Direct 3D‐Bioprinting of hiPSC‐Derived Cardiomyocytes to Generate Functional Cardiac Tissues
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Abstract
3D-bioprinting is a promising technology to produce human tissues as drug screening tool or for organ repair. However, direct printing of living cells has proven difficult. Here, a method is presented to directly 3D-bioprint human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes embedded in a collagen-hyaluronic acid ink, generating centimeter-sized functional ring- and ventricle-shaped cardiac tissues in an accurate and reproducible manner. The printed tissues contain hiPSC-derived cardiomyocytes with well-organized sarcomeres and exhibit spontaneous and regular contractions, which persist for several months and are able to contract against passive resistance. Importantly, beating frequencies of the printed cardiac tissues can be modulated by pharmacological stimulation. This approach opens up new possibilities for generating complex functional cardiac tissues as models for advanced drug screening or as tissue grafts for organ repair or replacement.
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More sophisticated fabrication strategies, including nanofabrication and 3D (bio)printing, offer greater control over geometry and microstructure but raise concerns about efficiency, cost, and throughput.
“More sophisticated fabrication strategies, including nanofabrication and 3D (bio)printing, offer greater control over geometry and microstructure but raise concerns about efficiency, cost, and throughput (Lee et al., 2019; Kupfer et al., 2020; Esser et al., 2023).”
From Mini-hearts for disease modeling and drug testing – process optimization versus biological functionality (2026) · cites this paper as Esser et al., 2023
The section 'Simple method to produce a support bath for in-gel printing' (page not provided) reports that printed constructs accurately reproduced 3D models, supporting the claim about geometric control. The Discussion (page not provided) also describes the potential to place different cardiomyocyte subtypes precisely. The paper does not substantiate the attributed concerns about efficiency, cost, or throughput, or address nanofabrication. (LLM, conf=0.86)
Experimental — accuracy not yet measuredSome complex engineered cardiac chambers lack functional readouts, limiting their use for drug testing and disease modeling.
“Some of these more complex engineered cardiac chambers lack functional readouts, thus, limiting their use for drug testing and disease modeling (Esser et al., 2023; Xie et al., 2023; Lee et al., 2019).”
From Mini-hearts for disease modeling and drug testing – process optimization versus biological functionality (2026) · cites this paper as Esser et al., 2023
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Cites
Fiji: an open-source platform for biological-image analysis
Schindelin, J., Arganda-Carreras, I., Frise, E., Kaynig, V., Longair, M., Pietzsch, T., Preibisch, S., Rueden, C., Saalfeld, S., Schmid, B., et al. (2012) · Nature Methods · doi:10.1038/nmeth.2019 · Cited by 66,890 · see citing works
Global Burden of Cardiovascular Diseases and Risk Factors, 1990–2019
Roth, G. A., Mensah, G. A., Johnson, C. O., Addolorato, G., Ammirati, E., Baddour, L. M., Barengo, N. C., Beaton, A. Z., Benjamin, E. J., Benziger, C. P., et al. (2020) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2020.11.010 · Cited by 11,449 · see citing works
Hinton, T. J., Jallerat, Q., Palchesko, R. N., Park, J. H., Grodzicki, M. S., Shue, H.-J., Ramadan, M. H., Hudson, A. R., & Feinberg, A. W. (2015) · Science Advances · doi:10.1126/sciadv.1500758 · Cited by 1,805 · see citing works
3D bioprinting of collagen to rebuild components of the human heart
Lee, A., Hudson, A. R., Shiwarski, D. J., Tashman, J. W., Hinton, T. J., Yerneni, S., Bliley, J. M., Campbell, P. G., & Feinberg, A. W. (2019) · Science · doi:10.1126/science.aav9051 · Cited by 1,782 · 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
Advanced maturation of human cardiac tissue grown from pluripotent stem cells
