A biomimetic microfluidic model to study signalling between endothelial and vascular smooth muscle cells under hemodynamic conditions

Engeland, Nicole C. A. van; Pollet, Andreas; Toonder, Jaap M.J. den; Bouten, Cvc Carlijn; Stassen, Oscar M. J. A.; Sahlgren, Cecilia

doi:10.1039/c8lc00286j

Cited by 95 publications

(92 citation statements)

References 63 publications

(111 reference statements)

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“…For example, the regulation of endothelial cell properties is not only governed by imposed mechanical forces but also influenced by the stiffness of the substrate to which the endothelial cells are adhered [ 68 ]. Many have improved on the inherently rigid substrate by culturing cells on a thin layer of more compliant material such as functionalised polyacrylamide hydrogels [ 69 ] or polydimethylsiloxane (PDMS) [ 70 ] to imitate the in vivo environment. It is plausible that these techniques could be incorporated into the model by culturing cells on a biomimetic surface within the wells, although no studies have combined the methods to our knowledge.…”

Section: Advantages and Limitations Of The Swirling Well Methodsmentioning

confidence: 99%

Understanding mechanobiology in cultured endothelium: A review of the orbital shaker method

Warboys¹,

Ghim²,

Weinberg

2019

Atherosclerosis

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A striking feature of atherosclerosis is its highly non-uniform distribution within the arterial tree. This has been attributed to variation in the haemodynamic wall shear stress (WSS) experienced by endothelial cells, but the WSS characteristics that are important and the mechanisms by which they lead to disease remain subjects of intensive investigation despite decades of research. In vivo evidence suggests that multidirectional WSS is highly atherogenic. This possibility is increasingly being studied by culturing endothelial cells in wells that are swirled on an orbital shaker. The method is simple and cost effective, has high throughput and permits chronic exposure, but interpretation of the results can be difficult because the fluid mechanics are complex; hitherto, their description has largely been restricted to the engineering literature. Here we review the findings of such studies, which indicate that putatively atherogenic flow characteristics occur at the centre of the well whilst atheroprotective ones occur towards the edge, and we describe simple mathematical methods for choosing experimental variables that avoid resonance, wave breaking and uncovering of the cells. We additionally summarise a large number of studies showing that endothelium cultured at the centre of the well expresses more pro-inflammatory and fewer homeostatic genes, has higher permeability, proliferation, apoptosis and senescence, and shows more endothelial-to-mesenchymal transition than endothelium at the edge. This simple method, when correctly interpreted, has the potential to greatly increase our understanding of the homeostatic and pathogenic mechanobiology of endothelial cells and may help identify new therapeutic targets in vascular disease.

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Section: Advantages and Limitations Of The Swirling Well Methodsmentioning

confidence: 99%

Understanding mechanobiology in cultured endothelium: A review of the orbital shaker method

Warboys¹,

Ghim²,

Weinberg

2019

Atherosclerosis

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“…This is achieved by simple perfusion of the biomolecules into the channel followed by appropriate incubation. Noncovalent immobilization is weaker than covalent bonding resulting in lower efficiency of the immobilization process and higher chance of biomolecule detachment from the surface at high shear stresses . In order to increase the yield of the immobilized proteins, the surface of the channels could be pre‐treated using plasma etching or ultraviolent (UV) light which promotes the physical attachment of the proteins by changing the surface energy of the substrate.…”

Section: Introductionmentioning

confidence: 99%

Biofunctionalization of Glass‐ and Paper‐Based Microfluidic Devices: A Review

Shakeri

Jarad

Leung

et al. 2019

Adv Materials Inter

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Biofunctionalization of microchannels is of great concern in the fabrication of microfluidic devices. Different substrates such as glass slides, papers, polymers, and beads require different biofunctionalization approaches granting the utilization of microfluidics in several biomedical applications. Covalent immobilization of biomolecules inside the microchannels is achieved by chemical modification of the surface such as silanization or introducing different coupling agents. Although creating biointerfaces that are covalently bonded to the microchannel surface necessitates multiple steps of surface modification and incubation times, it bestows a robust biointerface capable of withstanding high shear stresses and harsh conditions without dissipating the biofunctionality. Regarding the applications that do not require robustness and long‐term stability, noncovalent attachment of biomolecules such as van der Waals and hydrophobic interactions are adequate to successfully create a functional biointerface. This review summarizes the various biofunctionalization approaches used in the most common microfluidic substrates: glass and paper. In addition, several biofunctionalization examples are proposed and described in detail along with their associated applications.

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“…For instance, in the case of Bruch’s membrane, a structure located between the retinal pigment epithelium and choroidal capillaries of the eye, a membrane few-micron thick might be necesarry to better mimmic the structure 29 . A recent study also suggests that particularly thinner membranes might help to improve cell visualization when studying endothelial cell-smooth muscle cell interaction, specifically in studying cell signaling taking place in arterial walls under hemodynamic loading 30 . On the other side, control over pore size can be fundamental to study mechanisms such as cell migration, critically involved in various physiological activities such as maintenance of homoeostasis, immune responses, angiogenesis, adipogenesis and embryogenesis 31 – 34 .…”

Section: Introductionmentioning

confidence: 99%

Microfabricated tuneable and transferable porous PDMS membranes for Organs-on-Chips

Quiros-Solano

Gaio

Stassen

et al. 2018

Sci Rep

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We present a novel and highly reproducible process to fabricate transferable porous PDMS membranes for PDMS-based Organs-on-Chips (OOCs) using microelectromechanical systems (MEMS) fabrication technologies. Porous PDMS membranes with pore sizes down to 2.0 μm in diameter and a wide porosity range (2–65%) can be fabricated. To overcome issues normally faced when using replica moulding and extend the applicability to most OOCs and improve their scalability and reproducibility, the process includes a sacrificial layer to easily transfer the membranes from a silicon carrier to any PDMS-based OOC. The highly reliable fabrication and transfer method does not need of manual handling to define the pore features (size, distribution), allowing very thin (<10 μm) functional membranes to be transferred at chip level with a high success rate (85%). The viability of cell culturing on the porous membranes was assessed by culturing two different cell types on transferred membranes in two different OOCs. Human umbilical endothelial cells (HUVEC) and MDA-MB-231 (MDA) cells were successfully cultured confirming the viability of cell culturing and the biocompatibility of the membranes. The results demonstrate the potential of controlling the porous membrane features to study cell mechanisms such as transmigrations, monolayer formation, and barrier function. The high control over the membrane characteristics might consequently allow to intentionally trigger or prevent certain cellular responses or mechanisms when studying human physiology and pathology using OOCs.

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A biomimetic microfluidic model to study signalling between endothelial and vascular smooth muscle cells under hemodynamic conditions

Abstract: Cell signalling and mechanics influence vascular pathophysiology and there is an increasing demand for in vitro model systems that enable examination of signalling between vascular cells under hemodynamic conditions.

Cited by 95 publications

References 63 publications

Understanding mechanobiology in cultured endothelium: A review of the orbital shaker method

Understanding mechanobiology in cultured endothelium: A review of the orbital shaker method

Biofunctionalization of Glass‐ and Paper‐Based Microfluidic Devices: A Review

Microfabricated tuneable and transferable porous PDMS membranes for Organs-on-Chips

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