Microfluidic and Organ-on-a-Chip Approaches to Investigate Cellular and Microenvironmental Contributions to Cardiovascular Function and Pathology

Abstract

Over the past decade, advances in microfabrication and biomaterials have facilitated the development of microfluidic tissue and organ models to address challenges with conventional animal and cell culture systems. These systems have largely been developed for human disease modeling and preclinical drug development and have been increasingly used to understand cellular and molecular mechanisms, particularly in the cardiovascular system where the characteristic mechanics and architecture are difficult to recapitulate in traditional systems. Here, we review recent microfluidic approaches to model the cardiovascular system and novel insights provided by these systems. Key features of microfluidic approaches include the ability to pattern cells and extracellular matrix (ECM) at cellular length scales and the ability to use patient-derived cells. We focus the review on approaches that have leveraged these features to explore the relationship between genetic mutations and the microenvironment in cardiovascular disease progression. Additionally, we discuss limitations and benefits of the various approaches, and conclude by considering the role further advances in microfabrication technology and biochemistry techniques play in establishing microfluidic cardiovascular disease models as central tools for understanding biological mechanisms and for developing interventional strategies.

Airway-On-A-Chip: Designs and Applications for Lung Repair and Disease

“…However, lung-on-a-chip devices are generally made of biological materials found in the ECM. Although other biomaterials have been used to create hydrogels in other organ-on-chip models [ 115 , 116 ], in 3D lung-on-a-chip devices, a few hydrogel materials have been reported, including collagen type I [ 27 ], Matrigel [ 22 ], decellularized ECM [ 28 ], and gelatin methacryloyl (GelMA) [ 25 ]. Collagen is one of the most ubiquitously used hydrogels, as it is the most common ECM constituent in the body [ 117 ].…”

Recent Advances in Cardiac Tissue Engineering for the Management of Myocardium Infarction

“…Patient-derived cells can also be used, as they require fewer numbers of cells than conventional methods. Both 2D and 3D structures can be effectively generated in the microfluidic chip with the help of surface coating or the use of hydrogels [183]. Such devices can be made to mimic cardiovascular physiology (including ECM structure, cell composition, electrophysiology, heart mechanics, vascularization, etc.)…”

Bioengineering Systems for Modulating Notch Signaling in Cardiovascular Development, Disease, and Regeneration

“…Microfluidics allows for the controlling of fluids that are confined to micro-sized dimensions [16]. Manipulation of the microenvironment with the microfluidics systems provides spatial and temporal positioning, precise nutrient/cytokine/drug supply to cells, and dynamic force cell culture [73].…”

“…Accordingly, understanding of the mechanisms of Notch signaling in the human cardiovascular system is still inconclusive, and progress is limited by the lack of ideal in vitro human models. To date, the advances of bioengineering systems and cell recourses from human-induced pluripotent stem cells (hiPSCs) provide unprecedented opportunities for precisely modeling and modulating Notch signaling in in vitro human cardiovascular systems, such as defined shear stressinduced mechanotransduction and crosstalk between co-cultured human cardiovascular cells in a microfluidics system [16], bioactive hydrogel for stem cell delivery in the injured myocardium [17], 3D spheroid culture [18], exosome and cell secretome for cardiovascular regeneration [19,20], and 3D bioprinting of biomaterials and cardiovascular cells [21].…”