Ronaldson-Bouchard, K., Ma, S. P., Yeager, K., Chen, T., Song, L., Sirabella, D., Morikawa, K., Teles, D., Yazawa, M., & Vunjak-Novakovic, G. (2018) · Nature · doi:10.1038/s41586-018-0016-3 · Cited by 1,272 · see citing works
Dynamics of Cell Generation and Turnover in the Human Heart
Bergmann, O., Zdunek, S., Felker, A., Salehpour, M., Alkass, K., Bernard, S., Sjostrom, S. L., Szewczykowska, M., Jackowska, T., dos Remedios, C. G., et al. (2015) · Cell · doi:10.1016/j.cell.2015.05.026 · Cited by 1,133 · see citing works
3D Printing of Personalized Thick and Perfusable Cardiac Patches and Hearts
Noor, N., Shapira, A., Edri, R., Gal, I., Wertheim, L., & Dvir, T. (2019) · Advanced Science · doi:10.1002/advs.201900344 · Cited by 1,042 · see citing works
Schuurman, W., Levett, P. A., Pot, M. W., van Weeren, P. R., Dhert, W. J. A., Hutmacher, D. W., Melchels, F. P. W., Klein, T. J., & Malda, J. (2013) · Macromolecular Bioscience · doi:10.1002/mabi.201200471 · Cited by 791 · see citing works
Tiburcy, M., Hudson, J. E., Balfanz, P., Schlick, S. F., Meyer, T., Liao, M.-L. C., Levent, E., Raad, F. S., Zeidler, S., Wingender, E., et al. (2017) · Circulation · doi:10.1161/circulationaha.116.024145 · Cited by 650 · see citing works
Kawamura, M., Miyagawa, S., Miki, K., Saito, A., Fukushima, S., Higuchi, T., Kawamura, T., Kuratani, T., Daimon, T., Shimizu, T., et al. (2012) · Circulation · doi:10.1161/circulationaha.111.084343 · Cited by 493 · see citing works
From Shape to Function: The Next Step in Bioprinting
Levato, R., Jüngst, T., Scheuring, R. G., Blunk, T., Gröll, J., & Malda, J. (2020) · Advanced Materials · doi:10.1002/adma.201906423 · Cited by 480 · see citing works
Mills, R. J., Titmarsh, D. M., Koenig, X., Parker, B. L., Ryall, J. G., Quaife-Ryan, G. A., Voges, H. K., Hodson, M. P., Ferguson, C., Drowley, L., et al. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1707316114 · Cited by 478 · see citing works
Gao, L., Gregorich, Z. R., Zhu, W., Mattapally, S., Oduk, Y., Lou, X., Kannappan, R., Borovjagin, A. V., Walcott, G. P., Pollard, A. E., et al. (2017) · Circulation · doi:10.1161/circulationaha.117.030785 · Cited by 465 · see citing works
Sun, W., Starly, B., Daly, A. C., Burdick, J. A., Groll, J., Skeldon, G., Shu, W., Sakai, Y., Shinohara, M., Nishikawa, M., et al. (2020) · Biofabrication · doi:10.1088/1758-5090/ab5158 · Cited by 426 · see citing works
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
Metabolic Maturation Media Improve Physiological Function of Human iPSC-Derived Cardiomyocytes
Feyen, D. A. M., McKeithan, W. L., Bruyneel, A. A. N., Spiering, S., Hörmann, L., Ulmer, B., Zhang, H., Briganti, F., Schweizer, M., Hegyi, B., et al. (2020) · Cell Reports · doi:10.1016/j.celrep.2020.107925 · Cited by 400 · see citing works
Human Engineered Heart Tissue: Analysis of Contractile Force
Mannhardt, I., Breckwoldt, K., Letuffe-Brenière, D., Schaaf, S., Schulz, H., Neuber, C., Benzin, A., Werner, T., Eder, A., Schulze, T., et al. (2016) · Stem Cell Reports · doi:10.1016/j.stemcr.2016.04.011 · Cited by 398 · see citing works
BigStitcher: reconstructing high-resolution image datasets of cleared and expanded samples
Hörl, D., Rusak, F. R., Preußer, F., Tillberg, P. W., Randel, N., Chhetri, R. K., Cardona, A., Keller, P., Harz, H., Leonhardt, H., et al. (2019) · Nature Methods · doi:10.1038/s41592-019-0501-0 · Cited by 387 · see citing works
Grüneboom, A., Hasenberg, A., Ludwig‐Portugall, I., Medyukhina, A., Männ, L., Brenzel, A., Engel, D. R., Figge, M. T., Kurts, C., & Gunzer, M. (2016) · Journal of the American Society of Nephrology · doi:10.1681/asn.2016020232 · Cited by 348 · 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
Human Engineered Heart Muscles Engraft and Survive Long Term in a Rodent Myocardial Infarction Model
Riegler, J., Tiburcy, M., Ebert, A., Tzatzalos, E., Raaz, U., Abilez, O. J., Shen, Q., Kooreman, N. G., Neofytou, E. A., Chen, V. C., et al. (2015) · Circulation Research · doi:10.1161/circresaha.115.306985 · Cited by 255 · see citing works
A tissue-engineered scale model of the heart ventricle
