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.
Highlights
In vivo, many cells in the human body continuously experience various mechanical stimuli.For example, endothelial cells (ECs) in blood vessels are exposed to varying mechanical stimuli, internally and externally
Endothelial cell sprouts induced by stromal cells resulted in end-to-end perfusible lumina, allowing for uninterrupted fluid flow through the vessel networks
This study presented a novel multi-layered microfluidic chip capable of reconstituting solid compressive stresses on cultivated blood vessels in vitro
Summary
Many cells in the human body continuously experience various mechanical stimuli. Endothelial cells (ECs) in blood vessels are exposed to varying mechanical stimuli, internally and externally. Mechanical stress causes EC phenotype alternation, vascular cytoskeletal remodeling, and disease progression [1]. Solid stress has a directional component as tissues have different structural characteristics depending on the location and orientation. The interactions between blood vessel networks and external solid stress remains comparatively under-investigated despite their importance to the fundamental understanding of many pathological conditions. Recent advancements in microfluidic microfabrication technologies have demonstrated the feasibility of generating in vitro vascular network models within microfluidic stromal and endothelial
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