Cardiac-on-a-chip with microvascular plexus for drug testing and disease modeling

The advances in human stem cell technology and biofabrication techniques have generated a synergetic influence to accelerate research in the field of heart-on-a-chip. Functional cardiac tissues with microvascular plexus remain a challenge due to the highly condensed and organized tissue architecture and the complex multi-cell interactions. in the heart, fibroblasts, endothelial cells, and circulating and resident macrophages (Mac) play an important role in matrix deposition, vascularization, and paracrine signaling. Cardiac resident macrophages, which originate from the yolk sac, facilitate cardiac repair post-MI, and improve electrical conduction, angiogenesis, and CM, proliferation. Thus, the incorporation of Macs into engineered cardiac tissue is critical to achieving an adult-like, functional tissue.

Here, we incorporated four stem-cell-derived cells in two organ-on-chip devices: 1) the Biowire, to evaluate the cardiac function of the vascularized cardiac tissues with and without macrophages. Allowing assessment of contractile dynamics, electrical excitability and Ca2+ transient dynamics. 2) the iflow plate, to evaluate vascular function. Our results show a higher force of contraction and MCR along with enhanced vessel formation when Macs were incorporated into the tissues, demonstrating the importance of adding them into heart-on-a-chip platforms that can serve as a versatile tool for the research community for disease modeling and drug testing.