MacQueen, L. A., Sheehy, S. P., Chantre, C. O., Zimmerman, J. F., Pasqualini, F. S., Liu, X., Goss, J. A., Campbell, P. H., Gonzalez, G. M., Park, S.-J., et al. (2018) · Nature Biomedical Engineering · doi:10.1038/s41551-018-0271-5 · Cited by 227 · see citing works
Engineering Cardiac Muscle Tissue
Weinberger, F., Mannhardt, I., & Eschenhagen, T. (2017) · Circulation Research · doi:10.1161/circresaha.117.310738 · Cited by 225 · see citing works
Buikema, J. W., Lee, S., Goodyer, W. R., Maas, R. G. C., Chirikian, O., Li, G., Miao, Y., Paige, S. L., Lee, D. C., Wu, H., et al. (2020) · Cell stem cell · doi:10.1016/j.stem.2020.06.001 · Cited by 218 · see citing works
Fibre-infused gel scaffolds guide cardiomyocyte alignment in 3D-printed ventricles
Choi, S., Lee, K. Y., Kim, S. L., MacQueen, L. A., Chang, H., Zimmerman, J. F., Jin, Q., Peters, M. M., Ardoña, H. A. M., Liu, X., et al. (2023) · Nature Materials · doi:10.1038/s41563-023-01611-3 · Cited by 212 · see citing works
Roshanbinfar, K., Vogt, L., Greber, B., Diecke, S., Boccaccini, A. R., Scheibel, T., & Engel, F. B. (2018) · Advanced Functional Materials · doi:10.1002/adfm.201803951 · Cited by 193 · see citing works
Self-citationHasenfuss, G. P., Mulieri, L. A., Blanchard, E. M., Holubarsch, C., Leavitt, B. J., Ittleman, F. P., & Alpert, N. R. (1991) · Circulation Research · doi:10.1161/01.res.68.3.836 · Cited by 185 · 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
Fang, Y., Guo, Y., Wu, B., Liu, Z., Ye, M., Xu, Y., Ji, M., Chen, L., Lu, B., Nie, K., et al. (2023) · Advanced Materials · doi:10.1002/adma.202205082 · Cited by 155 · see citing works
Bacterial infection imaging with [ 18 F]fluoropropyl-trimethoprim
Sellmyer, M. A., Lee, I., Hou, C., et al. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1703109114 · Cited by 144 · see citing works
Thrombopoiesis is spatially regulated by the bone marrow vasculature
Stegner, D., vanEeuwijk, J. M. M., Angay, O., et al. (2017) · Nature Communications · doi:10.1038/s41467-017-00201-7 · Cited by 143 · see citing works
Human Engineered Heart Tissue Patches Remuscularize the Injured Heart in a Dose-Dependent Manner
Querdel, E., Reinsch, M. C., Castro, L., Köse, D., Bähr, A., Reich, S., Geertz, B., Ulmer, B. M., Schulze, M. L., Lemoine, M. D., et al. (2021) · Circulation · doi:10.1161/circulationaha.120.047904 · Cited by 136 · see citing works
Recreating the heart's helical structure-function relationship with focused rotary jet spinning
Chang, H., Liu, Q., Zimmerman, J. F., Lee, K. Y., Jin, Q., Peters, M. M., Rosnach, M., Choi, S., Kim, S. L., Ardoña, H. A. M., et al. (2022) · Science · doi:10.1126/science.abl6395 · Cited by 131 · see citing works
Quantification of decellularized human myocardial matrix: A comparison of six patients
Johnson, T. D., Hill, R. C., Dzieciątkowska, M., Nigam, V., Behfar, A., Christman, K. L., & Hansen, K. C. (2015) · PROTEOMICS - CLINICAL APPLICATIONS · doi:10.1002/prca.201500048 · Cited by 126 · see citing works
Roshanbinfar, K., Mohammadi, Z., Mesgar, A. S.-M., Dehghan, M. M., Oommen, O. P., Hilborn, J. G., & Engel, F. B. (2019) · Biomaterials Science · doi:10.1039/c9bm00434c · Cited by 115 · see citing works
Self-citation3D Tissue and Organ Printing—Hope and Reality
Shapira, A., & Dvir, T. (2021) · Advanced Science · doi:10.1002/advs.202003751 · Cited by 112 · see citing works
Bertassoni, L. E. (2021) · Advanced Materials · doi:10.1002/adma.202101321 · Cited by 96 · see citing works
Comparison of 10 Control hPSC Lines for Drug Screening in an Engineered Heart Tissue Format
Mannhardt, I., Saleem, U., Mosqueira, D., Loos, M., Ulmer, B. M., Lemoine, M. D., Larsson, C., Améen, C., de Korte, T., Vlaming, M. L. H., et al. (2020) · Stem Cell Reports · doi:10.1016/j.stemcr.2020.09.002 · Cited by 74 · see citing works
Cámara-Torres, M., Sinha, R., Mota, C., et al. (2019) · Acta Biomaterialia · doi:10.1016/j.actbio.2019.11.020 · Cited by 68 · see citing works
Roshanbinfar, K., Koleśnik-Gray, M. M., Angeloni, M., Schrüfer, S., Fiedler, M., Schubert, D. W., Ferrazzi, F., Krstić, V., & Engel, F. B. (2023) · Advanced Healthcare Materials · doi:10.1002/adhm.202202408 · Cited by 64 · see citing works
