Direct hydrogel encapsulation of pluripotent stem cells enables ontomimetic differentiation and growth of engineered human heart tissues
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Human engineered heart tissues have potential to revolutionize cardiac development research, drug-testing, and treatment of heart disease; however, implementation is limited by the need to use pre-differentiated cardiomyocytes (CMs). Here we show that by providing a 3D poly(ethylene glycol)-fibrinogen hydrogel microenvironment, we can directly differentiate human pluripotent stem cells (hPSCs) into contracting heart tissues. Our straight-forward, ontomimetic approach, imitating the process of development, requires only a single cell-handling step, provides reproducible results for a range of tested geometries and size scales, and overcomes inherent limitations in cell maintenance and maturation, while achieving high yields of CMs with developmentally appropriate temporal changes in gene expression. We demonstrate that hPSCs encapsulated within this biomimetic 3D hydrogel microenvironment develop into functional cardiac tissues composed of self-aligned CMs with evidence of ultrastructural maturation, mimicking heart development, and enabling investigation of disease mechanisms and screening of compounds on developing human heart tissue.
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The sarcomeric organization of hvCOC resembled other human engineered cardiac tissue constructs and differed from random clusters.
“with sarcomeric arrangements similar to other human engineered cardiac tissue constructs [14,21–23] but distinct from random clusters.”
From Bioengineering an electro-mechanically functional miniature ventricular heart chamber from human pluripotent stem cells (2018) · cites this paper as [22]
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3D bioprinting of tissues and organs
Murphy, S. V., & Atala, A. (2014) · Nature Biotechnology · doi:10.1038/nbt.2958 · Cited by 7,034 · see citing works
Lian, X., Zhang, J., Azarin, S. M., Zhu, K., Hazeltine, L. B., Bao, X., Hsiao, C., Kamp, T. J., & Palecek, S. P. (2013) · Nature Protocols · doi:10.1038/nprot.2012.150 · Cited by 1,748 · see citing works
Lian, X., Hsiao, C., Wilson, G., Zhu, K., Hazeltine, L. B., Azarin, S. M., Raval, K. K., Zhang, J., Kamp, T. J., & Palecek, S. P. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1200250109 · Cited by 1,717 · see citing works
Chemically defined generation of human cardiomyocytes
Burridge, P. W., Matsa, E., Shukla, P., Lin, Z. C., Churko, J. M., Ebert, A. D., Lan, F., Diecke, S., Huber, B., Mordwinkin, N. M., et al. (2014) · Nature Methods · doi:10.1038/nmeth.2999 · Cited by 1,606 · see citing works
Human embryonic-stem-cell-derived cardiomyocytes regenerate non-human primate hearts
Chong, J. J. H., Yang, X., Don, C. W., Minami, E., Liu, Y.-W., Weyers, J. J., Mahoney, W. M., Biber, B. P. V., Cook, S. M., Palpant, N. J., et al. (2014) · Nature · doi:10.1038/nature13233 · Cited by 1,404 · see citing works
Laflamme, M. A., & Murry, C. E. (2011) · Nature · doi:10.1038/nature10147 · Cited by 1,231 · see citing works
Kattman, S. J., Witty, A. D., Gagliardi, M., Dubois, N. C., Niapour, M., Hotta, A., Ellis, J., & Keller, G. (2011) · Cell Stem Cell · doi:10.1016/j.stem.2010.12.008 · Cited by 1,159 · see citing works
Timing of new black box warnings and withdrawals for prescription medications
Lasser, K. E. (2002) · JAMA · doi:10.1001/jama.287.17.2215 · Cited by 1,005 · see citing works
Biowire: a platform for maturation of human pluripotent stem cell–derived cardiomyocytes
Nunes, S. S., Miklas, J. W., Liu, J., Aschar-Sobbi, R., Xiao, Y., Zhang, B., Jiang, J., Massé, S., Gagliardi, M., Hsieh, A., et al. (2013) · Nature Methods · doi:10.1038/nmeth.2524 · Cited by 952 · see citing works
Engineering Adolescence: Maturation of Human Pluripotent Stem Cell–Derived Cardiomyocytes
Yang, X., Pabon, L., & Murry, C. E. (2014) · Circulation Research · doi:10.1161/circresaha.114.300558 · Cited by 939 · see citing works
Tissue Engineering of a Differentiated Cardiac Muscle Construct
Zimmermann, W.-H., Schneiderbanger, K., Schubert, P., Didié, M., Münzel, F., Heubach, J. F., Kostin, S., Neuhuber, W. L., & Eschenhagen, T. (2002) · Circulation Research · doi:10.1161/hh0202.103644 · Cited by 917 · see citing works
Radisic, M., Park, H., Shing, H., Consi, T. R., Schöen, F. J., Langer, R., Freed, L. E., & Vunjak‐Novakovic, G. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0407817101 · Cited by 913 · see citing works
Rapid Transition of Cardiac Myocytes from Hyperplasia to Hypertrophy During Postnatal Development
