Organ-on-a-chip technology: a novel approach to investigate cardiovascular diseases

Abstract

The development of organs-on-chip (OoC) has revolutionized in vitro cell-culture experiments by allowing a better mimicry of human physiology and pathophysiology that has consequently led researchers to gain more meaningful insights into disease mechanisms. Several models of hearts-on-chips and vessels-on-chips have been demonstrated to recapitulate fundamental aspects of the human cardiovascular system in the recent past. These 2D and 3D systems include synchronized beating cardiomyocytes in hearts-on-chips and vessels-on-chips with layer-based structures and the inclusion of physiological and pathological shear stress conditions. The opportunities to discover novel targets and to perform drug testing with chip-based platforms have substantially enhanced, thanks to the utilization of patient-derived cells and precise control of their microenvironment. These organ models will provide an important asset for future approaches to personalized cardiovascular medicine and improved patient care. However, certain technical and biological challenges remain, making the global utilization of OoCs to tackle unanswered questions in cardiovascular science still rather challenging. This review article aims to introduce and summarize published work on hearts- and vessels-on chips but also to provide an outlook and perspective on how these advanced in vitro systems can be used to tailor disease models with patient-specific characteristics.

Keywords: Cardiovascular; Cell culture; Heart; Organs-on-chips; Personalized medicine.

Figure 1

Fabricating heart-on-chip and vessel-on-chip models using micromachining allows for integration of several advanced features.

Figure 2

Schematic drawing showing the six basic steps of PDMS moulding to form a microfluidic channel that can be used in organs-on-chip. 1—A master is prepared having the inverse topography of the final channel structures, 2—PDMS pre-polymer is poured onto the master and polymerised upon heat treatment, 3—The moulded channels are released from the master, 4—Holes for connecting tubing for media perfusion are prepared in the PDMS by punching, 5—The PDMS surface is activated for bonding via plasma treatment, 6—The microfluidic channels are sealed by bonding the PMDS slab onto a glass microscope slide which may include patterned electrodes.

Figure 3

Heart-on-chip devices can recapitulate cardiac functions in vitro and integrate sensing units to monitor the cells in culture, e.g. action potential. Examples of cardiovascular diseases can be found in these devices, such as ischaemia and cardiac fibrosis. Integrated electrodes and mechanical actuation allow to monitor and stimulate the cells in culture, better recapitulating the cardiac microenvironment.

Figure 4

Vessels-on-chips devices are useful tools to study pathological mechanisms occurring within the vessel wall in early and later stages of atherosclerosis. Preliminary research can be performed in easier fabricated straight PDMS channels, whereas for more extensive and complicated research questions, a more elaborate model can be used by producing a 3D lumen in a hydrogel.