Patient-Specific 3D Bioprinted Models of Developing Human Heart

• Authors: Alexander D Cetnar, Georgia Institute of Technology; Martin L Tomov, Georgia Institute of Technology; Liqun Ning, Georgia Institute of Technology; Bowen Jing, Georgia Institute of Technology; Andrea S Theus, Georgia Institute of Technology; Akassh Kumar, Georgia Institute of Technology; Amanda N Wijntjes, Georgia Institute of Technology; Sai Raviteja Bhamidipati, Texas A&M University; Katherine P Do, Emory University; Athanasios Mantalaris, Georgia Institute of Technology; John Oshinski, Emory University; Reza Avazmohammadi, Texas A&M University; Brooks D Lindsey, Emory University; Holly Bauser-Heaton, Emory University; Vahid Serpooshan, Emory University
• Journal Title: ADVANCED HEALTHCARE MATERIALS
• Volume: Volume 10, Number 15
• Publisher: WILEY | 2020-12-04, Pages e2001169-e2001169
• Type of Work: Article | Post-print: After Peer Review
• Publisher DOI: http://doi.org/10.1002/adhm.202001169
• Subjects: Engineering, Biomedical
• Keywords: Science & Technology; Technology; Engineering, Biomedical; Nanoscience & Nanotechnology; Materials Science, Biomaterials; Engineering; Science & Technology - Other Topics; Materials Science; 3D bioprinting; cardiovascular modeling; developing human heart; embryonic heart; fetal left ventricle; linear heart tubes; IPSC-DERIVED CARDIOMYOCYTES; PLURIPOTENT STEM-CELLS; CARDIAC DEVELOPMENT; HYDRAULIC PERMEABILITY; BLOOD-FLOW; DISEASE; DIFFERENTIATION; REGENERATION; MECHANISMS; SCAFFOLDS

Abstract

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.