(69d) Engineering in Vitro Vascularization on a Chip

The process of forming 3-D microvessels in vitro is a key challenge in making regenerated tissue feasible and sustainable for tissue engineering. Recent microfabrication techniques, such as hydrogel modeling has facilitated the development of vascular network models in vitro. However, significant improvements such as rapid formation of the network need to be made for such models to be applied for regenerative medicine applications. In this investigation, we studied the effect of engineered human breast cancer cells on their ability to induce migration of human endothelial cells in an in vitro model. First, we developed a 3-D cellular spheroid model of the cancer cells in co-culture with human fibroblasts. We demonstrate the optimization and stability of the spheroids as a function of individual cell composition. Next, we developed a migration model in a collagen gel system and investigated the migration of the endothelial cells. Finally, we used a microfabricated chamber to study the formation of vascular networks in the presence of cancer cells. Our results show that the endothelial cell migration and network formation was greatly enhanced in the presence of cancer cells. We also present results from a mathematical model of the above system to quantify network formation as a function of cancer cell density. Our results suggest that engineered cancer cells be effective in vascularization of tissue constructs in vitro and can be used in regenerative medicine application.