Electromechanical mechanisms of bone remodeling.

摘要

This dissertation studies the electromechanical coupling within live bone tissue in search for the bone remodeling mechanism. It covers the following topics: (i) the solid-fluid interaction within bone matrix under external loading; (ii) the generation of the streaming potential (SGP); (iii) the initiation and transmission of the intracellular electrical potential and current (induced by the extracellular streaming potential) in the bone cell network connected by gap junctions; (iv) experimentation with bone cell coupling in vitro.;First, an analytical solution of bone fluid pressure within a biphasic bone beam under oscillatory loading is derived based on a poroelastic analysis. This solution is then used to quantify the load-carrying capacity of the bone fluid pressure under various loading compositions. The strain generated streaming potential (SGP) can also be obtained as it is proportionally related to the bone fluid pressure.;Secondly, a cable model is formulated to calculate the intracellular potential and current within a one-dimensional array of osteocytic processes along the radius of an osteon. As a first approach, a continuous cable model is developed and analytically solved in which the gap junctional resistance is distributed uniformly along the cable length and the SGP (which serves as the extracellular potential) is evaluated using a beam analogy. All other parameters are evaluated based on a careful anatomical analysis.;Thirdly, a discrete cable model is developed to allow one discrete gap junction in the cable and take into account both the axisymmetric geometry of the osteon and the variation of the membrane time constant. The closed-form solution derived shows that the generation of the intracellular potential at the resting osteoblasts along the osteonal lumen can be interpreted as a combination of a high-pass and a low-pass filter with respect to loading frequency.;Finally, a flow chamber is designed, manufactured, and implemented as an in vitro experimental model to investigate the influence of fluid flow and shear stress on the coupling and the expression of gap junction proteins of rat osteosarcoma (ROS 17/2.8) cells.