Biomodeling of microvessels in a microfluidic chip

Abstract

Development of new approaches for modeling of blood vessels in vitro is an important trend which caused by the need to clarify the molecular mechanisms underlying the regulatory functions of the endothelium and mechanotransduction under the hydrodynamic conditions. We present a method for modeling of a symmetric bifurcation of a microvessel using microfluidics and cell technologies. A distinctive feature of our approach is the use of computational fluid dynamics (CFD) to calculate and to optimize the parameters of the microfluidic device based on physiological characteristics of bifurcations. CFD allows us to predict the hydrodynamic conditions for the endothelial lining in the microfluidic chip, e.g. wall shear stress intensity distribution. We showed here that the relatively simple procedure of micromechanical manufacturing of polymethyl methacrylate substrates is a consistent and cheap approach for the preparing of polymer replicas by subsequent soft lithography with enough reproducibility. We describe here the whole technology of creating of the closed multi-channel fluid system with changeable microfluidic chips capable of recycling of working fluid for well-controlled and long-term imitation of physiological and pathophysiological hydrodynamic conditions for endothelium. We demonstrate the usability of the system for the analysis of adhesion and growth of EA.hy926 endothelial-like cell line in the chip using intravital microscopy.