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.

Design and Optimizations of a High-throughput Valve-based Microfluidic Device for Single Cell Compartmentalization and Analysis

“…Actuating the microvalves to seal the cell-isolating chamber at lower pressure is seen advantageous since many cells respond to pressure and mechanical strain as well as to shear stress 26 . Several experimental observations have shown stress-dependent histological reactions of cell death, reactive oxygen species (ROS) level increases, as well as leaky vasculature 27 . Therefore, reduction of external pressure received by cells during experiment is important in managing stress and viability of the samples.…”

Microvascularized tumor organoids-on-chips: advancing preclinical drug screening with pathophysiological relevance

“…The self-morphogenic microvascular engineering method has been applied to the studies for the effects of various stimulations and constituents on the microvasculature. The angiogenic sprouting response to mechanical cues, including shear stress [ 76 ], interstitial flow [ 77 , 78 ], magnetic stimulation [ 79 ], and compression [ 80 ], was investigated using the self-organized microvasculature models. In the microvascular environment, the angiogenic sprouting was induced when a shear stress threshold was surpassed [ 76 ].…”

“…Also, low interstitial flow in the microfluidic system eliminated the spatial gradients of morphogen and maneuvered angiogenic growth [ 78 ]. Magnetic bead movement enhanced microvessels growth [ 79 ], while compressive force increased reactive oxygen species and vascular leakiness [ 80 ]. The response of the microvascular plexus subjected to other types of stimulation caused by nanoparticles [ 81 – 83 ], anti-neovasculogenic agents [ 84 ], fine particulate matter [ 85 ], and airborne nanoscale particles [ 86 ] was examined using the microfluidic models.…”

Bone‐on‐a‐Chip: Microfluidic Technologies and Microphysiologic Models of Bone Tissue

“…[ 98 ] In contrast to the EC cell lining technique, vasculogenesis and angiogenesis‐based methods can be combined with advanced microfluidic‐based techniques to recreate 3D microvascular networks that can be adapted into organ‐on‐a‐chip platforms. [ 99–105 ] A tri‐culture of human bone marrow mesenchymal stem cells (hBM‐MSCs), osteogenically differentiated (OD) hBM‐MSCs, and human umbilical vein endothelial cells (HUVECs) embedded in 2.5 mg mL −1 fibrin gel were used to recreate the bone microvasculature. [ 106 ] Experimental results showed the formation of functional microvascular networks after 4 days.…”