Li, F. (1996) · Journal of Molecular and Cellular Cardiology · doi:10.1006/jmcc.1996.0163 · Cited by 837 · see citing works
Structural and Functional Maturation of Cardiomyocytes Derived from Human Pluripotent Stem Cells
Lundy, S. D., Zhu, W.-Z., Regnier, M., & Laflamme, M. A. (2013) · Stem Cells and Development · doi:10.1089/scd.2012.0490 · Cited by 738 · see citing works
Cardiomyocyte proliferation contributes to heart growth in young humans
Mollova, M., Bersell, K. R., Walsh, S., Savla, J. J., Das, L. T., Park, S., Silberstein, L. E., dos Remedios, C. G., Graham, D. A., Colan, S. D., et al. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1214608110 · Cited by 728 · see citing works
Using induced pluripotent stem cells to investigate cardiac phenotypes in Timothy syndrome
Yazawa, M., Hsueh, B., Jia, X., Pasca, A. M., Bernstein, J. A., Hallmayer, J., & Dolmetsch, R. E. (2011) · Nature · doi:10.1038/nature09855 · Cited by 677 · see citing works
Growth of engineered human myocardium with mechanical loading and vascular coculture
Tulloch, N. L., Muskheli, V., Razumova, M. V., Korte, F. S., Regnier, M., Hauch, K. D., Pabon, L., Reinecke, H., & Murry, C. E. (2011) · Circulation Research · doi:10.1161/circresaha.110.237206 · Cited by 666 · see citing works
Spontaneous Cardiomyocyte Differentiation From Adipose Tissue Stroma Cells
Planat‐Benard, V., Ménard, C., André, M., Pucéat, M., Ruiz, A. P., García‐Verdugo, J. M., Pénicaud, L., & Casteilla, L. (2003) · Circulation Research · doi:10.1161/01.res.0000109792.43271.47 · Cited by 649 · see citing works
Direct-write bioprinting of cell-laden methacrylated gelatin hydrogels
Bertassoni, L. E., Cardoso, J. C., Manoharan, V., Cristino, A. L., Bhise, N. S., Araujo, W. A., Zorlutuna, P., Vrana, N. E., Ghaemmaghami, A. M., Dokmeci, M. R., et al. (2014) · Biofabrication · doi:10.1088/1758-5082/6/2/024105 · Cited by 642 · see citing works
Adult Cardiac Sca-1-positive Cells Differentiate into Beating Cardiomyocytes
Matsuura, K., Nagai, T., Nishigaki, N., Oyama, T., Nishi, J., Wada, H., Sano, M., Toko, H., Akazawa, H., Sato, T., et al. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m310822200 · Cited by 638 · see citing works
Zhang, D., Shadrin, I. Y., Lam, J., Xian, H.-Q., Snodgrass, H. R., & Bursac, N. (2013) · Biomaterials · doi:10.1016/j.biomaterials.2013.04.026 · Cited by 565 · see citing works
Liang, P., Lan, F., Lee, A. S., Gong, T., Sánchez-Freire, V., Wang, Y., Diecke, S., Sallam, K., Knowles, J. W., Wang, P. J., et al. (2013) · Circulation · doi:10.1161/circulationaha.113.001883 · Cited by 535 · see citing works
Lowes, B. D., Minobe, W. A., Abraham, W. T., Rizeq, M. N., Bohlmeyer, T. J., Quaife, R. A., Roden, R. L., Dutcher, D. L., Robertson, A. D., Voelkel, N. F., et al. (1997) · Journal of Clinical Investigation · doi:10.1172/jci119770 · Cited by 496 · see citing works
Cardiomyocyte Differentiation of Human Induced Pluripotent Stem Cells
Zwi, L., Caspi, O., Arbel, G., Huber, I., Gepstein, A., Park, I.-H., & Gepstein, L. (2009) · Circulation · doi:10.1161/circulationaha.109.868885 · Cited by 451 · see citing works
Microfluidic fabrication of microengineered hydrogels and their application in tissue engineering
Chung, B. G., Lee, K. H., Khademhosseini, A., & Lee, S. (2011) · Lab on a Chip · doi:10.1039/c1lc20859d · Cited by 437 · see citing works
T-Tubule Remodeling During Transition From Hypertrophy to Heart Failure
Sheng, W., Guo, A., Chen, B., Kutschke, W. J., Xie, Y., Zimmerman, K., Weiss, R. M., Anderson, M. E., Cheng, H., & Song, L. (2010) · Circulation Research · doi:10.1161/circresaha.109.212324 · Cited by 395 · see citing works
Chronic stretch of engineered heart tissue induces hypertrophy and functional improvement
Fink, C., Ergün, S., Kralisch, D., Remmers, U., Weil, J., & Thomas Eschenhagen, A. (2000) · The FASEB Journal · doi:10.1096/fasebj.14.5.669 · Cited by 378 · see citing works
Human engineered heart tissue as a versatile tool in basic research and preclinical toxicology
Schaaf, S., Shibamiya, A., Mewe, M., Eder, A., Stöhr, A., Hirt, M. N., Rau, T., Zimmermann, W.-H., Conradi, L., Eschenhagen, T., et al. (2011) · PLoS ONE · doi:10.1371/journal.pone.0026397 · Cited by 365 · see citing works
Photopolymerization of cell-encapsulating hydrogels: Crosslinking efficiency versus cytotoxicity
Mironi‐Harpaz, I., Wang, D. Y., Venkatraman, S. S., & Seliktar, D. (2012) · Acta Biomaterialia · doi:10.1016/j.actbio.2011.12.034 · Cited by 365 · see citing works
Self-citationBeers, J. K., Gulbranson, D. R., George, N., Siniscalchi, L. I., Jones, J. M., Thomson, J. A., & Chen, G. (2012) · Nature Protocols · doi:10.1038/nprot.2012.130 · Cited by 358 · see citing works
