Roth, G. A. et al. Global burden of cardiovascular diseases and risk factors, 1990-2019: update from the GBD 2019 study. J. Am. Coll. Cardiol. 76, 2982–3021 (2020).
Blackwell, D. J., Schmeckpeper, J. & Knollmann, B. C. Animal models to study cardiac arrhythmias. Circ. Res. 130, 1926–1964 (2022).
Van Norman, G. A. Limitations of animal studies for predicting toxicity in clinical trials: is it time to rethink our current approach? JACC Basic Transl. Sci. 4, 845–854 (2019).
Kim, H., Kamm, R. D., Vunjak-Novakovic, G. & Wu, J. C. Progress in multicellular human cardiac organoids for clinical applications. Cell Stem Cell 29, 503–514 (2022).
Zhao, Y. et al. Integrating organoids and organ-on-a-chip devices. Nat. Rev. Bioeng. 2, 588–608 (2024).
Lind, J. U. et al. Cardiac microphysiological devices with flexible thin-film sensors for higher-throughput drug screening. Lab Chip 17, 3692–3703 (2017).
Zhao, Y. et al. A platform for generation of chamber-specific cardiac tissues and disease modeling. Cell 176, 913–927.e8 (2019).
Li, R. A. et al. Bioengineering an electro-mechanically functional miniature ventricular heart chamber from human pluripotent stem cells. Biomaterials 163, 116–127 (2018).
Lee, A. et al. 3D bioprinting of collagen to rebuild components of the human heart. Science 365, 482–487 (2019).
Ajdary, R. et al. Multifunctional 3D-printed patches for long-term drug release therapies after myocardial infarction. Adv. Funct. Mater. 30, 2003440 (2020).
Ronaldson-Bouchard, K. et al. Advanced maturation of human cardiac tissue grown from pluripotent stem cells. Nature 556, 239–243 (2018).
Dhahri, W. et al. In vitro matured human pluripotent stem cell-derived cardiomyocytes form grafts with enhanced structure and function in injured hearts. Circulation 145, 1412–1426 (2022).
Huebsch, N. et al. Metabolically driven maturation of human-induced-pluripotent-stem-cell-derived cardiac microtissues on microfluidic chips. Nat. Biomed. Eng. 6, 372–388 (2022).
Lemoine, M. D. et al. Human induced pluripotent stem cell-derived engineered heart tissue as a sensitive test system for QT prolongation and arrhythmic triggers. Circ. Arrhythm. Electrophysiol. 11, e006035 (2018).
Mathur, A. et al. Human iPSC-based cardiac microphysiological system for drug screening applications. Sci. Rep. 5, 8883 (2015).
Veldhuizen, J. et al. Modeling long QT syndrome type 2 on-a-chip via in-depth assessment of isogenic gene-edited 3D cardiac tissues. Sci. Adv. 8, eabq6720 (2022).
Veldhuizen, J. et al. Cardiac ischemia on-a-chip to investigate cellular and molecular response of myocardial tissue under hypoxia. Biomaterials 281, 121336 (2022).
Charwat, V. et al. Validating the arrhythmogenic potential of high-, intermediate-, and low-risk drugs in a human-induced pluripotent stem cell-derived cardiac microphysiological system. ACS Pharmacol. Transl. Sci. 5, 652–667 (2022).
Arslan, U. et al. Vascularized hiPSC-derived 3D cardiac microtissue on chip. Stem Cell Rep. 18, 2003 (2023).
Schneider, O. et al. Fusing spheroids to aligned μ-tissues in a heart-on-chip featuring oxygen sensing and electrical pacing capabilities. Mater. Today Bio 15, 100280 (2022).
Campbell, S. B. et al. Beyond polydimethylsiloxane: alternative materials for fabrication of organ-on-a-chip devices and microphysiological systems. ACS Biomater. Sci. Eng. 7, 2880–2899 (2021).
Vunjak-Novakovic, G., Ronaldson-Bouchard, K. & Radisic, M. Organs-on-a-chip models for biological research. Cell 184, 4597–4611 (2021).
