Mechanics of aortic smooth muscle cells in three-dimensional tissue constructs

Vascular smooth cells (VSMCs) in blood vessels are subjected to pulsatile stretching during each cardiac cycle. The response of VSMCs to global and local changes in mechanical and chemical cues may initiate structural changes in the vascular wall, and cause vascular diseases. Mixture models of vascular walls are used to study the response of VSMCs to different loading conditions and predict structural changes. However, the active and passive mechanics of VSMCs under physiological loading conditions are not well specified. Therefore, the goal of this dissertation is to measure the mechanics of VSMCs under cyclic (pulsatile) loading. Identifying the responses of VSMCs to cyclic loading can not only provide insight into vascular diseases, but these responses can also be incorporated into mixture models and used to find potential therapies for vascular diseases.;Bio-artificial tissue constructs were used as a simplified model system. Bovine aorta smooth muscle cells (baSMCs) were seeded into type I collagen or fibrin to make three-dimensional ring-shaped constructs. After six days of incubation in serum-containing media, the constructs were compact with elongated, aligned cells. Constructs were incubated for up to three additional days in media supplemented with Insulin-Transferrin-Selenium. Tissue constructs were cyclically stretched at one of four stretch amplitudes (1%, 2.5%, 5% and 10%) that approximated the range of physiological values. The cell stiffness decreased with increased stretch amplitude such that the peak cell force during each cycle was similar over the entire range of stretch amplitudes when constructs were cyclically stretched for more than 10 hours. A similar amplitude dependent change in stiffness was observed when constructs were cyclically shortened rather than stretched. Cell stiffness was also dependent on cyclic stretch amplitude when very slow length changes were superimposed on cyclic stretching or shortening. Finally, the experimental data were fitted to a microstructural model to quantify the observed trends in stiffness and peak forces.;The experimental data and fitted model parameters presented in this dissertation identify the response and adaptation of VSMCs to different loading conditions that may be incorporated into future mixture models of the vascular wall.