Frugal Approach toward Developing a Biomimetic, Microfluidic Network-on-a-Chip for In Vitro Analysis of Microvascular Physiology

Abstract

Several disease conditions, such as cancer metastasis and atherosclerosis, are deeply connected with the complex biophysical phenomena taking place in the complicated architecture of the tiny blood vessels in human circulatory systems. Traditionally, these diseases have been probed by devising various animal models, which are otherwise constrained by ethical considerations as well as limited predictive capabilities. Development of an engineered network-on-a-chip, which replicates not only the functional aspects of the blood-carrying microvessels of human bodies, but also its geometrical complexity and hierarchical microstructure, is therefore central to the evaluation of organ-assist devices and disease models for therapeutic assessment. Overcoming the constraints of reported resource-intensive fabrication techniques, here, we report a facile, simple yet niche combination of surface engineering and microfabrication strategy to devise a highly ordered hierarchical microtubular network embedded within a polydimethylsiloxane (PDMS) slab for dynamic cell culture on a chip, with a vision of addressing the exclusive aspects of the vascular transport processes under medically relevant paradigms. The design consists of hierarchical complexity ranging from capillaries (∼80 μm) to large arteries (∼390 μm) and a simultaneous tuning of the interfacial material chemistry. The fluid flow behavior is characterized numerically within the hierarchical network, and a confluent endothelial layer is realized on the inner wall of microfluidic device. We further explore the efficacy of the device as a vascular deposition assay of circulatory tumor cells (MG-63 osteosarcoma cells) present in whole blood. The proposed paradigm of mimicking an in vitro vascular network in a low-cost paradigm holds further potential for probing cellular dynamics as well as offering critical insights into various vascular transport processes.