Yang, H., Yang, Y., Kiskin, F. N., Shen, M. & Zhang, J. Z. Recent advances in regulating the proliferation or maturation of human-induced pluripotent stem cell-derived cardiomyocytes. Stem Cell Res. Ther. 14, 228 (2023).
Giacomelli, E. et al. Human-iPSC-derived cardiac stromal cells enhance maturation in 3D cardiac microtissues and reveal non-cardiomyocyte contributions to heart disease. Cell Stem Cell 26, 862–879.e11 (2020).
Bliley, J. M. et al. Dynamic loading of human engineered heart tissue enhances contractile function and drives a desmosome-linked disease phenotype. Sci. Transl. Med. 13, eabd1817 (2021).
Wimmer, R. A., Leopoldi, A., Aichinger, M., Kerjaschki, D. & Penninger, J. M. Generation of blood vessel organoids from human pluripotent stem cells. Nat. Protoc. 14, 3082–3100 (2019).
Wang, K. et al. Robust differentiation of human pluripotent stem cells into endothelial cells via temporal modulation of ETV2 with modified mRNA. Sci. Adv. 6, eaba7606 (2020).
Palikuqi, B. et al. Adaptable haemodynamic endothelial cells for organogenesis and tumorigenesis. Nature 585, 426–432 (2020).
Marian, A. J. & Braunwald, E. Hypertrophic cardiomyopathy: genetics, pathogenesis, clinical manifestations, diagnosis, and therapy. Circ. Res. 121, 749–770 (2017).
Wang, K. et al. Human engineered cardiac tissue model of hypertrophic cardiomyopathy recapitulates key hallmarks of the disease and the effect of chronic mavacamten treatment. Front. Bioeng. Biotechnol. 11, 1227184 (2023).
Green, E. M. et al. A small-molecule inhibitor of sarcomere contractility suppresses hypertrophic cardiomyopathy in mice. Science 351, 617–621 (2016).
Spertus, J. A. et al. Mavacamten for treatment of symptomatic obstructive hypertrophic cardiomyopathy (EXPLORER-HCM): health status analysis of a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet 397, 2467–2475 (2021).
Cashman, T. J., Josowitz, R., Johnson, B. V., Gelb, B. D. & Costa, K. D. Human engineered cardiac tissues created using induced pluripotent stem cells reveal functional characteristics of BRAF-mediated hypertrophic cardiomyopathy. PLoS ONE 11, e0146697 (2016).
Riaz, M. et al. Muscle LIM protein force-sensing mediates sarcomeric biomechanical signaling in human familial hypertrophic cardiomyopathy. Circulation 145, 1238–1253 (2022).
Lyon, R. C., Zanella, F., Omens, J. H. & Sheikh, F. Mechanotransduction in cardiac hypertrophy and failure. Circ. Res. 116, 1462–1476 (2015).
Marian, A. J. Molecular genetic basis of hypertrophic cardiomyopathy. Circ. Res. 128, 1533–1553 (2021).
Kinnear, C. et al. Myosin inhibitor reverses hypertrophic cardiomyopathy in genotypically diverse pediatric iPSC-cardiomyocytes to mirror variant correction. Cell Rep. Med. 5, 101520 (2024).
Muchtar, E., Blauwet, L. A. & Gertz, M. A. Restrictive cardiomyopathy: genetics, pathogenesis, clinical manifestations, diagnosis, and therapy. Circ. Res. 121, 819–837 (2017).
Wang, B. Z. et al. Engineered cardiac tissue model of restrictive cardiomyopathy for drug discovery. Cell Rep. Med. 4, 100976 (2023).
Schultheiss, H. P. et al. Dilated cardiomyopathy. Nat. Rev. Dis. Prim. 5, 32 (2019).
Wauchop, M. et al. Maturation of iPSC-derived cardiomyocytes in a heart-on-a-chip device enables modeling of dilated cardiomyopathy caused by R222Q-SCN5A mutation. Biomaterials 301, 122255 (2023).
Ma, Z. et al. Contractile deficits in engineered cardiac microtissues as a result of MYBPC3 deficiency and mechanical overload. Nat. Biomed. Eng. 2, 955–967 (2018).
