TY - JOUR
T1 - Patient-Specific 3D Bioprinted Models of Developing Human Heart
AU - Cetnar, Alexander D.
AU - Tomov, Martin L.
AU - Ning, Liqun
AU - Jing, Bowen
AU - Theus, Andrea S.
AU - Kumar, Akaash
AU - Wijntjes, Amanda N.
AU - Bhamidipati, Sai Raviteja
AU - Do, Katherine Pham
AU - Mantalaris, Athanasios
AU - Oshinski, John N.
AU - Avazmohammadi, Reza
AU - Lindsey, Brooks D.
AU - Bauser-Heaton, Holly D.
AU - Serpooshan, Vahid
N1 - Funding Information:
A.D.C. and M.L.T. contributed equally to this work. The authors are grateful for the expert technical assistance and help provided by Sassan Hashemi and Timothy Slesnick. The authors would like to also acknowledge Dr. Alejandro Roldán-Alzate and his team at University of Wisconsin-Madison for providing the fetal human heart data, Dr. Bjarke Jensen at University of Amsterdam for providing the embryonic human heart data, and Alessandro Veneziani for his help in computational modeling. This research was funded by the NIH grant number R00HL127295 and Emory University School of Medicine (Pediatric Research Alliance Pilot Grant and the Dean's Imagine, Innovate and Impact (I3) Research Award). This research was also funded in part by the Department of Biomedical Engineering and the College of Engineering at Georgia Institute of Technology and by R01HL144714 and R00HL138288 from the National Institutes of Health.
Funding Information:
A.D.C. and M.L.T. contributed equally to this work. The authors are grateful for the expert technical assistance and help provided by Sassan Hashemi and Timothy Slesnick. The authors would like to also acknowledge Dr. Alejandro Roldán‐Alzate and his team at University of Wisconsin‐Madison for providing the fetal human heart data, Dr. Bjarke Jensen at University of Amsterdam for providing the embryonic human heart data, and Alessandro Veneziani for his help in computational modeling. This research was funded by the NIH grant number R00HL127295 and Emory University School of Medicine (Pediatric Research Alliance Pilot Grant and the Dean's Imagine, Innovate and Impact (I3) Research Award). This research was also funded in part by the Department of Biomedical Engineering and the College of Engineering at Georgia Institute of Technology and by R01HL144714 and R00HL138288 from the National Institutes of Health.
Publisher Copyright:
© 2020 Wiley-VCH GmbH
PY - 2021/8/4
Y1 - 2021/8/4
N2 - The heart is the first organ to develop in the human embryo through a series of complex chronological processes, many of which critically rely on the interplay between cells and the dynamic microenvironment. Tight spatiotemporal regulation of these interactions is key in heart development and diseases. Due to suboptimal experimental models, however, little is known about the role of microenvironmental cues in the heart development. This study investigates the use of 3D bioprinting and perfusion bioreactor technologies to create bioartificial constructs that can serve as high-fidelity models of the developing human heart. Bioprinted hydrogel-based, anatomically accurate models of the human embryonic heart tube (e-HT, day 22) and fetal left ventricle (f-LV, week 33) are perfused and analyzed both computationally and experimentally using ultrasound and magnetic resonance imaging. Results demonstrate comparable flow hemodynamic patterns within the 3D space. We demonstrate endothelial cell growth and function within the bioprinted e-HT and f-LV constructs, which varied significantly in varying cardiac geometries and flow. This study introduces the first generation of anatomically accurate, 3D functional models of developing human heart. This platform enables precise tuning of microenvironmental factors, such as flow and geometry, thus allowing the study of normal developmental processes and underlying diseases.
AB - The heart is the first organ to develop in the human embryo through a series of complex chronological processes, many of which critically rely on the interplay between cells and the dynamic microenvironment. Tight spatiotemporal regulation of these interactions is key in heart development and diseases. Due to suboptimal experimental models, however, little is known about the role of microenvironmental cues in the heart development. This study investigates the use of 3D bioprinting and perfusion bioreactor technologies to create bioartificial constructs that can serve as high-fidelity models of the developing human heart. Bioprinted hydrogel-based, anatomically accurate models of the human embryonic heart tube (e-HT, day 22) and fetal left ventricle (f-LV, week 33) are perfused and analyzed both computationally and experimentally using ultrasound and magnetic resonance imaging. Results demonstrate comparable flow hemodynamic patterns within the 3D space. We demonstrate endothelial cell growth and function within the bioprinted e-HT and f-LV constructs, which varied significantly in varying cardiac geometries and flow. This study introduces the first generation of anatomically accurate, 3D functional models of developing human heart. This platform enables precise tuning of microenvironmental factors, such as flow and geometry, thus allowing the study of normal developmental processes and underlying diseases.
KW - 3D bioprinting
KW - cardiovascular modeling
KW - developing human heart
KW - embryonic heart
KW - fetal left ventricle
KW - linear heart tubes
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U2 - 10.1002/adhm.202001169
DO - 10.1002/adhm.202001169
M3 - Article
C2 - 33274834
AN - SCOPUS:85097029296
SN - 2192-2640
VL - 10
JO - Advanced Healthcare Materials
JF - Advanced Healthcare Materials
IS - 15
M1 - 2001169
ER -