Cardiovascular human organ-on-a-chip platform for disease modeling, drug development, and personalized therapy

Abstract

Cardiovascular organ-on-a-chip (OoC) devices are composed of engineered or native functional tissues that are cultured under controlled microenvironments inside microchips. These systems employ microfabrication and tissue engineering techniques to recapitulate human physiology. This review focuses on human OoC systems to model cardiovascular diseases, to perform drug screening, and to advance personalized medicine. We also address the challenges in the generation of organ chips that can revolutionize the large-scale application of these systems for drug development and personalized therapy.

Keywords: biomaterials; cardiovascular; organ-on-a-chip; organoid; stem cell.

FIGURE 1

Human iPSCs can be derived from patient somatic cells procured through a minimally invasive tissue biopsy and then reprogrammed using pluripotency factors. Human iPSCs can be used for disease modeling, pharmacokinetic and pharmacodynamic screening, and preclinical trials. Adapted with permission from Reference .

FIGURE 2

Vascular cell-on-a-chip system. (A) Fluorescence images of the monoculture model of the smooth muscle cells (SMCs) (red) and human umbilical vein endothelial cells (HUVECs) (green) in different microchannels. (B) Schemes illustrating the process of a layered co-culture model of the SMCs and HUVECs (left). Confocal image (right) of the co-culture model of the SMCs (blue) and HUVECs (green) with the vertical (red) and horizontal (yellow) cross-sections of the microchannel. The white dashed lines indicate the microchannel area. Reproduced with permission from Reference .

FIGURE 3

Vascularization strategies. (A) A single channel mimicking a vessel can be created by placing a hydrogel around a sacrificial conduit (e.g., needle etching), followed by coating the microconduit with endothelial cells (ECs). A cross-section of the vessel is shown at the far right of panel A. (B) Hollow EC-coated conduits can also be made using a microporous membrane to separate (i) matrix-filled chambers in a single-layer design or (ii) two adjacent fluid-filled chambers in a double-layer device. (C) Alternatively, ECs (red) and stromal cells (blue) can be mixed with a hydrogel and seeded in a device created using soft lithography under controlled interstitial flow (black arrows) and growth conditions to allow a vascular network to self-assemble. Vascular structures appear within 2–3 days, which then connect to form an interconnected, branched, and perfused microvasculature. A cross-section of the vessel is shown on the far right of panel C. Reproduced with permission from Reference .