Transport of vascular endothelial growth factor dictates on-chip angiogenesis in tumor microenvironment

Abstract

On-chip investigations on tumor angiogenesis, hallmarked by the growth of new blood vessels from preexisting ones, have attracted significant interest in recent times, due to their exclusive capabilities of probing the detailed mechanisms of chemokine transport and visualization of cell-cell interactions that are otherwise challenging to capture and resolve under in vivo conditions. Here, we present a simulation study mimicking tumor angiogenesis microenvironment on-chip, with a vision of establishing the favorable conditions for stable and uniform gradients of vascular endothelial growth factor that plays a pivotal role in tumor progression. The model platform addresses different responses of endothelial cells such as chemotaxis, haptotaxis, and mitosis, under combined convection-diffusion transport in a micro-confined fluidic environment constituting collagen-based extracellular matrix. The model predictions emerge to be consistent with reported in vitro angiogenesis experiments and hold potential significance for the design of organ-on-a-chip assays, disease modeling, and optimizing anti-angiogenic therapies.