In Vitro Cell Migration through Three-Dimensional Interfaces of Varying Depths, Widths, and Curvatures on...

Understanding how the injury morphology impacts endothelial repair is pivotal to curing vascular diseases. However, animal study or traditional two-dimensional wound healing models are limited to the simulation of three-dimensional (3D) injuries. In the present study, a cell migration model was established using a 3D micropatterned biochip. The biochip consisted of three functional regions, including a flat surface termed the cell seeding region to mimic a normal endothelial tissue, a region with a micropillar array termed the valve region that controlled cell migration due to hydrophobic forces, and an area with an array of micropits termed the cell migration region that simulated an impaired endothelial tissue. The sidewalls of the micropits simulated the interface between the normal tissue and impaired tissue. The migration behavior of two types of vascular cells, that is, endothelial cells (ECs) and vascular smooth muscle cells (VSMCs), in response to changes in the morphology of the injury interface, including depth, width, and curvature, was studied. The proportion of micropits occupied with cells at different time points was analyzed to reflect the difficulty that cells experience migrating into the target micropits. The results indicated that interfaces with a greater depth or width or having a lower curvature were more difficult for cells to traverse. A greater proportion of VSMCs was able to migrate over the pits than ECs. Additionally, it was found that the varying response of cells to the different interfaces was related to the cell geometry and cytoskeleton. On the basis of these results, we formed a better understanding of the repair mechanism of vascular endothelial injury.