Rapid 3D bioprinting of in vitro cardiac tissue models using human embryonic stem cell-derived cardiomyocytes.

Abstract

There is a great need for physiologically relevant 3D human cardiac scaffolds for both short-term, the development of drug testing platforms to screen new drugs across different genetic backgrounds, and longer term, the replacement of damaged or non-functional cardiac tissue after injury or infarction. In this study, we have designed and printed a variety of scaffolds for in vitro diagnostics using light based Micro-Continuous Optical Printing (μCOP). Human embryonic stem cell-derived cardiomyocyte (hESC-CMs) were directly printed into gelatin hydrogel on glass to determine their viability and ability to align. The incorporation of Green Fluorescent Protein/Calmodulin/M13 Peptide (GCaMP3)-hESC-CMs allowed the ability to continuously monitor calcium transients over time. Normalized fluorescence of GCaMP3-hESCCMs increased by 18 ± 6% and 40 ± 5% when treated with 500 nM and 1 μM of isoproterenol, respectively. Finally, GCaMP3-hESC-CMs were printed across a customizable 3D printed cantilever-based force system. Along with force tracking by visualizing the displacement of the cantilever, calcium transients could be observed in a non-destructive manner, allowing the samples to be examined over several days. Our μCOP-printed cardiac models presented here can be used as a powerful tool for drug screening and to analyze cardiac tissue maturation.