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High resolution 3D structures of mineralized tissues in health and disease


A thorough knowledge of the structures of healthy mineralized tissues, such as bone or cartilage, is key to understanding the pathological changes occurring during disease. Such knowledge enables the underlying mechanisms that are responsible for pathology to be pinpointed. One high-resolution 3D method in particular — focused ion beam-scanning electron microscopy (FIB-SEM) — has fundamentally changed our understanding of healthy vertebrate mineralized tissues. FIB-SEM can be used to study demineralized matrix, the hydrated components of tissue (including cells) using cryo-fixation and even untreated mineralized tissue. The latter requires minimal sample preparation, making it possible to study enough samples to carry out studies capable of detecting statistically significant differences — a pre-requisite for the study of pathological tissues. Here, we present an imaging and characterization strategy for tissue structures at different length scales, describe new insights obtained on healthy mineralized tissues using FIB-SEM, and suggest future research directions for both healthy and diseased mineralized tissues.

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Fig. 1: 3D and 2D images of bone organs at different length scales.
Fig. 2: FIB-SEM as a tool to study bone material.
Fig. 3: FIB-SEM images of unprocessed mineralized osteonal cortical bone from a 7-month-old pig femur.
Fig. 4: Scheme showing the sequential steps for the proposed imaging and characterization strategy.
Fig. 5: FIB-SEM applied to a demineralized, fixed and stained sample of human lamellar bone.


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S.W. acknowledges the support of the Israel Science Foundation (grant No. 875/15). R.S. acknowledges the support of the Israel Science Foundation (grant No. 700/16) and the support of the Deutsche Forschungsgemeinschaft (grant No. ZA 557/5-1). The Menarini Foundation (Fondazione Internazionale Menarini) supported the Symposium Biomineralization in Health and Disease in Florence, Italy, which served as impetus and inspiration for this article.

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Correspondence to Steve Weiner.

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Weiner, S., Raguin, E. & Shahar, R. High resolution 3D structures of mineralized tissues in health and disease. Nat Rev Endocrinol 17, 307–316 (2021).

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