摘要：SummaryFunctional three-dimensional (3D) engineered cardiac tissue (ECT) models are essential for effective drug screening and biological studies. Application of physiological cues mimicking those typical of the native myocardium is known to promote the cardiac maturation and functionalityin vitro. Commercially available bioreactors can apply one physical force type at a time and often in a restricted loading range. To overcome these limitations, a millimetric-scale microscope-integrated bioreactor was developed to deliver multiple biophysical stimuli to ECTs. In this study, we showed that the single application of auxotonic loading (passive) generated a bizonal ECT with a unique cardiac maturation pattern. Throughout the statically cultured constructs and in the ECT region exposed to high passive loading, cardiomyocytes predominantly displayed a round morphology and poor contractility ability. The ECT region with a low passive mechanical stimulation instead showed both rat- and human-origin cardiac cell maturation and organization, as well as increased ECT functionality.Graphical abstractDisplay OmittedHighlights•Mid-throughput culture platform to engineer reproducible 3D cardiacin vitromodels•3D culture under multiphysical stimuli mimicking thein vivoheart environment•Passive loading leads to bizonal constructs with different cardiac maturation stagesBiological sciences; Bioengineering; Tissue engineering; Biotechnology; Cell biology