Concise Review: Maturation Phases of Human Pluripotent Stem Cell-Derived Cardiomyocytes
Robertson, C., Tran, D., & George, S. C. (2013) · Stem Cells · doi:10.1002/stem.1331 · Cited by 354 · see citing works
Hirt, M. N., Boeddinghaus, J., Mitchell, A. N., Schaaf, S., Börnchen, C., Müller, C., Schulz, H., Hübner, N., Stenzig, J., Stoehr, A., et al. (2014) · Journal of Molecular and Cellular Cardiology · doi:10.1016/j.yjmcc.2014.05.009 · Cited by 352 · see citing works
Lei, Y.-G., & Schaffer, D. (2013) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.1309408110 · Cited by 325 · see citing works
Mann, B. K., & West, J. L. (2002) · Journal of Biomedical Materials Research · doi:10.1002/jbm.10042 · Cited by 316 · see citing works
Structural remodeling of cardiac myocytes in patients with ischemic cardiomyopathy
Gerdes, A. M., Kellerman, S. E., Moore, J. A., Muffly, K. E., Clark, L. C., Reaves, P. Y., Malec, K. B., McKeown, P. P., & Schocken, D. D. (1992) · Circulation · doi:10.1161/01.cir.86.2.426 · Cited by 307 · see citing works
Scalable expansion of human pluripotent stem cells in suspension culture
Zweigerdt, R., Olmer, R., Singh, H., Haverich, A., & Martin, U. (2011) · Nature Protocols · doi:10.1038/nprot.2011.318 · Cited by 271 · see citing works
Dikovsky, D., Bianco‐Peled, H., & Seliktar, D. (2005) · Biomaterials · doi:10.1016/j.biomaterials.2005.09.038 · Cited by 256 · see citing works
Self-citationStanton, M. M., Samitier, J., & Sánchez, S. (2015) · Lab on a Chip · doi:10.1039/c5lc90069g · Cited by 254 · see citing works
Mihic, A., Li, J., Miyagi, Y., Gagliardi, M., Li, S.-H., Zu, J., Weisel, R. D., Keller, G., & Li, R.-K. (2014) · Biomaterials · doi:10.1016/j.biomaterials.2013.12.052 · Cited by 248 · see citing works
The human adult cardiomyocyte phenotype
Bird, S. D. (2003) · Cardiovascular Research · doi:10.1016/s0008-6363(03)00253-0 · Cited by 190 · see citing works
Calcium Handling in Human Induced Pluripotent Stem Cell Derived Cardiomyocytes
Itzhaki, I., Rapoport, S., Huber, I., Mizrahi, I., Zwi‐Dantsis, L., Arbel, G., Schiller, J., & Gepstein, L. (2011) · PLoS ONE · doi:10.1371/journal.pone.0018037 · Cited by 187 · see citing works
Advancing functional engineered cardiac tissues toward a preclinical model of human myocardium
Turnbull, I. C., Karakikes, I., Serrao, G. W., Backeris, P., Lee, J., Xie, C., Senyei, G., Gordon, R. E., Li, R. A., Akar, F. G., et al. (2014) · The FASEB Journal · doi:10.1096/fj.13-228007 · Cited by 184 · see citing works
Self-citationThe effect of extracellular matrix on embryonic stem cell-derived cardiomyocytes
Baharvand, H., Azarnia, M., Parivar, K., & Ashtiani, S. K. (2005) · Journal of Molecular and Cellular Cardiology · doi:10.1016/j.yjmcc.2004.12.011 · Cited by 167 · see citing works
Cardiac remodelling as a result of pre-term birth: implications for future cardiovascular disease
Bensley, J. G., Stacy, V., Matteo, R. M. D., Harding, R., & Black, M. J. (2010) · European Heart Journal · doi:10.1093/eurheartj/ehq104 · Cited by 167 · see citing works
Scaffold-Free Human Cardiac Tissue Patch Created from Embryonic Stem Cells
Stevens, K. R., Pabon, L., Muskheli, V., & Murry, C. E. (2008) · Tissue Engineering Part A · doi:10.1089/ten.tea.2008.0151 · Cited by 164 · see citing works
Lieu, D. K., Liu, J., Siu, C.-W., McNerney, G. P., Tse, H.-F., Abu-Khalil, A., Huser, T., & Li, R. A. (2009) · Stem Cells and Development · doi:10.1089/scd.2009.0052 · Cited by 160 · see citing works
Lou, Q., Fedorov, V. V., Glukhov, A. V., Moazami, N., Fast, V. G., & Efimov, I. R. (2011) · Circulation · doi:10.1161/circulationaha.110.989707 · Cited by 148 · see citing works
Shapira‐Schweitzer, K., & Seliktar, D. (2006) · Acta Biomaterialia · doi:10.1016/j.actbio.2006.09.003 · Cited by 147 · see citing works
Self-citationDynamic suspension culture for scalable expansion of undifferentiated human pluripotent stem cells
Amit, M., Laevsky, I., Miropolski, Y., Shariki, K., Peri, M., & Itskovitz‐Eldor, J. (2011) · Nature Protocols · doi:10.1038/nprot.2011.325 · Cited by 143 · see citing works
Tiburcy, M., Didié, M., Boy, O., Christalla, P., Döker, S., Naito, H., Karikkineth, B. C., El‐Armouche, A., Grimm, M. F., Nose, M., et al. (2011) · Circulation Research · doi:10.1161/circresaha.111.251843 · Cited by 137 · see citing works
Era Of Faster FDA Drug Approval Has Also Seen Increased Black-Box Warnings And Market Withdrawals
Frank, C., Himmelstein, D. U., Woolhandler, S. J., Bor, D. H., Wolfe, S. M., Heymann, O. D., Zallman, L., & Lasser, K. E. (2014) · Health Affairs · doi:10.1377/hlthaff.2014.0122 · Cited by 131 · see citing works