Williams, B. Angiotensin II and the pathophysiology of cardiovascular remodeling. Am. J. Cardiol. 87, 10C–17C (2001).
Wang, E. Y. et al. An organ-on-a-chip model for pre-clinical drug evaluation in progressive non-genetic cardiomyopathy. J. Mol. Cell Cardiol. 160, 97–110 (2021).
Guo, J. et al. Substrate mechanics unveil early structural and functional pathology in iPSC micro-tissue models of hypertrophic cardiomyopathy. iScience 27, 109954 (2024).
Hamidzada, H. et al. Primitive macrophages induce sarcomeric maturation and functional enhancement of developing human cardiac microtissues via efferocytic pathways. Nat. Cardiovasc. Res. 3, 567–593 (2024).
Schwartz, P. J. et al. Inherited cardiac arrhythmias. Nat. Rev. Dis. Prim. 6, 58 (2020).
Ono, M. et al. Long QT syndrome type 2: emerging strategies for correcting class 2 KCNH2 (hERG) mutations and identifying new patients. Biomolecules 10, 1144 (2020).
Williams, K. et al. A 3-D human model of complex cardiac arrhythmias. Acta Biomater. 132, 149–161 (2021).
Drewitz, I. et al. Atrial fibrillation cycle length is a sole independent predictor of a substrate for consecutive arrhythmias in patients with persistent atrial fibrillation. Circ. Arrhythm. Electrophysiol. 3, 351–360 (2010).
Schwartz, P. J. & Woosley, R. L. Predicting the unpredictable: drug-induced QT prolongation and torsades de pointes. J. Am. Coll. Cardiol. 67, 1639–1650 (2016).
Kawatou, M. et al. Modelling torsade de pointes arrhythmias in vitro in 3D human iPS cell-engineered heart tissue. Nat. Commun. 8, 1078 (2017).
Ghosheh, M. et al. Electro-metabolic coupling in multi-chambered vascularized human cardiac organoids. Nat. Biomed. Eng. 7, 1493–1513 (2023).
Blinova, K. et al. International multisite study of human-induced pluripotent stem cell-derived cardiomyocytes for drug proarrhythmic potential assessment. Cell Rep. 24, 3582–3592 (2018).
Ibanez, B., Heusch, G., Ovize, M. & Van de Werf, F. Evolving therapies for myocardial ischemia/reperfusion injury. J. Am. Coll. Cardiol. 65, 1454–1471 (2015).
Welt, F. G. P. et al. Reperfusion injury in patients with acute myocardial infarction: JACC scientific statement. J. Am. Coll. Cardiol. 83, 2196–2213 (2024).
Chen, T. & Vunjak-Novakovic, G. Human tissue-engineered model of myocardial ischemia-reperfusion injury. Tissue Eng. Part A 25, 711–724 (2019).
Ottani, F. et al. Cyclosporine a in reperfused myocardial infarction: the multicenter, controlled, open-label CYCLE trial. J. Am. Coll. Cardiol. 67, 365–374 (2016).
Khalil, N. N. & McCain, M. L. Engineering the cellular microenvironment of post-infarct myocardium on a chip. Front. Cardiovasc. Med. 8, 709871 (2021).
Bannerman, D. et al. Heart-on-a-chip model of epicardial-myocardial interaction in ischemia reperfusion injury. Adv. Healthc. Mater. 13, e2302642 (2024).
Yadid, M. et al. Endothelial extracellular vesicles contain protective proteins and rescue ischemia-reperfusion injury in a human heart-on-chip. Sci. Transl. Med. 12, eaax8005 (2020).
Rexius-Hall, M. L. et al. A myocardial infarct border-zone-on-a-chip demonstrates distinct regulation of cardiac tissue function by an oxygen gradient. Sci. Adv. 8, eabn7097 (2022).
Richards, D. J. et al. Human cardiac organoids for the modelling of myocardial infarction and drug cardiotoxicity. Nat. Biomed. Eng. 4, 446–462 (2020).
Hannenhalli, S. et al. Transcriptional genomics associates FOX transcription factors with human heart failure. Circulation 114, 1269–1276 (2006).
