Endothelial cell culture in microfluidic devices for investigating microvascular processes

Abstract

Numerous conditions and disease states such as sickle cell disease, malaria, thrombotic microangiopathy, and stroke significantly impact the microvasculature function and its role in disease progression. Understanding the role of cellular interactions and microvascular hemodynamic forces in the context of disease is crucial to understanding disease pathophysiology. models of microvascular disease using animal models often coupled with intravital microscopy have long been utilized to investigate microvascular phenomena. However, these methods suffer from some major drawbacks, including the inability to tightly and quantitatively control experimental conditions, the difficulty of imaging multiple microvascular beds within a living organism, and the inability to isolate specific microvascular geometries such as bifurcations. Thus, there exists a need for microvascular models that can mitigate the drawbacks associated with systems. To that end, microfluidics has been widely used to develop such models, as it allows for tight control of system inputs, facile imaging, and the ability to develop robust and repeatable systems with well-defined geometries. Incorporating endothelial cells to branching microfluidic models allows for the development of "endothelialized" systems that accurately recapitulate physiological microvessels. In this review, we summarize the field of endothelialized microfluidics, specifically focusing on fabrication methods, limitations, and applications of these systems. We then speculate on future directions and applications of these cutting edge technologies. We believe that this review of the field is of importance to vascular biologists and bioengineers who aim to utilize microfluidic technologies to solve vascular problems.

PDMS-Based Microfluidic Devices for Cell Culture

“…This means that before using microfluidic culture systems, operators must undergo extensive training in order to ensure correctness of the operations and to guarantee high reproducibility and reliability in the performed experiments. The complexity of daily operations-which could be addressed by improving the technology [72,73] by making more automated devices, such as by introducing actuators for liquid control or sensors for monitoring key parameters-can explain why the adoption of this system in standard practice has been slow. Development and standardization can take several years, but the more difficult point is the beginning, since it is not easy to convince people that have always been operating with certain protocols to move to something new, especially if this requires more training and can cause failures due to lack of experience.…”

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

“…[ 95 ] Endothelial cells (EC), as the building blocks of the circulatory system, have been integrated into many microfluidic systems to recreate a more physiologically relevant system. [ 96,97 ] We presented a 3D micromolding technique combined with EC cell lining technique to embed functional and perfusable microvessels inside various hydrogels and showed that the fabricated vascular network is efficient in improving mass transport and viability and differentiation of osteogenic cells in cell‐laden GelMA hydrogels. [ 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.…”

Microfluidics in Sickle Cell Disease Research: State of the Art and a Perspective Beyond the Flow Problem

“…Endothelialization refers to forming a 3-dimensional (3D) endothelial monolayer inside a microchannel to investigate endothelial and other cell interactions mimicking physiologically relevant processes ( Figure 3B ) ( Mannino et al, 2018 ). The endothelial monolayer is allowed to form after absorption of one of the extracellular matrix (ECM) proteins such as collagen, fibronectin (FN) or laminin (LN) that increases the adhesivity of endothelial cells to the microfluidics device material ( Myers et al, 2012 ).…”