Rapid 3D BioPrinting of a human iPSC-derived cardiac micro-tissue for high-throughput drug testing
Kathleen L. Miller, Yi Xiang, Claire Yu, Jacob Pustelnik, Jerry Wu, Xinyue Ma, Toshikatsu Matsui, Kenichi Imahashi, Shaochen Chen
Abstract
With cardiac disease a reigning problem in the world, the need for accurate and high-throughput drug testing is paramount. 3D cardiac tissues are promising models, as they can recapitulate the cell-cell, cell-matrix, and cell-tissue interactions that impact response to a drug. Using an in-house developed micro-continuous optical printing system, we created a cardiac micro-tissue in mere seconds with microscale alignment cues in a hydrogel scaffold that is small enough to fit in a 96-well plate. The 3D printed, asymmetric, cantilever-based tissue scaffold allows one to directly measure the deformation produced by the beating micro-tissue. After 7 days, the micro-tissue exhibited a high level of sarcomere organization and a significant increase in maturity marker expression. The cardiac micro-tissues were validated against two representative drugs, isoproterenol and verapamil at various doses, showing corresponding and measurable changes in beating frequency and displacement. Such rapidly bioprinted cardiac micro-tissues in a multi-well plate offer a promising solution for high-throughput screening in drug discovery.