Frangogiannis, N. G. Cardiac fibrosis. Cardiovasc. Res. 117, 1450–1488 (2021).
Wang, E. Y. et al. Biowire model of interstitial and focal cardiac fibrosis. ACS Cent. Sci. 5, 1146–1158 (2019).
Kong, M. et al. Cardiac fibrotic remodeling on a chip with dynamic mechanical stimulation. Adv. Healthc. Mater. 8, e1801146 (2019).
Mastikhina, O. et al. Human cardiac fibrosis-on-a-chip model recapitulates disease hallmarks and can serve as a platform for drug testing. Biomaterials 233, 119741 (2020).
Travers, J. G., Tharp, C. A., Rubino, M. & McKinsey, T. A. Therapeutic targets for cardiac fibrosis: from old school to next-gen. J. Clin. Invest. 132, e148554 (2022).
Leyva, F. et al. Myocardial fibrosis predicts ventricular arrhythmias and sudden death after cardiac electronic device implantation. J. Am. Coll. Cardiol. 79, 665–678 (2022).
MacKenna, D., Summerour, S. R. & Villarreal, F. J. Role of mechanical factors in modulating cardiac fibroblast function and extracellular matrix synthesis. Cardiovasc. Res. 46, 257–263 (2000).
Duan, Q. et al. BET bromodomain inhibition suppresses innate inflammatory and profibrotic transcriptional networks in heart failure. Sci. Transl. Med. 9, eaah5084 (2017).
Reyat, J. S. et al. Modelling the pathology and treatment of cardiac fibrosis in vascularised atrial and ventricular cardiac microtissues. Front. Cardiovasc. Med. 10, 1156759 (2023).
Hofbauer, P. et al. Cardioids reveal self-organizing principles of human cardiogenesis. Cell 184, 3299–3317.e22 (2021).
Landau, S. et al. Primitive macrophages enable long-term vascularization of human heart-on-a-chip platforms. Cell Stem Cell 31, 1222–1238.e10 (2024).
Ahrens, J. H. et al. Programming cellular alignment in engineered cardiac tissue via bioprinting anisotropic organ building blocks. Adv. Mater. 34, e2200217 (2022).
Bailey, A. L. et al. SARS-CoV-2 infects human engineered heart tissues and models COVID-19 myocarditis. JACC Basic Transl. Sci. 6, 331–345 (2021).
Marchiano, S. et al. SARS-CoV-2 infects human pluripotent stem cell-derived cardiomyocytes, impairing electrical and mechanical function. Stem Cell Rep. 16, 478–492 (2021).
Mills, R. J. et al. BET inhibition blocks inflammation-induced cardiac dysfunction and SARS-CoV-2 infection. Cell 184, 2167–2182.e22 (2021).
Lu, R. X. Z. et al. Vasculature-on-a-chip platform with innate immunity enables identification of angiopoietin-1 derived peptide as a therapeutic for SARS-CoV-2 induced inflammation. Lab Chip 22, 1171–1186 (2022).
Lu, R. X. Z. et al. Cardiac tissue model of immune-induced dysfunction reveals the role of free mitochondrial DNA and the therapeutic effects of exosomes. Sci. Adv. 10, eadk0164 (2024).
Giacca, M. & Shah, A. M. The pathological maelstrom of COVID-19 and cardiovascular disease. Nat. Cardiovasc. Res. 1, 200–210 (2022).
Bjorkegren, J. L. M. & Lusis, A. J. Atherosclerosis: recent developments. Cell 185, 1630–1645 (2022).
Shakeri, A. et al. Engineering organ-on-a-chip systems for vascular diseases. Arterioscler. Thromb. Vasc. Biol. 43, 2241–2255 (2023).
Su, C. et al. A novel human arterial wall-on-a-chip to study endothelial inflammation and vascular smooth muscle cell migration in early atherosclerosis. Lab Chip 21, 2359–2371 (2021).
Paloschi, V. et al. Utilization of an artery-on-a-chip to unravel novel regulators and therapeutic targets in vascular diseases. Adv. Healthc. Mater. 13, e2302907 (2024).