Franco, C. L., Price, J., & West, J. L. (2011) · Acta Biomaterialia · doi:10.1016/j.actbio.2011.06.011 · Cited by 120 · see citing works
Induced Pluripotent Stem Cell–Derived Cardiomyocytes
Knollmann, B. C. (2013) · Circulation Research · doi:10.1161/circresaha.112.300567 · Cited by 119 · see citing works
Weng, Z., Kong, C.-W., Ren, L., Karakikes, I., Geng, L., He, J., Chow, M. Z. Y., Mok, C. F., Chan, H. Y. S., Webb, S. E., et al. (2014) · Stem Cells and Development · doi:10.1089/scd.2013.0509 · Cited by 109 · see citing works
Shapira‐Schweitzer, K., Habib, M., Gepstein, L., & Seliktar, D. (2008) · Journal of Molecular and Cellular Cardiology · doi:10.1016/j.yjmcc.2008.10.018 · Cited by 72 · see citing works
Self-citationWorkman, V. L., Dunnett, S. B., Kille, P., & Palmer, D. D. (2007) · Biomicrofluidics · doi:10.1063/1.2431860 · Cited by 70 · see citing works
Induced pluripotent stem cell–derived cardiomyocytes in studies of inherited arrhythmias
Priori, S. G., Napolitano, C., Pasquale, E. D., & Condorelli, G. (2013) · Journal of Clinical Investigation · doi:10.1172/jci62838 · Cited by 65 · see citing works
Bearzi, C., Gargioli, C., Baci, D., Fortunato, O., Shapira‐Schweitzer, K., Kossover, O., Latronico, M. V. G., Seliktar, D., Condorelli, G., & Rizzi, R. (2014) · Cell Death and Disease · doi:10.1038/cddis.2014.12 · Cited by 65 · see citing works
Self-citationDifferentiation Pathways in Human Embryonic Stem Cell‐Derived Cardiomyocytes
Lev, S., Kehat, I., & Gepstein, L. (2005) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1341.005 · Cited by 61 · see citing works
Quantitative Measurement of Ca2+ in the Sarcoplasmic Reticulum Lumen of Mammalian Skeletal Muscle
Ziman, A. P., Ward, C. W., Rodney, G. G., Lederer, W. J., & Bloch, R. J. (2010) · Biophysical Journal · doi:10.1016/j.bpj.2010.08.032 · Cited by 58 · see citing works
Scalable Passaging of Adherent Human Pluripotent Stem Cells
Nie, Y., Walsh, P., Clarke, D. L., Rowley, J. A., & Fellner, T. (2014) · PLoS ONE · doi:10.1371/journal.pone.0088012 · Cited by 51 · see citing works
Doyle, M. J., Lohr, J. L., Chapman, C. S., Koyano‐Nakagawa, N., Garry, M. G., & Garry, D. J. (2015) · Stem Cell Reviews and Reports · doi:10.1007/s12015-015-9596-6 · Cited by 42 · see citing works
Biomimetic materials design for cardiac tissue regeneration
Dunn, D. A., Hodge, A. J., & Lipke, E. A. (2013) · Wiley Interdisciplinary Reviews Nanomedicine and Nanobiotechnology · doi:10.1002/wnan.1241 · Cited by 38 · see citing works
Self-citationGraham, D. L., & Webb, G. W. (1995) · Journal of Gynecologic Surgery · doi:10.1089/gyn.1995.11.259 · Cited by 15 · see citing works
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Shadrin, I. Y., Allen, B. W., Qian, Y., Jackman, C. P., Carlson, A. L., Juhas, M. E., & Bursac, N. (2017) · Nature Communications · doi:10.1038/s41467-017-01946-x · Cited by 420 · see citing works
Kupfer, M. E., Lin, W.-H., Ravikumar, V., Qiu, K., Wang, L., Gao, L., Bhuiyan, D. B., Lenz, M., Ai, J., Mahutga, R. R., et al. (2020) · Circulation Research · doi:10.1161/circresaha.119.316155 · Cited by 329 · see citing works
Costantini, M., Testa, S., Mozetic, P., Barbetta, A., Fuoco, C., Fornetti, E., Tamiro, F., Bernardini, S., Jaroszewicz, J., Święszkowski, W., et al. (2017) · Biomaterials · doi:10.1016/j.biomaterials.2017.03.026 · Cited by 334 · see citing works
Self-citationEngineering Cardiac Muscle Tissue
Weinberger, F., Mannhardt, I., & Eschenhagen, T. (2017) · Circulation Research · doi:10.1161/circresaha.117.310738 · Cited by 225 · see citing works
Li, R. A., Keung, W., Cashman, T. J., Backeris, P. C., Johnson, B. V., Bardot, E. S., Wong, A. O. T., Chan, P. K. W., Chan, C. W. Y., & Costa, K. D. (2018) · Biomaterials · doi:10.1016/j.biomaterials.2018.02.024 · Cited by 175 · see citing works
Self-citationNext generation of heart regenerative therapies: progress and promise of cardiac tissue engineering
Tenreiro, M. F., Louro, A. F., Alves, P. M., & Serra, M. (2021) · npj Regenerative Medicine · doi:10.1038/s41536-021-00140-4 · Cited by 145 · see citing works
Koch, L., Deiwick, A., Franke, A., Schwanke, K., Haverich, A., Zweigerdt, R., & Chichkov, B. N. (2018) · Biofabrication · doi:10.1088/1758-5090/aab981 · Cited by 132 · see citing works
Branco, M. A., Cotovio, J. P., Rodrigues, C. A. V., Vaz, S. H., Fernandes, T. G., Moreira, L. M., Cabral, J. M. S., & Diogo, M. M. (2019) · Scientific Reports · doi:10.1038/s41598-019-45047-9 · Cited by 111 · see citing works
Biomaterializing the promise of cardiac tissue engineering
Pomeroy, J. E., Helfer, A., & Bursac, N. (2019) · Biotechnology Advances · doi:10.1016/j.biotechadv.2019.02.009 · Cited by 107 · see citing works
