According to a World Health Organization (WHO) report in 2017, [1] cardiovascular diseases (CVDs) are the foremost cause of mortality, with 85% attributed to stroke and heart attack (or myocardial infarction [MI]) worldwide. The 2019 American Heart Association report [2] indicates that CVD is the leading lethal disease in the U.S., with 840 768 deaths in 2016. There is one new MI case in the U.S. every 40 s, contributing to about $351 billion in costs in 2014À2015. [2] MI gradually develops and deteriorates into inflammation, apoptosis, and inelastic fibrous scar, eventually leading to congestive heart failure (CHF). [3] Due to cardiomyocytes' (CMs) limited regeneration and proliferation ability, the effective long-term MI and CHF treatment is transplantation. There were over 3500 candidates on the heart transplant waiting list by the end of 2020, according to the national data [4] from the USA. Department of Health and Human Services. Shortage of organ donation sources, organ storage and maintenance, and post-transplantation immunologic rejection are tricky issues that are difficult to solve. Reconstruction of cardiac tissue using 3D scaffold or scaffold-free techniques has emerged as a promising alternative treatment approach.Cardiac bioengineering aims to investigate or rebuild illfunctioning myocardium tissues via CMs, scaffold-free cell sheet substrates, and implantable cell-seeded scaffolds. [3] Scaffold-free approaches include miRNA clusters, [5] spheroid models, [6] scaffold-free multiple-component cell cultures, [3,7] injectable hydrogels, [8] and organ on a chip. [9] These strategies permit direct delivery of cells or cell composites to infarcted myocardium and enable thick 3D tissue patch implantation with enhanced cell engraftment capacity. Some scaffold-free approaches can also be exploited in in vitro pathological cardiac models or ex vivo platforms for new therapy efficacy and cardiotoxicity evaluation. [6,7,9] Unlike scaffold-free pathways, cardiac scaffolds provide mechanical support to the myocardium, establish contractility/pumping, and lessen myocardial dilation and myocardial wall stress. [3] Meanwhile, significant progress has been made in stem cellderived CM tissue preparation; [10][11][12] scaffold and extracellular matrix (ECM) construction; [13][14][15][16][17] scaffold-free in situ injectable pathway development; [5][6][7]9] cell seeding, proliferation, and viabil-
