Fig. 1: Multiscale overview of in vitro cardiac models, spanning single-cell systems to multi-organ platforms, and illustrating structural hierarchy (top), representative model platforms and their characteristics (middle), and major developmental and technological milestones in the field (bottom).
The top panel depicts cardiac organization across length scales, from subcellular structures and cardiomyocytes to myocardium, whole heart, and the circulation system. The middle panel summarizes major classes of in vitro cardiac models, including 2D monolayers, 3D engineered tissues, cardiac organoids, and microphysiological systems, highlighting their representative architectures, advantages, and limitations. The bottom timeline highlights key milestones in the evolution of in vitro cardiac models and is reproduced with permission from the indicated references (1991–2025); scale bars are shown for each representative image: (scale bar = 200 µm) 191(1991), (scale bar = 100 µm) 192(1997), 193(2000), (scale bar = 1 cm) 194(2002), (scale bar = 2 µm) 195(2004), [scale bars = 100 µm (left), 20 µm (right)] 196(2009), 20(2017), [scale bars = 100 µm (right-top), 20 µm (right-bottom)]29 (2018), (scale bar = 0.5 mm)30 (2019), (2021), [scale bars = 2 mm (left), 50 µm (right)]42 (2022), (2024), [scale bars = 2 mm (left), 1 cm (middle), 2 mm (right-top), 200 µm (right-bottom)]33 (2025). Red arrows indicate contraction direction; blue arrows, relaxation direction. SR sarcoplasmic reticulum, ECM extracellular matrix, AP action potential, EHT engineered heart tissue, hiPSC human induced pluripotent stem cells, CM cardiomyocyte, MPS microphysiological system, MΦ macrophage, EC endothelial cell
