A myocardial infarct border-zone-on-a-chip demonstrates distinct regulation of cardiac tissue function by an oxygen gradient

After a myocardial infarction, the boundary between the injured, hypoxic tissue and the adjacent viable, nor-moxic tissue, known as the border zone, is characterized by an oxygen gradient. Yet, the impact of an oxygen gradient on cardiac tissue function is poorly understood, largely due to limitations of existing experimental models. Here, we engineered a microphysiological system to controllably expose engineered cardiac tissue to an oxygen gradient that mimics the border zone and measured the effects of the gradient on electromechanical function and the transcriptome. The gradient delayed calcium release, reuptake, and propagation; decreased diastolic and peak systolic stress; and increased expression of inflammatory cascades that are hallmarks of myo-cardial infarction. These changes were distinct from those observed in tissues exposed to uniform normoxia or hypoxia, demonstrating distinct regulation of cardiac tissue phenotypes by an oxygen gradient. Our border -zone-on-a-chip model advances functional and mechanistic insight into oxygen-dependent cardiac tissue pathophysiology.

Automated summary

This study engineered a microphysiological system to simulate an oxygen gradient environment in the border zone of a myocardial infarction, and investigated the effects of the gradient on cardiac tissue function and gene expression. The results showed that the oxygen gradient delayed calcium release, reuptake, and propagation, decreased diastolic and peak systolic stress, and increased expression of inflammatory pathways. These findings reveal distinct regulation of cardiac tissue phenotypes by an oxygen gradient.