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Abstract: Animal models are widely used to gain insight into the role of genetics on bone structure and function. One of the main strategies to map the genes regulating specific traits is called quantitative trait loci (QTL) analysis, which generally requires a very large number of animals (often more than 1000) to reach statistical significance. QTL analysis for mechanical traits has been mainly based on experimental mechanical testing, which, in view of the large number of animals, is time consuming. Hence, the goal of the present work was to introduce an automated method for large-scale high-throughput quantification of the mechanical properties of murine femora. Specifically, our aims were, first, to develop and validate an automated method to quantify murine femoral bone stiffness. Second, to test its high-throughput capabilities on murine femora from a large genetic study, more specifically, femora from two growth hormone (GH) deficient inbred strains of mice (B6-lit/lit and C3.B6-lit/lit) and their first (F1) and second (F2) filial offsprings. Automated routines were developed to convert micro-computed tomography (micro-CT) images of femora into micro-finite element (micro-FE) models. The method was experimentally validated on femora from C57BL/6J and C3H/HeJ mice: for both inbred strains the micro-FE models closely matched the experimentally measured bone stiffness when using a single tissue modulus of 13.06GPa. The mechanical analysis of the entire dataset (n=1990) took approximately 44 CPU hours on a supercomputer. In conclusion, our approach, in combination with QTL analysis could help to locate genes directly involved in controlling bone mechanical competence. [Copyright &y& Elsevier]

Abstract: The inhomogeneous mineral content and its topographical distribution on a microscopic scale are major determinants of the mechanical quality of trabecular bone. The kinetics of bone tissue deposition and resorption together with the kinetics of the mineralization process determine the distribution of mineral in the tissue. The heterogeneity of the mineral content is described by the well-established bone mineralization density distribution (BMDD), which is experimentally accessible, e.g., using quantitative electron backscattering imaging (qBEI). In the present work, we demonstrate that the shape of the BMDD histogram of trabecular bone reflects directly the mineralization kinetics. Based on the experimental BMDD data of trabecular bone from healthy human adults and using a mathematical model for the remodeling and the mineralization process, the following main results were obtained. The peaked BMDD reflects necessarily a two-phase mineralization process with a fast primary phase and a slow secondary phase where the corresponding time constants differ three orders of magnitude. The obtained mineralization law, which describes the increase in the mineral content in a bone packet as a function of time, provides information not only about the initial mineralization surge, but also about the slow increase afterwards on the time scale of years. In addition to the mineralization kinetics the turnover rate of the remodeling process has a strong influence on the peak position and the shape of the BMDD. The described theoretical framework opens new possibilities for an analysis of experimentally measured BMDDs with respect to changes caused by diseases or treatments. It allows addressing whether changes in the BMDD have to be attributed to a variation in the turnover rate which consequently affects the density distribution or to a primary disorder in the mineralization process most likely reflecting alterations of the organic matrix. This is of important clinical interest because it helps to find therapeutic approaches directly targeting the primary etiological defects to correct the patients'' BMDD towards normal BMDD. [Copyright &y& Elsevier]

Functional gradients are material transitions that are found in nature and are known to result in materials with superior properties and multiple functionalities. The emerging multi-material 3D printing (=additive manufacturing, AM) techniques provide a powerful tool for the design and fabrication of bioinspired functionally graded materials (FGMs). In particular, the spatial distribution of materials can be controlled at the level of individual volumetric pixels (voxels i.e. , cubes with side lengths of 20–40 μm), thereby ensuring accuracy, reliability, and reproducibility of the obtained properties and allowing for systematic studies of how various design variables affect the deformation and fracture behaviors of FGMs. Here, we designed, 3D printed, and mechanically tested tensile and notched FGMs specimens with step-wise (i.e. , 5-, 10-, and 15-steps) and continuous (sigmoid and linear) gradients. The deformation and fracture mechanisms of these FGM composites were studied using digital image correlation, digital microscopy, and scanning electron microscopy. We further characterized the chemical composition and local mechanical properties of FGM composites using XPS and nanoindentation measurements, respectively. Tensile test specimens with a continuous gradient (i.e. , linear) exhibited much higher Young's moduli (≈3-folds) and ultimate strengths (≈2-folds) but lower elongations (≈2-folds drop) as compared to those with stepwise gradients (i.e. , 5-steps). Similarly, notched specimens with linear gradients exhibited 2-folds higher values of the stiffness and fracture stress, but 1.5-folds lower fracture strains as compared to those with 5-steps gradients. Although we found non-uniform highly concentrated strain distributions in all specimens, FGMs with linear gradients showed a smoother strain distribution and smaller crack blunting zones as compared to those with stepwise gradients. Our results imply that for stiffness and strength linear-gradient perform better than abrupt hard-soft-hard specimens. [ABSTRACT FROM AUTHOR]