Deng, Y. et al. Studying the efficacy of antiplatelet drugs on atherosclerosis by optofluidic imaging on a chip. Lab Chip 23, 410–420 (2023).
Marder, M. et al. Stem cell-derived vessels-on-chip for cardiovascular disease modeling. Cell Rep. 43, 114008 (2024).
Maringanti, R. et al. Atherosclerosis on a chip: a 3-dimensional microfluidic model of early arterial events in human plaques. Arterioscler. Thromb. Vasc. Biol. 44, 2453–2472 (2024).
Helle, E. et al. HiPS-endothelial cells acquire cardiac endothelial phenotype in co-culture with hiPS-cardiomyocytes. Front. Cell Dev. Biol. 9, 715093 (2021).
Lother, A. et al. Cardiac endothelial cell transcriptome. Arterioscler. Thromb. Vasc. Biol. 38, 566–574 (2018).
Natividad-Diaz, S. L. et al. A combined hiPSC-derived endothelial cell and in vitro microfluidic platform for assessing biomaterial-based angiogenesis. Biomaterials 194, 73–83 (2019).
Vila Cuenca, M. et al. Engineered 3D vessel-on-chip using hiPSC-derived endothelial- and vascular smooth muscle cells. Stem Cell Rep. 16, 2159–2168 (2021).
Pandian, N. K. R., Mannino, R. G., Lam, W. A. & Jain, A. Thrombosis-on-a-chip: prospective impact of microphysiological models of vascular thrombosis. Curr. Opin. Biomed. Eng. 5, 29–34 (2018).
Zhang, Y. S. et al. Bioprinted thrombosis-on-a-chip. Lab Chip 16, 4097–4105 (2016).
Zhang, B. et al. Biodegradable scaffold with built-in vasculature for organ-on-a-chip engineering and direct surgical anastomosis. Nat. Mater. 15, 669–678 (2016).
Berry, J. et al. An “occlusive thrombosis-on-a-chip” microfluidic device for investigating the effect of anti-thrombotic drugs. Lab Chip 21, 4104–4117 (2021).
Brouns, S. L. N., Provenzale, I., van Geffen, J. P., van der Meijden, P. E. J. & Heemskerk, J. W. M. Localized endothelial-based control of platelet aggregation and coagulation under flow: a proof-of-principle vessel-on-a-chip study. J. Thromb. Haemost. 18, 931–941 (2020).
Akther, F., Fallahi, H., Zhang, J., Nguyen, N. T. & Ta, H. T. Evaluating thrombosis risk and patient-specific treatment strategy using an atherothrombosis-on-chip model. Lab Chip 24, 2927–2943 (2024).
Ju, L. A., Aye, S. S. S., Fang, Z., Wu, C.-L. M. & Lim, K. S. Integrating microfluidics, hydrogels, and 3D bioprinting for personalized vessel-on-a-chip platforms. Biomater. Sci. 13, 1131–1160 (2025).
Lim, H. Y., O’Malley, C., Donnan, G., Nandurkar, H. & Ho, P. A review of global coagulation assays — is there a role in thrombosis risk prediction? Thromb. Res. 179, 45–55 (2019).
Westein, E. et al. Atherosclerotic geometries exacerbate pathological thrombus formation poststenosis in a von Willebrand factor-dependent manner. Proc. Natl Acad. Sci. USA 110, 1357–1362 (2013).
Thomas, J., Kostousov, V. & Teruya, J. Bleeding and thrombotic complications in the use of extracorporeal membrane oxygenation. Semin. Thromb. Hemost. 44, 20–29 (2018).
Jain, A. et al. A shear gradient-activated microfluidic device for automated monitoring of whole blood haemostasis and platelet function. Nat. Commun. 7, 10176 (2016).
Qiu, Y. et al. Clinically relevant clot resolution via a thromboinflammation-on-a-chip. Nature 641, 1298–1308 (2025).
Zheng, Y., Chen, J. & Lopez, J. A. Flow-driven assembly of VWF fibres and webs in in vitro microvessels. Nat. Commun. 6, 7858 (2015).
