Human Ocular Angiogenesis-Inspired Vascular Models on an Injection-Molded Microfluidic Chip

Abstract

Angiogenic sprouting, which is the growth of new blood vessels from pre-existing vessels, is orchestrated by cues from the cellular microenvironment, such as spatially controlled gradients of angiogenic factors. However, current in vitro models are less scalable for in-depth studies of angiogenesis. In this study, a plastic-based microfluidic chip is developed to reconstruct in vitro 3D vascular networks. The main disadvantages of the preexisting system are identified, namely, the low productivity and difficulty of experiments, and a breakthrough is suggested while minimizing disadvantages. The selection of plastic materials contributes to the productivity and usability of in vitro devices. By adopting this material, this chip offers simple fluid patterning, facilitating the construction of a cell-culture microenvironment. Compared with previous systems, the chip, which can form both inward and outwardly radial vascular sprouting, demonstrates the growth of functional, morphologically integral microvessels. The developed angiogenic model yields dose-dependent results for antiangiogenic drug screening. This model may contribute significantly not only to vascular studies under normal and pathological conditions, but also to fundamental research on the ocular neovascularization. Furthermore, it can be applied as a tool for more practical, extended preclinical research, providing an alternative to animal experiments.

Keywords: 3D vascular networks; alternative to animal testing; microfluidics; organs-on-chips; scale-up production.