EAGER: Which Mechanical Signals do Bone Micro Damage near Microcracks Send to Osteocytes?

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The research objective of this EArly-Concept Grant for Exploratory Research (EAGER) is to validate theoretical hypotheses on bone failure mechanism at the mineralised fibril level in order to precisely measure the in situ mechanical signals to bone cells (osteocytes) and to detect possible variations among humans in collagen and mineral strengths. Bone is a living tissue with a complex and highly heterogeneous microstructure resulting from the continuous self-healing process called remodeling. Osteocytes are mechano-sensitive cells suspected to initiate remodeling upon detection of micro damage in their environment that is composed of an organic phase of non-collagen proteins and collagen fibrils that are mineralised by hydroxyapatite crystals. Studies under this award will follow a top-down approach applying a dual experimental and numerical method to test and model micro cracks and micro damage growing in fresh human bone. The method will quantify in situ the local mechanical stress field created by progressing micro cracks and micro damage near osteocytes in bone under mechanical load. If successful, this research will determine how human bone mechanically bears load at the collagen and hydroxyapatite level and how the mechanical signals produced in situ by micro damage could possibly stimulate osteocytes to initiate the tissue biological response. The precise measurement of the mechanical effects of micro damage in the osteocyte's natural environment is transformative in that it advances the general understanding of the role of mechanical stimuli in cell biology. When applied to elderly patients this will further help to genetically trace the tissue mechanics changes in different components of bone to advance regenerative therapies and bone tissue engineering. The educational plan includes the mentoring of graduate students in bone micro biomechanics and an international collaboration with leading institutions in bone experimental research.