Ingber, D. E. Human organs-on-chips for disease modelling, drug development and personalized medicine. Nat. Rev. Genet. 23, 467–491 (2022).
Huebsch, N. et al. Miniaturized iPS-cell-derived cardiac muscles for physiologically relevant drug response analyses. Sci. Rep. 6, 24726 (2016).
Lind, J. U. et al. Instrumented cardiac microphysiological devices via multimaterial three-dimensional printing. Nat. Mater. 16, 303–308 (2017).
Cho, S., Discher, D. E., Leong, K. W., Vunjak-Novakovic, G. & Wu, J. C. Challenges and opportunities for the next generation of cardiovascular tissue engineering. Nat. Methods 19, 1064–1071 (2022).
Prantil-Baun, R. et al. Physiologically based pharmacokinetic and pharmacodynamic analysis enabled by microfluidically linked organs-on-chips. Annu. Rev. Pharmacol. Toxicol. 58, 37–64 (2018).
Offeddu, G. S. et al. Microheart: a microfluidic pump for functional vascular culture in microphysiological systems. J. Biomech. 119, 110330 (2021).
Michas, C. et al. Engineering a living cardiac pump on a chip using high-precision fabrication. Sci. Adv. 8, eabm3791 (2022).
Park, J., Wu, Z., Steiner, P. R., Zhu, B. & Zhang, J. X. J. Heart-on-chip for combined cellular dynamics measurements and computational modeling towards clinical applications. Ann. Biomed. Eng. 50, 111–137 (2022).
Jaeger, K. H. et al. Improved computational identification of drug response using optical measurements of human stem cell derived cardiomyocytes in microphysiological systems. Front. Pharmacol. 10, 1648 (2019).
Aravindakshan, M. R., Mandal, C., Pothen, A., Schaller, S. & Maass, C. DigiLoCS: a leap forward in predictive organ-on-chip simulations. PLoS ONE 20, e0314083 (2025).
Lewis-Israeli, Y. R. et al. Self-assembling human heart organoids for the modeling of cardiac development and congenital heart disease. Nat. Commun. 12, 5142 (2021).
Rossi, G. et al. Capturing cardiogenesis in gastruloids. Cell Stem Cell 28, 230–240.e6 (2021).
Drakhlis, L. et al. Human heart-forming organoids recapitulate early heart and foregut development. Nat. Biotechnol. 39, 737–746 (2021).
Silva, A. C. et al. Co-emergence of cardiac and gut tissues promotes cardiomyocyte maturation within human iPSC-derived organoids. Cell Stem Cell 28, 2137–2152.e6 (2021).
Okhovatian, S., Mohammadi, M. H., Rafatian, N. & Radisic, M. Engineering models of the heart left ventricle. ACS Biomater. Sci. Eng. 8, 2144–2160 (2022).
Zhang, S., Wan, Z. & Kamm, R. D. Vascularized organoids on a chip: strategies for engineering organoids with functional vasculature. Lab Chip 21, 473–488 (2021).
Voges, H. K. et al. Vascular cells improve functionality of human cardiac organoids. Cell Rep. 42, 112322 (2023).
Wu, Q. et al. Flexible 3D printed microwires and 3D microelectrodes for heart-on-a-chip engineering. Biofabrication 15, 035023 (2023).
Reyes, D. R. et al. Accelerating innovation and commercialization through standardization of microfluidic-based medical devices. Lab Chip 21, 9–21 (2021).
Ewoldt, J. K. et al. Induced pluripotent stem cell-derived cardiomyocyte in vitro models: benchmarking progress and ongoing challenges. Nat. Methods 22, 24–40 (2025).
Feric, N. T. & Radisic, M. Maturing human pluripotent stem cell-derived cardiomyocytes in human engineered cardiac tissues. Adv. Drug Deliv. Rev. 96, 110–134 (2016).
Dessalles, C. A., Leclech, C., Castagnino, A. & Barakat, A. I. Integration of substrate- and flow-derived stresses in endothelial cell mechanobiology. Commun. Biol. 4, 764 (2021).
