Bridging the gap in understanding bone at multiple length scales using fluid dynamics

Fluid flow through the network of pathways in bone tissue is hypothesized to play an integral role in transducing external mechanical forces from the skeletal level down to the cells embedded deep within bone tissue. Communicating these external forces to bone cells is thought to be the mechanism by which bone is regenerated, and thus has major implications in fighting bone disease as well as repairing defects or damage to the tissue. This research pursues the role of fluid flow in bone remodeling and looks to bridge the gap between tissue and cellular level knowledge using computational fluid dynamics modeling of the Navier-Stokes equations as well as experimental validations of applicable models.; Using physiologic model geometries of increasing complexity, the following work predicts currently immeasurable properties of the tissue such as permeability or cell communication, as well as the resultant mechanical forces as they exist at the cellular and subcellular levels. The mechanical environment of the osteocyte is described, where the mode and magnitude of force on the cell varies spatio-temporally. Both hydrodynamic pressure and imparted shear stress are found on the cell surface, where the cell body experiences a nearly constant pressure and virtually zero shear stress while the cell processes are exposed to high gradients of both shear stress and pressure. This differentiation between types and location of forces has possible implications in cell physiology and the types of receptors or mechanosensors present on the cell. In addition, along the cell processes, which radiate from the cell body, subcellular geometries near the lower continuum-limit yield small discontinuities in the annular wall that are found to amplify peak shear stresses up to five times that of previous predictions. This result gives insight into a major paradox that has existed in bone and suggests a bridge between theoretical predictions and laboratory measurements of the necessary mechanical force for cell stimulation, where previous in vitro measurements have been an order of magnitude higher than in vivo predictions. This knowledge of the cell's mechanical environment is used to improve and design applications for laboratory cell studies and tissue growth in vitro.