Abecasis, B., Aguiar, T., Arnault, É., Costa, R., Gomes-Alves, P., Aspegren, A., Serra, M., & Alves, P. M. (2017) · Journal of Biotechnology · doi:10.1016/j.jbiotec.2017.01.004 · Cited by 100 · see citing works
A Microvascularized Tumor-mimetic Platform for Assessing Anti-cancer Drug Efficacy
Pradhan, S., Smith, A. M., Garson, C. J., Hassani, I., Seeto, W. J., Pant, K., Arnold, R. D., Prabhakarpandian, B., & Lipke, E. A. (2018) · Scientific Reports · doi:10.1038/s41598-018-21075-9 · Cited by 97 · see citing works
Self-citationStriated muscle function, regeneration, and repair
Shadrin, I. Y., Khodabukus, A., & Bursac, N. (2016) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-016-2285-z · Cited by 95 · see citing works
PEG‐fibrinogen hydrogels for three‐dimensional breast cancer cell culture
Pradhan, S., Hassani, I., Seeto, W. J., & Lipke, E. A. (2016) · Journal of Biomedical Materials Research Part A · doi:10.1002/jbm.a.35899 · Cited by 82 · see citing works
Self-citationMayourian, J., Ceholski, D. K., Gonzalez, D. M., Cashman, T. J., Sahoo, S., Hajjar, R. J., & Costa, K. D. (2018) · Circulation Research · doi:10.1161/circresaha.117.311589 · Cited by 81 · see citing works
Self-citationZeng, C. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms241814349 · Cited by 80 · see citing works
Porous Stimuli-Responsive Self-Folding Electrospun Mats for 4D Biofabrication
Apsite, I., Stoychev, G. V., Zhang, W., Jehnichen, D., Xie, J., & Ionov, L. (2017) · Biomacromolecules · doi:10.1021/acs.biomac.7b00829 · Cited by 72 · see citing works
Fattahi, P., Rahimian, A., Slama, M. Q., Gwon, K., Gonzalez‐Suarez, A. M., Wolf, J., Baskaran, H., Duffy, C. D., Stybayeva, G., Peterson, Q. P., et al. (2021) · Scientific Reports · doi:10.1038/s41598-021-85786-2 · Cited by 69 · see citing works
Kerscher, P., Kaczmarek, J. A., Head, S. E., Ellis, M. E., Seeto, W. J., Kim, J., Bhattacharya, S., Suppiramaniam, V. D., & Lipke, E. A. (2016) · ACS Biomaterials Science & Engineering · doi:10.1021/acsbiomaterials.6b00226 · Cited by 58 · see citing works
Self-citationFinklea, F. B., Tian, Y., Kerscher, P., Seeto, W. J., Ellis, M. E., & Lipke, E. A. (2021) · Biomaterials · doi:10.1016/j.biomaterials.2021.120818 · Cited by 56 · see citing works
Self-citationKim, H. N., Habbit, N. L., Su, C., Choi, N., Ahn, E. H., Lipke, E. A., & Kim, D. (2019) · Advanced Functional Materials · doi:10.1002/adfm.201807553 · Cited by 55 · see citing works
Self-citationHuebsch, N. (2019) · Acta Biomaterialia · doi:10.1016/j.actbio.2019.05.055 · Cited by 52 · see citing works
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Kieda, J., Shakeri, A., Landau, S., Wang, E. Y., Zhao, Y., Lai, B. F., Okhovatian, S., Wang, Y., Jiang, R., & Radisic, M. (2023) · Journal of Biomedical Materials Research Part A · doi:10.1002/jbm.a.37633 · Cited by 53 · see citing works
Li, L., Chen, Y., Wang, Y., Shi, F., Nie, Y., Liu, T., & Song, K. (2019) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2019.01.123 · Cited by 50 · see citing works
Laco, F., Lam, A. T., Woo, T. L., Tong, G. J.-L., Ho, V., Soong, P. L., Grishina, E., Lin, K., Reuveny, S., & Oh, S. (2020) · Stem Cell Research & Therapy · doi:10.1186/s13287-020-01618-6 · Cited by 50 · see citing works
Ewoldt, J. K., DePalma, S. J., Jewett, M. E., Karakan, M. Ç., Lin, Y.-M., Hashemian, P. M., Gao, X., Lou, L., McLellan, M. A., Tabares, J., et al. (2024) · Nature Methods · doi:10.1038/s41592-024-02480-7 · Cited by 54 · see citing works
Biomaterials control of pluripotent stem cell fate for regenerative therapy
Pérez, R. A., Choi, S., Han, C., Kim, J., Shim, H., Leong, K. W., & Kim, H. (2016) · Progress in Materials Science · doi:10.1016/j.pmatsci.2016.05.003 · Cited by 46 · see citing works
Self-citationDroplet Microfluidics Powered Hydrogel Microparticles for Stem Cell‐Mediated Biomedical Applications
Zheng, F., Tian, R., Lu, H., Xiao, L., Shafiq, M., Uchida, S., Chen, H., & Ma, M. (2024) · Small · doi:10.1002/smll.202401400 · Cited by 44 · see citing works
Doyle, M. J., Lohr, J. L., Chapman, C. S., Koyano‐Nakagawa, N., Garry, M. G., & Garry, D. J. (2015) · Stem Cell Reviews and Reports · doi:10.1007/s12015-015-9596-6 · Cited by 42 · see citing works
Sung, T., Su, H., Ling, Q., Kumar, S. S., Chang, Y., Hsu, S.-T., & Higuchi, A. (2020) · Biomaterials · doi:10.1016/j.biomaterials.2020.120060 · Cited by 44 · see citing works
Cardiac Tissue Chips (CTCs) for Modeling Cardiovascular Disease
Rogers, A. J., Miller, J. M., Kannappan, R., & Sethu, P. (2019) · IEEE Transactions on Biomedical Engineering · doi:10.1109/tbme.2019.2905763 · Cited by 42 · see citing works
