the control of bone resorption via the metabolic activity of osteoclasts [33. A.G. Robling, A.B. Castillo and C.H. Turner, Annual Review of Biomedical Engineering 8, 455 (2006).]. Stromal cells (blue) enhance or reduce the activity of osteoclasts (green) through the expression of the ligands RANKL or OPG, respectively. Graphs (a–c) were adapted and reproduced with permission from Turner [5959. C.H. Turner, Bone 12, 203 (1991).]. Drawing shown in (d) was adapted and reproduced with permission from Robling et al. [33. A.G. Robling, A.B. Castillo and C.H. Turner, Annual Review of Biomedical Engineering 8, 455 (2006).].
Figure 9
Bone remodeling process. (a) Schematics of the internal structure of the cellular agglomerates, known as Bone Multicellular Units (BMU), responsible for bone tissue remodeling. The network of osteocytes (1), osteoclasts (2), reversal cells (3) and osteoblasts (4) that form the BMU are indicated in the cartoon. Adapted and reproduced with permission from Studart [6565. A.R. Studart, Angewandte Chemie-International Edition 54, 3400 (2015).]. (b) The osteocyte network shown by a combination of optical microscopy, confocal microscopy and a computer-generated graphical representation. Adapted and reproduced with permission from Weinkamer et al. [6363. R. Weinkamer, P. Kollmannsberger and P. Fratzl, Current Osteoporosis Reports 17, 186 (2019).]. (c) Selected area of the network depicting (in red) nodes that form “highways” for fast nutrient and signal transmission throughout the tissue. Adapted and reproduced with permission from Weinkamer et al. [6363. R. Weinkamer, P. Kollmannsberger and P. Fratzl, Current Osteoporosis Reports 17, 186 (2019).]. (d) Expected gain in transmission speed for distinct types of bone depending on the ratio between the transport velocity in the network relative to the bone matrix. Adapted and reproduced with permission from Kollmannsberger et al. [6262. P. Kollmannsberger, M. Kerschnitzki, F. Repp, W. Wagermaier, R. Weinkamer and P. Fratzl, New Journal of Physics 19, 073019 (2017).]. (e) Dependence of the small-worldness index S on the network size (N) for the osteocyte lacunacanalicular system (colored dots) compared to other real-world networks (black and grey). Adapted and reproduced with permission from Kollmannsberger et al. [6262. P. Kollmannsberger, M. Kerschnitzki, F. Repp, W. Wagermaier, R. Weinkamer and P. Fratzl, New Journal of Physics 19, 073019 (2017).].
Figure 10
Tutorial on bone mechanotransduction [33. A.G. Robling, A.B. Castillo and C.H. Turner, Annual Review of Biomedical Engineering 8, 455 (2006)., 6666. C.T. Hung, F.D. Allen, S.R. Pollack and C.T. Brighton, Journal of Biomechanics 29, 1403 (1996)., 6767. K.K. Papachroni, D.N. Karatzas, K.A. Papavassiliou, E.K. Basdra and A.G. Papavassiliou, Trends in Molecular Medicine 15, 208 (2009)., 6868. E.U. Azeloglu and R. Iyengar, Cold Spring Harb Perspect Biol 7, a005934 (2015)., 6969. A. Wagner and D.A. Fell, Proceedings. Biological sciences 268, 1803 (2001).]. Images are adapted and reproduced with permission from Robling et al. [33. A.G. Robling, A.B. Castillo and C.H. Turner, Annual Review of Biomedical Engineering 8, 455 (2006).] and Papachroni et al. [6767. K.K. Papachroni, D.N. Karatzas, K.A. Papavassiliou, E.K. Basdra and A.G. Papavassiliou, Trends in Molecular Medicine 15, 208 (2009).].
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