Affiliation:
1. Laboratory for Living Systems Engineering, Department of Biomedical Engineering, USC Viterbi School of Engineering, University of Southern California, Los Angeles, California
2. Department of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California
Abstract
Many cardiovascular diseases are associated with pathological remodeling of the extracellular matrix (ECM) in the myocardium. ECM remodeling is a complex, multifactorial process that often contributes to declines in myocardial function and progression toward heart failure. However, the direct effects of the many forms of ECM remodeling on myocardial cell and tissue function remain elusive, in part because conventional model systems used to investigate these relationships lack robust experimental control over the ECM. To address these shortcomings, microphysiological systems are now being developed and implemented to establish direct relationships between distinct features in the ECM and myocardial function with unprecedented control and resolution in vitro. In this review, we will first highlight the most prominent characteristics of ECM remodeling in cardiovascular disease and describe how these features can be mimicked with synthetic and natural biomaterials that offer independent control over multiple ECM-related parameters, such as rigidity and composition. We will then detail innovative microfabrication techniques that enable precise regulation of cellular architecture in two and three dimensions. We will also describe new approaches for quantifying multiple aspects of myocardial function in vitro, such as contractility, action potential propagation, and metabolism. Together, these collective technologies implemented as cardiac microphysiological systems will continue to uncover important relationships between pathological ECM remodeling and myocardial cell and tissue function, leading to new fundamental insights into cardiovascular disease, improved human disease models, and novel therapeutic approaches.
Funder
American Heart Association (AHA)
The Saban Research Institute Team Science Grant
USC Women in Science and Engineering
USC Provost Fellowship
USC Annenberg Fellowship
USC Viterbi School of Engineering
Publisher
American Physiological Society
Subject
Physiology (medical),Cardiology and Cardiovascular Medicine,Physiology
Cited by
26 articles.
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