Fig. 3: Engineered heart tissue models.

a (Top) EHT condensation around the central Teflon cylinder in casting molds between culture days 1 to 4. EHTs after transfer in a stretch apparatus to continue culture under unidirectional and cyclic stretch (10%, 2 Hz) [scale bars = 10 mm (top), 20 µm (bottom-1), 100 µm (bottom-2), 1 µm (bottom-3, 4)]. Reproduced with permission²⁸. Copyright 2002, Wolters Kluwer Health, Inc. (Bottom) EHTs consist of a dense network of mainly longitudinally oriented cell bundles. TEM of sarcomeric structures, cell–cell junctions, and basal membrane of cardiac myocytes in EHT. b Experimental design: early-stage or late-stage hiPSC-CMs and supporting fibroblasts were encapsulated in fibrin hydrogel to form tissues stretched between two elastic pillars and made to contract by electrical stimulation. Cross-sections taken to evaluate T-tubules [scale bars = 20 µm (left-1, 2, 3, 4), 500 µm (middle-top), 10 µm (middle-bottom), 10 µm (right)]. Reproduced with permission²⁹. Copyright 2018, Springer Nature. c Biowire II platform generating atrial and ventricular-specific, and heteropolar cardiac tissues [scale bars = 30 µm (left-top-1, 2), 0.5 mm (left-bottom-1), 200 µm (left-bottom-2), 2 mm (right)]. Reproduced with permission³⁰. Copyright 2019, Elsevier. d Large-scale EHT patches restoring heart function in a dose-dependent manner [scale bars = 2 mm (top-left), 20 µm (top-middle), 20 µm (top-right), 500 µm (bottom-1), 50 µm (bottom-2), 250 µm (bottom-3, 4)]. Reproduced with permission³¹. Copyright 2021, Wolters Kluwer Health, Inc. e Human engineered cardiac tissue (hECT) integrated with cardiac macrophages to enhance contractility (scale bars = 100 µm). Reproduced with permission³⁴. Copyright 2024, Elsevier. f Pre-vascularized cardiac patches improving in vivo perfusion and function [scale bars = 1 mm (top), 100 µm (bottom-1), 25 µm (bottom-2, 3, 4)]. Adapted with permission³⁵. Copyright 2024, Elsevier. A A-band, CD45 Leukocyte common antigen, CM Cardiomyocyte, cTnT Cardiac troponin T, Cx43 Connexin 43, DAPI 4′,6-diamidino-2-phenylindole, EC endothelial cell, H H-zone, hECT human engineered cardiac tissue, I I-band, iCF induced cardiac fibroblast from hiPSC, iCM induced cardiomyocyte from hiPSC, iMΦ induced macrophage from hiPSC, M M-line, mCherry fluorescent protein (red marker), MLC2a myosin light chain 2a, MLC2v myosin light chain 2v, SAA serum amyloid A, SR sarcoplasmic reticulum, TT T-tubule, WGA wheat germ agglutinin, YAP yes-associated protein, Z Z-line, α-actinin alpha-actinin