Pneumatically Actuated Microfluidic Platform for Reconstituting 3D Vascular Tissue Compression

Abstract

In vivo, blood vessels constitutively experience mechanical stresses exerted by adjacent tissues and other structural elements. Vascular collapse, a structural failure of vascular tissues, may stem from any number of possible compressive forces ranging from injury to tumor growth and can promote inflammation. In particular, endothelial cells are continuously exposed to varying mechanical stimuli, internally and externally, resulting in blood vessel deformation and injury. This study proposed a method to model biomechanical-stimuli-induced blood vessel compression in vitro within a polydimethylsiloxane (PDMS) microfluidic 3D microvascular tissue culture platform with an integrated pneumatically actuated compression mechanism. 3D microvascular tissues were cultured within the device. Histological reactions to compressive forces were quantified and shown to be the following: live/dead assays indicated the presence of a microvascular dead zone within high-stress regions and reactive oxygen species (ROS) quantification exhibited a stress-dependent increase. Fluorescein isothiocyanate (FITC)-dextran flow assays showed that compressed vessels developed structural failures and increased leakiness; finite element analysis (FEA) corroborated the experimental data, indicating that the suggested model of vascular tissue deformation and stress distribution was conceptually sound. As such, this study provides a powerful and accessible in vitro method of modeling microphysiological reactions of microvascular tissues to compressive stress, paving the way for further studies into vascular failure as a result of external stress.