Engineering the cardiac tissue microenvironment
Open accessAbstract
In this article we review the microfabrication approaches, with a focus on bioprinting and organ-on-chip technologies, used to engineer cardiac tissue. First, we give a brief introduction to heart anatomy and physiology, and the developmental stages of the heart from fetal stages to adulthood. We also give information on the cardiac tissue microenvironment, including the cells residing in the heart, the biochemical composition and structural organization of the heart extracellular matrix, the signaling factors playing roles in heart development and maturation, and their interactions with one another. We then give a brief summary of both cardiovascular diseases and the current treatment methods used in the clinic to treat these diseases. Second, we explain how tissue engineering recapitulates the development and maturation of the normal or diseased heart microenvironment by spatially and temporally incorporating cultured cells, biomaterials, and growth factors (GF). We briefly expand on the cells, biomaterials, and GFs used to engineer the heart, and the limitations of their use. Next, we review the state-of-the-art tissue engineering approaches, with a special focus on bioprinting and heart-on-chip technologies, intended to (i) treat or replace the injured cardiac tissue, and (ii) create cardiac disease models to study the basic biology of heart diseases, develop drugs against these diseases, and create diagnostic tools to detect heart diseases. Third, we discuss the recent trends in cardiac tissue engineering, including the use of machine learning, CRISPR/Cas editing, exosomes and microRNAs, and immune modeling in engineering the heart. Finally, we conclude our article with a brief discussion on the limitations of cardiac tissue engineering and our suggestions to engineer more reliable and clinically relevant cardiac tissues.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Engineered three-dimensional cardiac systems, including organoids, engineered heart tissues, and heart-on-chip platforms, provide structural and functional insights into cardiac biology.
“Engineered three-dimensional cardiac systems - including organoids, engineered heart tissues, and heart-on-chip platforms offer promising alternatives, providing structural and functional insights into cardiac biology.”
From Mini-hearts for disease modeling and drug testing – process optimization versus biological functionality (2026) · cites this paper as Ronan et al., 2023
Cites
Ezetimibe Added to Statin Therapy after Acute Coronary Syndromes
Cannon, C. P., Blazing, M. A., Giugliano, R. P., McCagg, A., White, J. A., Theroux, P., Darius, H., Lewis, B. S., Ophuis, T. O., Jukema, J. W., et al. (2015) · New England Journal of Medicine · doi:10.1056/nejmoa1410489 · Cited by 4,487 · see citing works
The intersection between aging and cardiovascular disease
North, B. J., & Sinclair, D. A. (2012) · Circulation Research · doi:10.1161/circresaha.111.246876 · Cited by 1,585 · 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
Effects of stress on the development and progression of cardiovascular disease
Kivimäki, M., & Steptoe, A. (2018) · Nature Reviews Cardiology · doi:10.1038/nrcardio.2017.189 · Cited by 1,197 · see citing works
Functional screening identifies miRNAs inducing cardiac regeneration
Eulalio, A., Mano, M., Ferro, M. D., Zentilin, L., Sinagra, G., Zacchigna, S., & Giacca, M. (2012) · Nature · doi:10.1038/nature11739 · Cited by 1,029 · see citing works
Macrophages Facilitate Electrical Conduction in the Heart
Hulsmans, M., Clauss, S., Xiao, L., Aguirre, A. D., King, K. R., Hanley, A., Hucker, W. J., Wülfers, E. M., Seemann, G., Courties, G., et al. (2017) · Cell · doi:10.1016/j.cell.2017.03.050 · Cited by 1,011 · 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
Allogeneic transplantation of iPS cell-derived cardiomyocytes regenerates primate hearts
