Cardiac Tissue Chips (CTCs) for Modeling Cardiovascular Disease

Rogers, Aaron J.; Miller, Jessica M.; Kannappan, Ramaswamy; Sethu, Palaniappan

doi:10.1109/tbme.2019.2905763

Cited by 30 publications

(31 citation statements)

References 67 publications

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“…The 3D culture system enables the co-culture of several cell types with ECs. Furthermore, this system can be combined with flow and has been used in a wide variety of contexts to date, e.g., for the characterization of intercellular signaling during pre-vascular network formation [ 58 ] and to mimic pressure-volume changes seen in the left ventricle in encapsulated cardiac cells [ 59 ]. Apart from 3D scaffold gels described above, there have been attempts to provide a tubular, vessel-like scaffold structure to ECs.…”

Section: In Vitro Systems To Model Flow Dynamics and Endothelial Wall Shear Stress (Wss)mentioning

confidence: 99%

Investigation of Wall Shear Stress in Cardiovascular Research and in Clinical Practice—From Bench to Bedside

Urschel

Tauchi

Achenbach

et al. 2021

IJMS

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In the 1900s, researchers established animal models experimentally to induce atherosclerosis by feeding them with a cholesterol-rich diet. It is now accepted that high circulating cholesterol is one of the main causes of atherosclerosis; however, plaque localization cannot be explained solely by hyperlipidemia. A tremendous amount of studies has demonstrated that hemodynamic forces modify endothelial athero-susceptibility phenotypes. Endothelial cells possess mechanosensors on the apical surface to detect a blood stream-induced force on the vessel wall, known as “wall shear stress (WSS)”, and induce cellular and molecular responses. Investigations to elucidate the mechanisms of this process are on-going: on the one hand, hemodynamics in complex vessel systems have been described in detail, owing to the recent progress in imaging and computational techniques. On the other hand, investigations using unique in vitro chamber systems with various flow applications have enhanced the understanding of WSS-induced changes in endothelial cell function and the involvement of the glycocalyx, the apical surface layer of endothelial cells, in this process. In the clinical setting, attempts have been made to measure WSS and/or glycocalyx degradation non-invasively, for the purpose of their diagnostic utilization. An increasing body of evidence shows that WSS, as well as serum glycocalyx components, can serve as a predicting factor for atherosclerosis development and, most importantly, for the rupture of plaques in patients with high risk of coronary heart disease.

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Section: In Vitro Systems To Model Flow Dynamics and Endothelial Wall Shear Stress (Wss)mentioning

confidence: 99%

Investigation of Wall Shear Stress in Cardiovascular Research and in Clinical Practice—From Bench to Bedside

Urschel

Tauchi

Achenbach

et al. 2021

IJMS

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“…In 2016, we modified this setup with an additional collagen I/Matrigel coating to adapt hiPSC-CMs to physiological hemodynamic stresses by gradually increasing the filling volume and “systolic” pressure over the course of 72 h [ 34 ]. In 2019, this biomimetic cardiac tissue model (BCTM) was further adapted in our lab to culture cardiac cells in 3D using fibrin gels suspended between two posts anchored on top of a PDMS membrane ( Figure 2 b) [ 35 ]. Using this setup, the researchers demonstrated that pressure–volume changes associated with cardiovascular development and disease could be accurately replicated in vitro.…”

Section: Cardiac Tissue Chipsmentioning

confidence: 99%

“…Using microfluidic approaches, several groups have developed both active and passive flow control valves that can be used to ensure pulsatile pumping and unidirectional flow, similar to that seen in the body [ 178 , 179 , 180 ]. Microfabrication techniques can also create alternatives to cardiac tissue via the development of pumps to generate pulsatile flow, similar to the heart [ 35 , 181 ]. In summary, fluidic circuits can be tailored via adjustments in geometry, perfusion rate, and organization, along with incorporating components, such as actuators and valves (both in tubing connecting different TCs and within the TC devices themselves), to meet perfusion and transport requirements.…”

Section: Challenges Associated With Design and Construction Of Micmentioning

confidence: 99%

Tissue Chips and Microphysiological Systems for Disease Modeling and Drug Testing

et al. 2021

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Tissue chips (TCs) and microphysiological systems (MPSs) that incorporate human cells are novel platforms to model disease and screen drugs and provide an alternative to traditional animal studies. This review highlights the basic definitions of TCs and MPSs, examines four major organs/tissues, identifies critical parameters for organization and function (tissue organization, blood flow, and physical stresses), reviews current microfluidic approaches to recreate tissues, and discusses current shortcomings and future directions for the development and application of these technologies. The organs emphasized are those involved in the metabolism or excretion of drugs (hepatic and renal systems) and organs sensitive to drug toxicity (cardiovascular system). This article examines the microfluidic/microfabrication approaches for each organ individually and identifies specific examples of TCs. This review will provide an excellent starting point for understanding, designing, and constructing novel TCs for possible integration within MPS.

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“…Carbon dioxide (CO 2 ) (40, 41), UV laser ablation (42), and micromilling (42,43) are also alternative methods for fabricating molds, microdevices, and patterning hydrogel surfaces (44,45). These methods eliminate the need for a photomask.…”

Section: Building Chip Models: Fabrication Techniques For Oocsmentioning

confidence: 99%

Biomimetic microsystems for cardiovascular studies

Inbody

Sinquefield

Lewis

et al. 2021

American Journal of Physiology-Cell Physiology

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Tissue culture platforms have been around for several decades and have enabled numerous key findings in the cardiovascular field. However, these platforms fail to recreate the mechanical and dynamic features found within the body. Organs-on-chips (OOCs) are cellularized microfluidic based devices that can mimic the basic structure, function, and responses of organs. These systems have been successfully utilized in disease, development, and drug studies. OOCs are designed to recapitulate the mechanical, electrical, chemical, and structural features of the in vivo microenvironment. Here, we review cardiovascular-themed OOC studies, design considerations, and techniques used to generate microtissues within these devices. Further, we will highlight the advantages of OOCs over traditional cell culture methods, discuss implementation challenges, and provide perspectives on the state of the field.

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Cardiac Tissue Chips (CTCs) for Modeling Cardiovascular Disease

Cited by 30 publications

References 67 publications

Investigation of Wall Shear Stress in Cardiovascular Research and in Clinical Practice—From Bench to Bedside

Investigation of Wall Shear Stress in Cardiovascular Research and in Clinical Practice—From Bench to Bedside

Tissue Chips and Microphysiological Systems for Disease Modeling and Drug Testing

Biomimetic microsystems for cardiovascular studies

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