The second generation of the CCCM system for in-vitro cardiac tissue engineering.

Abstract

Cardiovascular disease is the leading cause of death worldwide. When a myocardial infarction occurs, scar tissue compensates the damaged myocardial tissue. This scar tissue increases the stiffness of the heart tissue, reduces the heart’s function, and finally leads to the heart failure (HF) disease. To have the tissue engraftment, in-vitro cardiac tissue should have the same properties as the native mature cardiac tissue. However, current in-vitro cell culture technologies fail to accurately recreate the in-vivo like mechanically physiological environment for in-vitro cardiac tissue culture, and therefore, fail to regenerate the in-vivo like mature cardiac tissue. Hence, a microfluidic cardiac cell culture model (CCCM) system was developed to better recreate the cellular environment and advance cardiac regeneration. CCCM system replicates the hemodynamic loading and unloading conditions occurring inside the left ventricle of a heart. With this system, different pressures of human heart conditions may be replicated for a variety of clinical and physiologic conditions. For proof-of-concept, embryonic chick cardiac cells with normal heart condition were applied. Compared to the tissue cultured in a static condition, tissues stimulated in the CCCM system achieved an in-vivo like cardiac matured phenotype, had higher proliferating rate, showed more maturity, and expressed more contractile proteins. These results demonstrated that the CCCM system can be used to study the behavior of cardiomyocytes in different mechanical heart conditions and to create mature cardiac tissue which will benefit cardiac tissue transplant for HF