Atomic scale chemical tomography of human bone

Abstract

Human bone is a complex hierarchical material. Understanding bone structure and its corresponding composition at the nanometer scale is critical for elucidating mechanisms of biomineralization under healthy and pathological states. However, the three-dimensional structure and chemical nature of bone remains largely unexplored at the nanometer scale due to the challenges associated with characterizing both the structural and chemical integrity of bone simultaneously. Here, we use correlative transmission electron microscopy and atom probe tomography for the first time, to our knowledge, to reveal structures in human bone at the atomic level. This approach provides an overlaying chemical map of the organic and inorganic constituents of bone on its structure. This first use of atom probe tomography on human bone reveals local gradients, trace element detection of Mg, and the co-localization of Na with the inorganic-organic interface of bone mineral and collagen fibrils, suggesting the important role of Na-rich organics in the structural connection between mineral and collagen. Our findings provide the first insights into the hierarchical organization and chemical heterogeneity in human bone in three-dimensions at its smallest length scale – the atomic level. We demonstrate that atom probe tomography shows potential for new insights in biomineralization research on bone.

Atom Probe Tomography for 3D Structural and Chemical Analysis of Individual Proteins

“…We acknowledge that the porous nature of the silica structure introduces some uncertainties with regards to the reconstruction protocol, and poses risk of premature specimen failure. Somewhat surprisingly, nanoporous materials can, in many cases, be analyzed with reasonable accuracy using APT . We would intuitively expect differences in evaporation field between the protein and the surrounding silica matrix.…”

“…Most organic ions appear as molecular CNH 2 + and CO 2 + peaks in our spectra. Such ions stemming from organic fibers have been observed in prior investigations of dentin, enamel, and bone, and are seemingly characteristic of APT mass spectra from biomolecules in hard matrices.…”

Atom Probe Tomography: Development and Application to the Geosciences

“…Despite the potential difficulties with the preparation of atom probe analysis of biomaterials (Grandfield and Engqvist ), some of the earliest uses of laser‐assisted APT were on biogenic and hydroxyapatite, a common biomineral and a major constituent of bones and teeth (Gordon et al , , La Fontaine et al , Langelier et al ). These studies focussed on establishing the nanoscale compositional heterogeneity associated with the growth and trace element segregation associated with organic–inorganic interfaces and provided new insights into biogenic growth mechanisms and the processes responsible for dental decay.…”

Overcoming Challenges Associated with the Analysis of Nacre by Atom Probe Tomography

“…) and frequent fracturing (Langelier et al . ) have been reported. Therefore, in order to obtain a comprehensive and reliable set of information, a correlative characterisation approach was chosen in this study, combining FIB/SEM, TEM and APT.…”

“…), human bone (Langelier et al . ), and calcium carbonate from foraminifera (Branson et al . , Pérez‐Huerta and Laiginhas ).…”