Belair, D. G., Lu, G., Waller, L. E., Gustin, J. A., Collins, N. D., & Kolaja, K. L. (2020) · Scientific Reports · doi:10.1038/s41598-020-59542-x · Cited by 39 · see citing works
McNulty, J. D., Marti-Figueroa, C. R., Seipel, F., Plantz, J. Z., Ellingham, T., Duddleston, L., Goris, S., Cox, B. L., Osswald, T. A., Turng, L., et al. (2019) · Acta Biomaterialia · doi:10.1016/j.actbio.2019.04.050 · Cited by 32 · see citing works
Expansion Culture of Human Pluripotent Stem Cells and Production of Cardiomyocytes
Le, M. N. T., & Hasegawa, K. (2019) · Bioengineering · doi:10.3390/bioengineering6020048 · Cited by 32 · see citing works
Jarrell, D. K., Vanderslice, E. J., Lennon, M. L., Lyons, A. C., VeDepo, M. C., & Jacot, J. G. (2021) · PLoS ONE · doi:10.1371/journal.pone.0239242 · Cited by 32 · see citing works
Therapeutic Cardiac Patches for Repairing the Myocardium
Streeter, B. W., & Davis, M. E. (2018) · Advances in experimental medicine and biology · doi:10.1007/5584_2018_309 · Cited by 31 · see citing works
Chang, S., Finklea, F. B., Williams, B., Hammons, H., Hodge, A., Scott, S. N., & Lipke, E. A. (2020) · Biotechnology Progress · doi:10.1002/btpr.2986 · Cited by 30 · see citing works
Self-citationPark, J. S., Yi, S. W., Kim, H. J., Kim, S. M., & Park, K. (2016) · ACS Applied Materials & Interfaces · doi:10.1021/acsami.6b08343 · Cited by 29 · see citing works
Farzaneh, Z., Najarasl, M., Abbasalizadeh, S., Vosough, M., & Baharvand, H. (2018) · Stem Cells and Development · doi:10.1089/scd.2017.0074 · Cited by 28 · see citing works
Dynamic Click Hydrogels for Xeno‐Free Culture of Induced Pluripotent Stem Cells
Arkenberg, M. R., Dimmitt, N. H., Johnson, H. C., Koehler, K. R., & Lin, C. (2020) · Advanced Biosystems · doi:10.1002/adbi.202000129 · Cited by 27 · see citing works
Tsoi, C., Deng, R., Kwok, M., Yan, B., Lee, C. B., Li, H. S., Yi, C. H., Luo, R., Leung, K. T., Chan, G., et al. (2022) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2022.714008 · Cited by 26 · see citing works
Sung, T., Liu, C., Huang, W.-L., Lee, Y.-C., Kumar, S. S., Chang, Y., Ling, Q., Hsu, S.-T., & Higuchi, A. (2019) · Biomaterials Science · doi:10.1039/c9bm00817a · Cited by 26 · see citing works
Lin, H., Du, Q., Li, Q., Wang, O., Wang, Z., Elowsky, C. G., Liu, K., Zhang, C., Chung, S., Duan, B., et al. (2018) · Biomaterials Science · doi:10.1039/c8bm01095a · Cited by 25 · see citing works
Phenotypic Variation Between Stromal Cells Differentially Impacts Engineered Cardiac Tissue Function
Hookway, T. A., Rubio, O., Mendoza-Camacho, F. N., Rains, S., Sepulveda, J. E., Joy, D. A., & McDevitt, T. C. (2019) · Tissue Engineering Part A · doi:10.1089/ten.tea.2018.0362 · Cited by 25 · see citing works
Engineering hiPSC cardiomyocyte in vitro model systems for functional and structural assessment
Roest, A. S. V., Pardon, G., Castillo, E. A., Blair, C. A., & Pruitt, B. L. (2018) · Progress in Biophysics and Molecular Biology · doi:10.1016/j.pbiomolbio.2018.12.001 · Cited by 23 · see citing works
Kang, K., Chuai, J.-B., Xie, B.-D., Li, J., Qu, H., Wu, H. K., Fang, S., Cui, J., Xiu, L.-L., Han, J., et al. (2019) · Biomaterials · doi:10.1016/j.biomaterials.2019.119574 · Cited by 24 · see citing works
Seeto, W. J., Tian, Y., Winter, R. L., Caldwell, F. J., Wooldridge, A. A., & Lipke, E. A. (2017) · Tissue Engineering Part C Methods · doi:10.1089/ten.tec.2017.0233 · Cited by 22 · see citing works
Self-citationTemporal Impact of Substrate Anisotropy on Differentiating Cardiomyocyte Alignment and Functionality
Allen, A. C. B., Barone, E., Momtahan, N., Crosby, C. O., Tu, C., Deng, W., Polansky, K., & Zoldan, J. (2019) · Tissue Engineering Part A · doi:10.1089/ten.tea.2018.0258 · Cited by 22 · see citing works
Gwon, K., Hong, H. J., Gonzalez‐Suarez, A. M., Slama, M. Q., Choi, D., Hong, J., Baskaran, H., Stybayeva, G., Peterson, Q. P., & Revzin, A. (2021) · Bioactive Materials · doi:10.1016/j.bioactmat.2021.12.008 · Cited by 19 · see citing works
Microengineered systems with iPSC-derived cardiac and hepatic cells to evaluate drug adverse effects
Dame, K., & Ribeiro, A. J. S. (2020) · Experimental Biology and Medicine · doi:10.1177/1535370220959598 · Cited by 19 · see citing works
The Effect of Scaffold Modulus on the Morphology and Remodeling of Fetal Mesenchymal Stem Cells
Rufaihah, A. J., Arularasu, S. C., Mazlan, M. D. M., Lim, K., Chong, M. S. K., Mattar, C. N. Z., Chan, J. K. Y., Kofidis, T., & Seliktar, D. (2018) · Frontiers in Physiology · doi:10.3389/fphys.2018.01555 · Cited by 17 · see citing works
Self-citationMicromechanobiology: Focusing on the Cardiac Cell–Substrate Interface
Castillo, E. A., Lane, K. V., & Pruitt, B. L. (2020) · Annual Review of Biomedical Engineering · doi:10.1146/annurev-bioeng-092019-034950 · Cited by 15 · see citing works
