FRESH™ 3D bioprinted cardiac tissue, a bioengineered platform for in vitro pharmacology

作者：Samuel Finkel, Shannon Sweet, Tyler Locke, Sydney Smith, Zhefan Wang, Christopher Sandini, John P. Imredy, Yufang He, Marc R. Durante, Armando Lagrutta, Adam W. Feinberg, Andrew Lee · 发表于：APL Bioengineering · 年份：2023 · DOI：10.1063/5.0163363 · 被引用次数：32 · 研究领域：3D Printing in Biomedical Research、Pluripotent Stem Cells Research、Tissue Engineering and Regenerative Medicine

There is critical need for a predictive model of human cardiac physiology in drug development to assess compound effects on human tissues. In vitro two-dimensional monolayer cultures of cardiomyocytes provide biochemical and cellular readouts, and in vivo animal models provide information on systemic cardiovascular response. However, there remains a significant gap in these models due to their incomplete recapitulation of adult human cardiovascular physiology. Recent efforts in developing in vitro models from engineered heart tissues have demonstrated potential for bridging this gap using human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) in three-dimensional tissue structure. Here, we advance this paradigm by implementing FRESH™ 3D bioprinting to build human cardiac tissues in a medium throughput, well-plate format with controlled tissue architecture, tailored cellular composition, and native-like physiological function, specifically in its drug response. We combined hiPSC-CMs, endothelial cells, and fibroblasts in a cellular bioink and FRESH™ 3D bioprinted this mixture in the format of a thin tissue strip stabilized on a tissue fixture. We show that cardiac tissues could be fabricated directly in a 24-well plate format were composed of dense and highly aligned hiPSC-CMs at >600 million cells/mL and, within 14 days, demonstrated reproducible calcium transients and a fast conduction velocity of ∼16 cm/s. Interrogation of these cardiac tissues with t...