Self-citationContractile Force of Transplanted Cardiomyocytes Actively Supports Heart Function After Injury
Stüdemann, T., Rössinger, J., Manthey, C., Geertz, B., Srikantharajah, R., von Bibra, C., Shibamiya, A., Köhne, M., Wiehler, A., Wiegert, J. S., et al. (2022) · Circulation · doi:10.1161/circulationaha.122.060124 · Cited by 50 · see citing works
Cardiac Subtype-Specific Modeling of Kv1.5 Ion Channel Deficiency Using Human Pluripotent Stem Cells
Marczenke, M., Piccini, I., Mengarelli, I., Fell, J., Röpke, A., Seebohm, G., Verkerk, A. O., & Greber, B. (2017) · Frontiers in Physiology · doi:10.3389/fphys.2017.00469 · Cited by 46 · see citing works
Frankowski, J., Kurzątkowska, M., Sobczak, M., & Piotrowska, U. (2023) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2023.123313 · Cited by 44 · see citing works
Post‐Maturation Reinforcement of 3D‐Printed Vascularized Cardiac Tissues
Silberman, E., Oved, H., Namestnikov, M., Shapira, A., & Dvir, T. (2023) · Advanced Materials · doi:10.1002/adma.202302229 · Cited by 37 · see citing works
Xie, Z., Zeng, J., Kang, D., Saito, S., Miyagawa, S., Sawa, Y., & Matsusaki, M. (2023) · Advanced Healthcare Materials · doi:10.1002/adhm.202301090 · Cited by 31 · see citing works
CHIR99021 Promotes hiPSC‐Derived Cardiomyocyte Proliferation in Engineered 3D Microtissues
Hesselbarth, R., Esser, T. U., Roshanbinfar, K., Schrüfer, S., Schubert, D. W., & Engel, F. B. (2021) · Advanced Healthcare Materials · doi:10.1002/adhm.202100926 · Cited by 26 · see citing works
Self-citationStem Cells and Their Cardiac Derivatives for Cardiac Tissue Engineering and Regenerative Medicine
Roshanbinfar, K., Esser, T. U., & Engel, F. B. (2020) · Antioxidants and Redox Signaling · doi:10.1089/ars.2020.8193 · Cited by 24 · see citing works
Self-citationSpörrer, M., Kah, D., Gerum, R. C., Reischl, B., Huraskin, D., Dessalles, C. A., Schneider, W., Goldmann, W. H., Herrmann, H. O., Thievessen, I., et al. (2021) · Neuropathology and Applied Neurobiology · doi:10.1111/nan.12784 · Cited by 16 · see citing works
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Advancements in tissue engineering for cardiovascular health: a biomedical engineering perspective
Razavi, Z.-S., Soltani, M., Mahmoudvand, G., Farokhi, S., Karimi-Rouzbahani, A., Farasati-Far, B., Tahmasebi-Ghorabi, S., Pazoki-Toroudi, H., & Afkhami, H. (2024) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2024.1385124 · Cited by 64 · see citing works
Li, G., He, J., Shi, J., Li, X., Liu, L., Ge, X., Chen, W., Jia, J., Wang, J., Yin, M., et al. (2025) · Gut · doi:10.1136/gutjnl-2024-333885 · Cited by 41 · see citing works
Hecking, J., Cano-Jorge, M., Passier, R., & Rivera-Arbeláez, J. M. (2026) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2025.1719533
- Authors
- Esser, T. U., Anspach, A., Muenzebrock, K. A., Kah, D., Schrüfer, S., Schenk, J., Heinze, K. G., Schubert, D. W., Fabry, B., & Engel, F. B.
- Affiliations
- Friedrich-Alexander-Universität Erlangen-Nürnberg (DE)
- University of Würzburg (DE)
- Corresponding author
- Engel, Felix B.
- ORCID
- Venue
- Advanced Materials
- Publisher
- Wiley
- Published
- 2023-11-20
- Volume
- 35
- Issue
- 52
- Pages
- e2305911-e2305911
- ISSN
- 0935-9648 (ISSN-L)
- 1521-4095
- OpenAlex
- W4386347405
- Cited by
- 75
- References
- 49
- Citations by year
- 2026: 25 · 2025: 28 · 2024: 22
- FWCI
- 5.91
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Advanced Materials (publishedVersion, cc-by-nc-nd)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- Deutsche Forschungsgemeinschaft (INST410/91‐1 FUGG, 326998133 – TRR 225)
- Topics
- Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
- Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Keywords
- 3D bioprinting, hiPSC-derived cardiomyocytes, sarcomere organization, spontaneous contractions, drug screening, tissue grafts, organ restoration
- MeSH terms
- Humans, Tissue Engineering, Myocytes, Cardiac, Induced Pluripotent Stem Cells, Bioprinting, Printing, Three-Dimensional
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