Engineering Myocardium for Heart Regeneration—Advancements, Considerations, and Future Directions
Jarrell, D. K., Vanderslice, E. J., VeDepo, M. C., & Jacot, J. G. (2020) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2020.586261 · Cited by 15 · see citing works
Cohen, N., Toister, E., Lati, Y., Girshengorn, M., Levin, L., Silberstein, L., Seliktar, D., & Epstein, E. (2018) · Cytotechnology · doi:10.1007/s10616-018-0204-x · Cited by 15 · see citing works
Self-citationRogers, A. J., Kannappan, R., Khalifeh, H. A., Ghazal, M. A., Miller, J. M., El-Baz, A. S., Fast, V. G., & Sethu, P. (2018) · Cells Tissues Organs · doi:10.1159/000496934 · Cited by 14 · see citing works
Development and Application of 3D Bioprinted Scaffolds Supporting Induced Pluripotent Stem Cells
Lu, D., Liu, Y., Li, W., Ma, H., Li, T., Ma, X., Mao, Y., Liang, Q., Ma, Z., & Wang, J. N. (2021) · BioMed Research International · doi:10.1155/2021/4910816 · Cited by 13 · see citing works
Emerging Strategies for Stem Cell Lineage Commitment in Tissue Engineering and Regenerative Medicine
Ort, C., Dayekh, K., Xing, M. M. Q., & Mequanint, K. (2018) · ACS Biomaterials Science & Engineering · doi:10.1021/acsbiomaterials.8b00532 · Cited by 13 · see citing works
Koc, A., Goktas, S. S., Çağlar, T. A., & Çağavi, E. (2021) · Experimental Cell Research · doi:10.1016/j.yexcr.2021.112599 · Cited by 13 · see citing works
Komosa, E. R., Lin, W., Mahadik, B. P., Bazzi, M. S., Townsend, D., Fisher, J. P., & Ogle, B. M. (2023) · Biofabrication · doi:10.1088/1758-5090/ad084a · Cited by 13 · see citing works
Hashemi, M., Finklea, F. B., Hammons, H., Tian, Y., Young, N., Kim, E., Halloin, C., Triebert, W., Zweigerdt, R., Mitra, A., et al. (2024) · Bioactive Materials · doi:10.1016/j.bioactmat.2024.08.043 · Cited by 12 · see citing works
Self-citationHamami, R., Yameen, H. S., Gargioli, C., & Seliktar, D. (2022) · Regenerative Engineering and Translational Medicine · doi:10.1007/s40883-022-00261-2 · Cited by 10 · see citing works
Self-citationMimicking megakaryopoiesis in vitro using biomaterials: Recent advances and future opportunities
Ingavle, G. C., Shabrani, N. C., Vaidya, A., & Kale, V. P. (2019) · Acta Biomaterialia · doi:10.1016/j.actbio.2019.07.025 · Cited by 10 · see citing works
Modeling the Response of Heart Muscle to Mechanical Stimulation In Vitro
Guo, J., & Huebsch, N. (2020) · Current Tissue Microenvironment Reports · doi:10.1007/s43152-020-00007-8 · Cited by 10 · see citing works
Florido, M. H. C., & Ziats, N. P. (2024) · Journal of Biomedical Materials Research Part A · doi:10.1002/jbm.a.37669 · Cited by 9 · see citing works
Rewiring the Spine—Cutting-Edge Stem Cell Therapies for Spinal Cord Repair
Riza, Y. M., & Alzahrani, F. A. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26115048 · Cited by 10 · see citing works
Torizal, F. G., Horiguchi, I., & Sakai, Y. (2019) · The Open Biomedical Engineering Journal · doi:10.2174/1874120701913010041 · Cited by 9 · see citing works
Ellis, M. E., Harris, B. N., Hashemi, M., Harvell, B. J., Bush, M. Z., Hicks, E. E., Finklea, F. B., Wang, E. M., Nataraj, R., Young, N. P., et al. (2022) · Tissue Engineering Part A · doi:10.1089/ten.tea.2022.0107 · Cited by 8 · see citing works
Self-citationZhang, R., Guo, T., Han, Y., Huang, H., Shi, J., Hu, J., Li, H., Wang, J., Saleem, A., Zhou, P., et al. (2020) · Journal of Biomedical Materials Research Part B Applied Biomaterials · doi:10.1002/jbm.b.34759 · Cited by 8 · see citing works
Differentiating Engineered Tissue Images and Experimental Factors to Classify Cardiomyocyte Content
Mohammadi, S., Hashemi, M., Finklea, F. B., Lipke, E. A., & Cremaschi, S. (2022) · Tissue Engineering Part A · doi:10.1089/ten.tea.2022.0122 · Cited by 7 · see citing works
Self-citationPhotopolymerizable Materials for Cell Encapsulation
Tytgat, L., Baudis, S., Ottevaere, H., Liska, R., Hugo Thienpont, A., Dubruel, P., & Vlierberghe, S. V. (2018) · Springer eBooks · doi:10.1007/978-3-319-45444-3_15 · Cited by 7 · see citing works
Finklea, F. B., Hashemi, M., Tian, Y., Hammons, H., Halloin, C., Triebert, W., Zweigerdt, R., & Lipke, E. A. (2024) · Biotechnology and Bioengineering · doi:10.1002/bit.28818 · Cited by 6 · see citing works
Self-citationYang, J., Yue, T., He, J. X., Xiong, S., Luo, Y., & Hou, J. (2025) · Frontiers in Pharmacology · doi:10.3389/fphar.2025.1600604 · Cited by 5 · see citing works
Mohammadi, S., Hashemi, M., Finklea, F. B., Williams, B., Lipke, E. A., & Cremaschi, S. (2022) · Journal of Advanced Manufacturing and Processing · doi:10.1002/amp2.10148 · Cited by 5 · see citing works