Tang, Y. et al. Heart-on-a-chip using human iPSC-derived cardiomyocytes with an integrated vascular endothelial layer based on a culture patch as a potential platform for drug evaluation. Biofabrication https://doi.org/10.1088/1758-5090/ac975d (2022).
Min, S. et al. Versatile human cardiac tissues engineered with perfusable heart extracellular microenvironment for biomedical applications. Nat. Commun. 15, 2564 (2024).
Ronaldson-Bouchard, K. et al. A multi-organ chip with matured tissue niches linked by vascular flow. Nat. Biomed. Eng. 6, 351–371 (2022).
Regev, A. et al. The human cell atlas. eLife 6, e27041 (2017).
Litvinukova, M. et al. Cells of the adult human heart. Nature 588, 466–472 (2020).
Mohammadi, M. H. et al. Toward hierarchical assembly of aligned cell sheets into a conical cardiac ventricle using microfabricated elastomers. Adv. Biol. 6, e2101165 (2022).
Vivas, A. et al. Generation and culture of cardiac microtissues in a microfluidic chip with a reversible open top enables electrical pacing, dynamic drug dosing and endothelial cell co-culture. Adv. Mater. Technol. 7, 2101355 (2022).
Wu, Q. et al. Automated fabrication of a scalable heart-on-a-chip device by 3D printing of thermoplastic elastomer nanocomposite and hot embossing. Bioact. Mater. 33, 46–60 (2024).
Skylar-Scott, M. A. et al. Biomanufacturing of organ-specific tissues with high cellular density and embedded vascular channels. Sci. Adv. 5, eaaw2459 (2019).
Esser, T. U. et al. Direct 3D-bioprinting of hiPSC-derived cardiomyocytes to generate functional cardiac tissues. Adv. Mater. 35, e2305911 (2023).
Choi, S. et al. Fibre-infused gel scaffolds guide cardiomyocyte alignment in 3D-printed ventricles. Nat. Mater. 22, 1039–1046 (2023).
Chang, H. et al. Recreating the heart’s helical structure-function relationship with focused rotary jet spinning. Science 377, 180–185 (2022).
Costa, P. F. et al. Mimicking arterial thrombosis in a 3D-printed microfluidic in vitro vascular model based on computed tomography angiography data. Lab Chip 17, 2785–2792 (2017).
Fenech, M. et al. Microfluidic blood vasculature replicas using backside lithography. Lab Chip 19, 2096–2106 (2019).
Zhang, R. & Larsen, N. B. Stereolithographic hydrogel printing of 3D culture chips with biofunctionalized complex 3D perfusion networks. Lab Chip 17, 4273–4282 (2017).
Heintz, K. A. et al. Fabrication of 3D biomimetic microfluidic networks in hydrogels. Adv. Healthc. Mater. 5, 2153–2160 (2016).
Wang, D. et al. Microfluidic bioprinting of tough hydrogel-based vascular conduits for functional blood vessels. Sci. Adv. 8, eabq6900 (2022).
Savoji, H. et al. 3D printing of vascular tubes using bioelastomer prepolymers by freeform reversible embedding. ACS Biomater. Sci. Eng. 6, 1333–1343 (2020).
Lai, B. F. L. et al. A well plate-based multiplexed platform for incorporation of organoids into an organ-on-a-chip system with a perfusable vasculature. Nat. Protoc. 16, 2158–2189 (2021).
Agarwal, A., Goss, J. A., Cho, A., McCain, M. L. & Parker, K. K. Microfluidic heart on a chip for higher throughput pharmacological studies. Lab Chip 13, 3599–3608 (2013).
Chramiec, A. et al. Integrated human organ-on-a-chip model for predictive studies of anti-tumor drug efficacy and cardiac safety. Lab Chip 20, 4357–4372 (2020).
Zhang, W. et al. Elastomeric free-form blood vessels for interconnecting organs on chip systems. Lab Chip 16, 1579–1586 (2016).
Zhang, B. et al. Microfabrication of AngioChip, a biodegradable polymer scaffold with microfluidic vasculature. Nat. Protoc. 13, 1793–1813 (2018).
Shin, Y. et al. Emulating endothelial dysfunction by implementing an early atherosclerotic microenvironment within a microfluidic chip. Lab Chip 19, 3664–3677 (2019).
