Cardiac tissue modeling using flow microsystems and nanofiber mats: Evaluating hypoxia-induced cellular and molecular changes

Abstract

Myocardial cell regeneration research necessitates models that accurately represent heart tissues, especially in disease states. Our study unveils a unique Lab-on-a-chip system that combines polyurethane nanofiber mats, produced through solution-blown spinning, to simulate hypoxic conditions – a key factor in many heart diseases. This innovative microsystem's design includes specialized channels where hypoxia is achieved by flowing nitrogen over the culture chambers. We utilized two cell lines, human cardiomyocytes and rat cardiomyoblasts (H9c2), to assess the effects of this hypoxic environment on cell viability, morphology, and ATP levels. After 5 and 7 h of hypoxia exposure, H9c2 cells showed marked decreases in ATP levels. Additionally, there were pronounced reductions in the expression of cardiac function-related proteins such as MAP4K, TNNT2, SERCA, and SCN5A. This cutting-edge model allows for the simultaneous culture of myocardial cells in both hypoxic and normoxic conditions, positioning it as a pivotal tool for advances in regenerative medicine and cardiac tissue research. The observed impact of hypoxia on vital cardiac proteins expression in this system provides a deeper understanding of the mechanisms behind critical heart conditions, including myocardial infarction and heart failure.