Shiba, Y., Gomibuchi, T., Seto, T., Wada, Y., Ichimura, H., Tanaka, Y., Ogasawara, T., Okada, K., Shiba, N., Sakamoto, K., et al. (2016) · Nature · doi:10.1038/nature19815 · Cited by 840 · see citing works
Exosome engineering: Current progress in cargo loading and targeted delivery
Fu, S., Wang, Y., Xia, X., & Zheng, J. C. (2020) · NanoImpact · doi:10.1016/j.impact.2020.100261 · Cited by 444 · see citing works
Three-dimensional transmural organization of perimysial collagen in the heart
Pope, A. J., Sands, G. B., Smaill, B. H., & LeGrice, I. J. (2008) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00484.2008 · Cited by 205 · see citing works
Zhang, J., Tao, R., Campbell, K. F., Carvalho, J. L., Ruiz, E. C., Kim, G. C., Schmuck, E. G., Raval, A. N., da Rocha, A. M., Herron, T. J., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-09831-5 · Cited by 201 · see citing works
Challenges and opportunities for the next generation of cardiovascular tissue engineering
Cho, S., Discher, D. E., Leong, K. W., Vunjak-Novakovic, G., & Wu, J. C. (2022) · Nature Methods · doi:10.1038/s41592-022-01591-3 · Cited by 176 · see citing works
Cardiovascular organ-on-a-chip platforms for drug discovery and development
Ribas, J., Sadeghi, H., Manbachi, A., Leijten, J., Brinegar, K., Zhang, Y. S., Ferreira, L., & Khademhosseini, A. (2016) · Applied In Vitro Toxicology · doi:10.1089/aivt.2016.0002 · Cited by 161 · see citing works
Das, S., Kim, S.-W., Choi, Y.-J., Lee, S., Lee, S.-H., Kong, J.-S., Park, H.-J., Cho, D.-W., & Jang, J. (2019) · Acta Biomaterialia · doi:10.1016/j.actbio.2019.04.026 · Cited by 150 · 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
Matrix-bound nanovesicles recapitulate extracellular matrix effects on macrophage phenotype
Huleihel, L., Bartolacci, J. G., Dziki, J. L., Vorobyov, T., Arnold, B., Scarritt, M. E., Pineda Molina, C., LoPresti, S. T., Brown, B. N., Naranjo, J. D., et al. (2017) · Tissue Engineering Part A · doi:10.1089/ten.tea.2017.0102 · Cited by 116 · see citing works
Zhuang, R. Z., Lock, R., Liu, B., & Vunjak-Novakovic, G. (2022) · Nature Biomedical Engineering · doi:10.1038/s41551-022-00885-3 · Cited by 84 · see citing works
A framework for developing sex-specific engineered heart models
Lock, R., Al Asafen, H., Fleischer, S., Tamargo, M., Zhao, Y., Radisic, M., & Vunjak-Novakovic, G. (2021) · Nature Reviews Materials · doi:10.1038/s41578-021-00381-1 · Cited by 50 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Hecking, J., Cano-Jorge, M., Passier, R., & Rivera-Arbeláez, J. M. (2026) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2025.1719533
“…positioned between two flexible micropillars, are ideal for examining cardiac contractile performance based on pillar deflection upon beating (Ronan et al., 2023; Liu et al., 2023; Windt et al., 2023; Ribeiro et al., 2022; Mannhardt et al., 2016; Hansen et al., 2010; Turnbull et al., 2014).”
- Authors
- Ronan, G., Bahcecioglu, G., Aliyev, N., & Zorlutuna, P.
- Affiliations
- University of Notre Dame (US)
- Venue
- Progress in Biomedical Engineering
- Publisher
- IOP Publishing
- Published
- 2023-12-08
- Volume
- 6
- Issue
- 1
- Pages
- 012002
- ISSN
- 2516-1091 (ISSN-L)
- OpenAlex
- W4388851258
- Cited by
- 4
- References
- 18
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 1
- FWCI
- 0.32
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Progress in Biomedical Engineering (publishedVersion, cc-by)
- Funders
- the National Institute of Health (NIH), National Heart, Lung, and Blood Institute (R01HL141909)
- National Science Foundation (1651385)
- 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 › Cell Biology › Cellular Mechanics and Interactions
- Keywords
- cardiac tissue engineering, bioprinting, extracellular matrix, heart development, cardiovascular disease, cardiac disease models, biomaterials, growth factors, machine learning, exosomes, microRNA, cardiac regeneration
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