Zhu, K. et al. Gold nanocomposite bioink for printing 3D cardiac constructs. Adv. Funct. Mater. 27, 1605352 (2017).
Buikema, J. W. et al. Wnt activation and reduced cell-cell contact synergistically induce massive expansion of functional human iPSC-derived cardiomyocytes. Cell Stem Cell 27, 50–63.e5 (2020).
Rupert, C. E. & Coulombe, K. L. K. IGF1 and NRG1 enhance proliferation, metabolic maturity, and the force-frequency response in hESC-derived engineered cardiac tissues. Stem Cell Int. 2017, 7648409 (2017).
Komosa, E. R. et al. A novel perfusion bioreactor promotes the expansion of pluripotent stem cells in a 3D-bioprinted tissue chamber. Biofabrication 16, 014101 (2023).
van Engeland, N. C. A. et al. A biomimetic microfluidic model to study signalling between endothelial and vascular smooth muscle cells under hemodynamic conditions. Lab Chip 18, 1607–1620 (2018).
Liang, Y. et al. High performance flexible organic electrochemical transistors for monitoring cardiac action potential. Adv. Healthc. Mater. 7, e1800304 (2018).
Shang, Y. et al. Cardiomyocyte-driven structural color actuation in anisotropic inverse opals. ACS Nano 13, 796–802 (2019).
Liu, H. et al. Heart-on-a-chip model with integrated extra- and intracellular bioelectronics for monitoring cardiac electrophysiology under acute hypoxia. Nano Lett. 20, 2585–2593 (2020).
Sakamiya, M., Fang, Y., Mo, X., Shen, J. & Zhang, T. A heart-on-a-chip platform for online monitoring of contractile behavior via digital image processing and piezoelectric sensing technique. Med. Eng. Phys. 75, 36–44 (2020).
Qiu, Y. et al. Microvasculature-on-a-chip for the long-term study of endothelial barrier dysfunction and microvascular obstruction in disease. Nat. Biomed. Eng. 2, 453–463 (2018).
Fuchs, S. et al. In-line analysis of organ-on-chip systems with sensors: integration, fabrication, challenges, and potential. ACS Biomater. Sci. Eng. 7, 2926–2948 (2021).
Nguyen, T. Q. & Park, W.-T. Fabrication method of multi-depth circular microchannels for investigating arterial thrombosis-on-a-chip. Sens. Actuators B Chem. 321, 128590 (2020).
Nahon, D. M. et al. Standardizing designed and emergent quantitative features in microphysiological systems. Nat. Biomed. Eng. 8, 941–962 (2024).
Aleman, J., Kilic, T., Mille, L. S., Shin, S. R. & Zhang, Y. S. Microfluidic integration of regeneratable electrochemical affinity-based biosensors for continual monitoring of organ-on-a-chip devices. Nat. Protoc. 16, 2564–2593 (2021).
Kupfer, M. E. et al. In situ expansion, differentiation, and electromechanical coupling of human cardiac muscle in a 3D bioprinted, chambered organoid. Circ. Res. 127, 207–224 (2020).
Lai, B. F. L. et al. InVADE: integrated vasculature for assessing dynamic events. Adv. Funct. Mater. 27, 1703524 (2017).
Pointon, A. et al. Cardiovascular microphysiological systems (CVMPS) for safety studies — a pharma perspective. Lab Chip 21, 458–472 (2021).
Wu, Q. et al. SARS-CoV-2 pathogenesis in an angiotensin II-induced heart-on-a-chip disease model and extracellular vesicle screening. Proc. Natl Acad. Sci. USA 121, e2403581121 (2024).
Kyriakopoulou, E. et al. Therapeutic efficacy of AAV-mediated restoration of PKP2 in arrhythmogenic cardiomyopathy. Nat. Cardiovasc. Res. 2, 1262–1276 (2023).
Gintant, G., Fermini, B., Stockbridge, N. & Strauss, D. The evolving roles of human iPSC-derived cardiomyocytes in drug safety and discovery. Cell Stem Cell 21, 14–17 (2017).