02243nas a2200277   4500000000100000000000100001008004100002260001500043653001200058653002100070653001900091653001100110653003500121653002600156653002200182653002700204100001600231700001300247700001600260700001800276245007500294300001200369490000800381520156200389022001401951       2023                            d  c2023-02-1710aAnimals10aCardiomyopathies10aHeart Diseases10aHumans10ainduced pluripotent stem cells10aLab-On-A-Chip Devices10aMyocytes, Cardiac10aPluripotent Stem Cells1 aOmar Mourad1 aRyan Yee1 aMengyuan Li1 aSara S. Nunes00aModeling Heart Diseases on a Chip: Advantages and Future Opportunities  a483-4970 v1323 aHeart disease is a significant burden on global health care systems and is a leading cause of death each year. To improve our understanding of heart disease, high quality disease models are needed. These will facilitate the discovery and development of new treatments for heart disease. Traditionally, researchers have relied on 2D monolayer systems or animal models of heart disease to elucidate pathophysiology and drug responses. Heart-on-a-chip (HOC) technology is an emerging field where cardiomyocytes among other cell types in the heart can be used to generate functional, beating cardiac microtissues that recapitulate many features of the human heart. HOC models are showing great promise as disease modeling platforms and are poised to serve as important tools in the drug development pipeline. By leveraging advances in human pluripotent stem cell-derived cardiomyocyte biology and microfabrication technology, diseased HOCs are highly tuneable and can be generated via different approaches such as: using cells with defined genetic backgrounds (patient-derived cells), adding small molecules, modifying the cells' environment, altering cell ratio/composition of microtissues, among others. HOCs have been used to faithfully model aspects of arrhythmia, fibrosis, infection, cardiomyopathies, and ischemia, to name a few. In this review, we highlight recent advances in disease modeling using HOC systems, describing instances where these models outperformed other models in terms of reproducing disease phenotypes and/or led to drug development.  a1524-4571