The role of fluid flow in targeted remodeling

Repetitive physiological loading generates fatigue microcracks in the solid matrix of bone. If left unrepaired, these fatigue microcracks can lead to complete fracture of the bone, however under normal circumstances these microcracks are repaired by a process called targeted remodeling. While the mechanism for initiation of targeted remodeling is not known, it may be linked to the mechanism bone tissue uses to sense its mechanical loading environment, i.e., the process of mechanotransduction. It is believed that bone senses its mechanical loading environment via load induced fluid flow, in particular by alterations in shear stress probably detected by osteocytes (cells embedded in the bone tissue that are believed to be the primary mechanosensor). However, since fluid flow velocity and the resultant shear stress can not be directly measured in the porous spaces of bone, computational models are used to determine these quantities. The goal of this study was to determine if alterations in fluid flow could be responsible for initiation of targeted remodeling. The main objectives of the study were to create a computational fluid dynamics model to determine if a fatigue microcrack can alter the fluid flow velocity profile in cortical bone and to use an in vitro fluid flow model to determine if altered fluid flow can affect biological responses important to targeted remodeling such as apoptosis, gene expression and nitric oxide and prostaglandin release.;Computational fluid dynamics models were created using a multi-level modeling approach to account for the differences between the loading occurring at the whole bone level and the fluid flow occurring at the cellular level. First, a milliscale model of a 1 mm X 1 mm section of cortical bone in the second metatarsal was created. The milliscale model included a discrete microcrack and Haversian canals in a regular array. The remainder of the tissue was represented as a homogenous porous media. Pressure boundary conditions were found by using beam bending theory and the maximum forces and moments occurring on the metatarsal during gait. Three different microcrack orientations (major axis oriented at 0, 45 and 90° to the loading direction) and two microcrack lengths (50 and 100 μm) were used. The results of the milliscale model, a fluid flow velocity profile, were used as boundary conditions for a more detailed, microscale model. The microscale model consisted of the central 340 X 240 μm portion of the milliscale model and included a discrete microcrack and lacunae, while canaliculi were represented as a homogeneous porous media. The results of the milliscale model indicate that fluid flow velocity is increased inside the microcrack, while fluid flow velocity decreases immediately outside the microcrack. The magnitude and location of these changes in velocity appear to be dependent upon the orientation of the microcrack. However, the amount of bone tissue affected is dependent upon the size of the microcrack, with longer cracks (100 μm) affecting as much as four times the amount of tissue as shorter cracks (50 μm). (Abstract shortened by UMI.).