Electrical Stimulation Promotes the Vascularization and Functionalization of an Engineered Biomimetic Human Cardiac Tissue.

Abstract

The formation of multiscale vascular networks is essential for the in vitro construction of large-scale biomimetic cardiac tissues/organs. Although a variety of bioprinting processes have been developed to achieve the construction of mesoscale and large-scale blood vessels, the formation of microvascular networks still mainly depends on the self-assembly behavior of endothelial cells (ECs), which is inefficient and demanding without appropriate stimulus. To address this problem, the elongation and connection of endothelial cells in engineered cardiac tissue (ECT) are sought to promote by electrical stimulation (ES) to achieve vascularization. As proof of the concept, bio-inks are composed of GelMA/fibrin hydrogel, human pluripotent stem cells induced cardiomyocytes (iPSC-CM), and human umbilical vein endothelial cells (HUVEC) are used for the bioprinting of ECTs. It is demonstrated that electrical stimulation significantly promotes the elongation, migration, and interconnection of HUVECs in ECT and increases the expression of related genes. Moreover, ES also enhances the secretion of signal factors interacting between CMs and HUVECs. It seems that the HUVECs further strengthen the contractility of cardiac tissue. Taken together, electrical stimulation promotes vascularization and CMs functionalization in ECT, which has important application potential in the fabrication of vascularized ECT and its clinical transplantation.