Multiscale Modeling Provides Differentiated Insights to Fluid Flow-Driven Stimulation of Bone Cellular Activities

摘要: Both the shape of bone organs and micro-architecture tissue are significantly influenced by prevailing mechanical loading. In this context, several most striking hence also debated issues relate to question how is actually able sense process its environment. Among other stimuli, it has been hypothesized that macroscopic loading induces pressure gradients in pore spaces tissue, these lead fluid flow exciting cells located spaces. Since vitro tests confirmed subjected surrounding indeed respond form altered expression activities, scientific community large part embraced ``fluid flow-hypothesis''. However, direct experimental evidence as actual occurrence sufficiently fast (in order reach cell responses observed vitro) not attained so far. paper, a multiscale modeling strategy presented (inspired well-established concept continuum micromechanics), allowing for upscaling (or homogenization) contributions canalicular, lacunar, vascular pores terms corresponding permeability tissue. The same model allows proceeding opposite way, namely downscaling macroscopically acting levels. Thus, physiologically relevant conditions can be related straightforwardly correspondingly arising pore-scale gradients, and, through considering resulting suitable transport laws, velocities. When comparing such computed velocities with were shown efficiently excite vitro, turns out pressure-driven canalicular probably potent stimulus osteocytes, whereas may required therein residing osteoblasts, osteoclasts, lining cells. conclusion, work thesis provides important, unprecedented insights observation scale-specific cellular mechanosensation bone.