Scanning transmission electron microscopic tomography of cortical bone using Z-contrast imaging

McNally, Elizabeth A.; Nan, Feihong; Botton, Gianluigi A.; Schwarcz, Henry P.

doi:10.1016/j.micron.2013.03.002

Cited by 51 publications

(63 citation statements)

References 30 publications

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“…Alternatively, electron microscopy and X‐ray diffraction studies on human cortical bone have led others to propose that the majority of mineral is present outside of collagen fibrils and in the interfibrillar compartment, in the form of elongated mineral plate structures (McNally et al. , ; Schwarcz et al. ).…”

Section: Discussionmentioning

confidence: 99%

“…Alternative proposed mechanisms for mineral nucleation include the precipitation and propagation of mineral crystals in the gap zone of collagen fibrils (Glimcher, 1987;Landis et al 1993;Nudelman et al 2010;Landis & Jacquet, 2013). Alternatively, electron microscopy and X-ray diffraction studies on human cortical bone have led others to propose that the majority of mineral is present outside of collagen fibrils and in the interfibrillar compartment, in the form of elongated mineral plate structures (McNally et al 2012(McNally et al , 2013Schwarcz et al 2014). The results of ion beam thinning to prepare hard tissue sections for TEM have been interpreted as showing that mineral enwraps the collagen micro-fibril and is therefore within the fibril but topologically outside the (tropo)collagen molecules, the mineral phase being present as extremely long features unrelated to the gap zone (Boyde, 1974;Boyde & Pawley, 1976).…”

Section: Discussionmentioning

confidence: 99%

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A distinctive patchy osteomalacia characterises Phospho1‐deficient mice

et al. 2017

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The phosphatase PHOSPHO1 is involved in the initiation of biomineralisation. Bones in Phospho1 knockout (KO) mice show histological osteomalacia with frequent bowing of long bones and spontaneous fractures: they contain less mineral, with smaller mineral crystals. However, the consequences of Phospho1 ablation on the microscale structure of bone are not yet fully elucidated. Tibias and femurs obtained from wild-type and Phospho1 null (KO) mice (25-32 weeks old) were embedded in PMMA, cut and polished to produce near longitudinal sections. Block surfaces were studied using 20 kV backscattered-electron (BSE) imaging, and again after iodine staining to reveal non-mineralised matrix and cellular components. For 3D characterisation, we used X-ray micro-tomography. Bones opened with carbide milling tools to expose endosteal surfaces were macerated using an alkaline bacterial pronase enzyme detergent, 5% hydrogen peroxide and 7% sodium hypochlorite solutions to produce 3D surfaces for study with 3D BSE scanning electron microscopy (SEM). Extensive regions of both compact cortical and trabecular bone matrix in Phospho1 KO mice contained no significant mineral and/or showed arrested mineralisation fronts, characterised by a failure in the fusion of the calcospherite-like, separately mineralising, individual micro-volumes within bone. Osteoclastic resorption of the uncalcified matrix in Phospho1 KO mice was attenuated compared with surrounding normally mineralised bone. The extent and position of this aberrant biomineralisation varied considerably between animals, contralateral limbs and anatomical sites. The most frequent manifestation lay, however, in the nearly complete failure of mineralisation in the bone surrounding the numerous transverse blood vessel canals in the cortices. In conclusion, SEM disclosed defective mineralising fronts and extensive patchy osteomalacia, which has previously not been recognised. These data further confirm the role of this phosphatase in physiological skeletal mineralisation.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

A distinctive patchy osteomalacia characterises Phospho1‐deficient mice

et al. 2017

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“…Cutting sections parallel or perpendicular to that long axis allow us to select either cross-sectional or longitudinal views of collagen fibrils and their associated minerals. Tomographic TEM analysis of sections [48], as well as use of a tilting stage in the microscope, allow us to make a link between the two sets of views.…”

Section: Orientation Of Sectionsmentioning

confidence: 99%

The Ultrastructure of Bone and Its Relevance to Mechanical Properties

2017

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Bone is a biologically generated composite material comprised of two major structural components: crystals of apatite and collagen fibrils. Computational analysis of the mechanical properties of bone must make assumptions about the geometric and topological relationships between these components. Recent transmission electron microscope (TEM) studies of samples of bone prepared using ion milling methods have revealed important previously unrecognized features in the ultrastructure of bone. These studies show that most of the mineral in bone lies outside the fibrils and is organized into elongated plates 5 nanometers (nm) thick, ∼80 nm wide and hundreds of nm long. These so-called mineral lamellae (MLs) are mosaics of single 5 nm-thick, 20-50 nm wide crystals bonded at their edges. MLs occur either stacked around the 50 nm-diameter collagen fibrils, or in parallel stacks of 5 or more MLs situated between fibrils. About 20% of mineral is in gap zones within the fibrils. MLs are apparently glued together into mechanically coherent stacks which break across the stack rather than delaminating. ML stacks should behave as cohesive units during bone deformation. Finite element computations of mechanical properties of bone show that the model including such features generates greater stiffness and strength than are obtained using conventional models in which most of the mineral, in the form of isolated crystals, is situated inside collagen fibrils.

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“…Bone mineral, or bone apatite, can be found inside the collagen fibril (intrafibrillar mineral) as well as surrounding it (extrafibrillar mineral) although their relative fractions are a matter of dispute . In a recently published analysis of the morphology of the mineral particles, obtained by 3D reconstruction of tomography data from ion‐milled bone slices, imaged by scanning transmission electron microscopy, classification in four hierarchical categories was made.…”

Section: Introductionmentioning

confidence: 99%

Biomineralization‐Inspired Material Design for Bone Regeneration

Pereira

Habibović

2018

Adv Healthcare Materials

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Synthetic substitutes of bone grafts, such as calcium phosphate–based ceramics, have shown some good clinical successes in the regeneration of large bone defects and are currently extensively used. In the past decade, the field of biomineralization has delivered important new fundamental knowledge and techniques to better understand this fascinating phenomenon. This knowledge is also applied in the field of biomaterials, with the aim of bringing the composition and structure, and hence the performance, of synthetic bone graft substitutes even closer to those of the extracellular matrix of bone. The purpose of this progress report is to critically review advances in mimicking the extracellular matrix of bone as a strategy for development of new materials for bone regeneration. Lab‐made biomimicking or bioinspired materials are discussed against the background of the natural extracellular matrix, starting from basic organic and inorganic components, and progressing into the building block of bone, the mineralized collagen fibril, and finally larger, 2D and 3D constructs. Moreover, bioactivity studies on state‐of‐the‐art biomimicking materials are discussed. By addressing these different topics, an overview is given of how far the field has advanced toward a true bone‐mimicking material, and some suggestions are offered for bridging current knowledge and technical gaps.

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Scanning transmission electron microscopic tomography of cortical bone using Z-contrast imaging

Cited by 51 publications

References 30 publications

A distinctive patchy osteomalacia characterises Phospho1‐deficient mice

A distinctive patchy osteomalacia characterises Phospho1‐deficient mice

The Ultrastructure of Bone and Its Relevance to Mechanical Properties

Biomineralization‐Inspired Material Design for Bone Regeneration

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