2. Are all osteocytes equal? Multiscale modelling of cortical bone to characterise the mechanical stimulation of osteocytes.

Bone continuously adapts its internal structure to accommodate the functional demands of its mechanical environment. This process is orchestrated by a network of mechanosensitive osteocytes that respond to external mechanical signals and recruit osteoblasts and osteoclasts to alter bone mass to meet loading demands. Because of the irregular hierarchical microarchitecture of bone tissue, the precise mechanical stimuli experienced by osteocytes located in different regions of the tissue is not well-understood. The objective of this study is to characterise the local stimulus experienced by osteocytes distributed throughout the tissue structure. Our models predict that an inhomogeneous microstructural strain field contributes to osteocytes receiving vastly different stimuli at the cellular level, depending on their location within the microstructure. In particular, osteocytes located directly adjacent to micropores experienced strain amplifications in their processes of up to nine times the applied global strain. Furthermore, it was found that the principal orientation of lamellar regions was found to contribute significantly to the magnitude of the stimulus being received at the cellular level. These findings indicate that osteocytes are not equal in terms of the mechanical stimulus being received, and we propose that only a subset of osteocytes may be sufficiently stimulated to function as mechanoreceptors.