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                <term xml:lang="en">Anisotropic stiffness</term>
                <term xml:lang="en">Bone extravascular matrix</term>
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              <p>Bone extravascular matrix (EVM) elasticity at several tens micrometer scale plays a key role in the mechanical behavior of bone at different length scales with implications on bone biology through mechanotransduction. The elastic properties of cortical bone EVM have been evaluated by several experimental methods, including nanoindentation, scanning acoustic microscopy (SAM) and mechanical testing on µm sized bone specimens. Nevertheless, these methods hardly give access to elastic anisotropy. In this work, we propose a novel inverse homogenization method to evaluate the anisotropic elastic properties of cortical bone EVM based on the transverse isotropic elastic tensor of millimeter-sized bone specimens measured by using resonant ultrasound spectroscopy and Fast Fourier Transform homogenization method. With the inverse homogenization method, the anisotropic EVM stiffness constants were evaluated on 50 human femoral cortical bone specimens from an elderly group. To our knowledge, this is the first time that the whole set of the EVM stiffness tensor is evaluated on the same specimen and on a large number of samples. Further comparison with the results from SAM and the degree of mineralization of bone (DMB) showed the potential of this method. Empirical laws between DMB and EVM anisotropic stiffness constants were also provided for the first time. With the anisotropic elasticity evaluated by the proposed method, more accurate models can be developed to better understand bone mechanics and biology, such as mechanotransduction.</p>
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