Self-citationRadhakrishnan, H. R. G., Chithamparam, P., Thiagamani, S. M. K., Muthukumaran, A., & Ayrılmış, N. (2025) · Polymers for Advanced Technologies · doi:10.1002/pat.70280 · Cited by 4 · see citing works
Multidisciplinary Approaches in the Treatment of Retinal Degenerative Diseases: A Review
Chen, J., Zhuo, X., Zhu, Y., & Zhuo, Y. (2023) · Advanced Therapeutics · doi:10.1002/adtp.202300162 · Cited by 4 · see citing works
A Bionic Testbed for Cardiac Ablation Tools
Lin, W., Zhu, Z., Ravikumar, V., Sharma, V., Tolkacheva, E. G., McAlpine, M. C., & Ogle, B. M. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms232214444 · Cited by 4 · see citing works
Photopolymerizable Materials for Cell Encapsulation
Tytgat, L., Baudis, S., Ottevaere, H., Liska, R., Hugo Thienpont, A., Dubruel, P., & Vlierberghe, S. V. (2017) · Springer eBooks · doi:10.1007/978-3-319-40498-1_15-1 · Cited by 4 · see citing works
Yang, D. M., Hu, Y., Liu, S., Yang, W., Ren, X., Li, Y., Xu, F., Gong, M., Zhao, Y., Qiu, X., et al. (2025) · Chem · doi:10.1016/j.chempr.2025.102596 · Cited by 3 · see citing works
Banerjee, A., Dalsania, K., Damian, J., Asuncion, J., Masoumi, A., & Noshadi, I. (2026) · Acta Biomaterialia · doi:10.1016/j.actbio.2026.01.018 · Cited by 4 · see citing works
Hunt, N. C., & Lako, M. (2016) · Regenerative Medicine · doi:10.2217/rme-2016-0095 · Cited by 3 · see citing works
Hydrogel sensing platforms for monitoring contractility in in vitro cardiac models
Lu, J., Pan, X., Zhang, W., Han, J., Chen, J., Song, M., Xu, C., Li, X., Wang, J., & Wang, L. (2025) · Nanoscale · doi:10.1039/d4nr04087b · Cited by 3 · see citing works
Biomaterial platforms in cardiovascular regenerative medicine – challenges and future perspectives
Vo, Q. D. (2025) · Regenerative Medicine · doi:10.1080/17460751.2025.2601482 · Cited by 1 · see citing works
Sidorov, V. Y., Sidorova, T. N., Samson, P. C., Reiserer, R. S., Britt, C. M., Neely, M. D., Ess, K. C., & Wikswo, J. P. (2024) · Bioengineering · doi:10.3390/bioengineering11030234 · Cited by 1 · see citing works
Sacralizaciones artísticas en los autos sacramentales de Lope. El caso de La puente del mundo
Baztán, J. M. E. (2018) · Revista de Literatura · doi:10.3989/revliteratura.2018.02.022 · Cited by 1 · see citing works
Development of bio-inks for bioprinting applications
Ribeiro, R. D. C. (2019) · Cited by 1 · see citing works
Murphy, J. F., Costa, K. D., & Turnbull, I. C. (2023) · Computer Methods and Programs in Biomedicine Update · doi:10.1016/j.cmpbup.2023.100107
Self-citationLaco, F., Lam, A. T., Woo, T.-L., Tong, G. J.-L., Ho, V., Soong, P. L., Grishina, E., Lin, K.-H., Reuveny, S., & Oh, S. K.-W. (2020) · Figshare · doi:10.6084/m9.figshare.11998386
Qiao, L., Xu, Y., Wang, X., Zhu, Y. C., Zhang, T., Niu, Y., Chen, M., Yang, S., & Liang, G. (2026) · Stem Cell Research & Therapy · doi:10.1186/s13287-026-05114-1
- Authors
- Kerscher, P., Turnbull, I. C., Hodge, A. J., Kim, J., Seliktar, D., Easley, C. J., Costa, K. D., & Lipke, E. A.
- Affiliations
- Auburn University (US)
- Icahn School of Medicine at Mount Sinai (US)
- Technion – Israel Institute of Technology (IL)
- Corresponding author
- Lipke, Elizabeth A.
- Venue
- Biomaterials
- Publisher
- Elsevier BV
- Published
- 2016-03
- Volume
- 83
- Pages
- 383-395
- ISSN
- 0142-9612 (ISSN-L)
- PMC
- PMC4804626
- OpenAlex
- W2215717357
- Cited by
- 88
- References
- 64
- Citations by year
- 2026: 2 · 2025: 6 · 2024: 6 · 2023: 5 · 2022: 6 · 2021: 7 · 2020: 13 · 2019: 15 · 2018: 14 · 2017: 7 · 2016: 6 · 2015: 1
- FWCI
- 4.05
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (am, 332 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Biomaterials (acceptedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Science Foundation (CBET-1150854, CBET-1403495)
- US National Institutes of Health
- NIH/NHLBI Program of Excellence in Nanotechnology (PEN) Award (HHSN268201000045C, R01DK093810)
- American Heart Association pre-doctoral fellowship (13PRE1470078)
- AL-EPSCoR GRSP
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Medicine › Hydrogels: synthesis, properties, applications
- Keywords
- pluripotent stem cells, engineered heart tissue, cardiomyocyte differentiation, hydrogel encapsulation, 3D microenvironment, heart development, cardiomyocyte maturation, self-alignment, cardiac disease modeling, drug screening
- MeSH terms
- Cell Differentiation, Cell Survival, Gene Expression Regulation, Heart, Humans, Polyethylene Glycols, Cells, Immobilized, Hydrogel, Polyethylene Glycol Dimethacrylate, Tissue Engineering, Myocytes, Cardiac, Pluripotent Stem Cells, Cell Proliferation
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