The development of vascularized heart-on-chip models

The cardiovascular system, consisting of the heart and blood vessels, transports oxygen- and nutrient-rich blood throughout the body. A properly functioning cardiovascular system is essential for health, while cardiovascular diseases remain a leading cause of morbidity and mortality worldwide. The development of new drugs is costly and time-consuming, partly because many candidate drugs fail during clinical trials. Although these drugs are extensively tested in animal models beforehand, physiological differences between animals and humans can result in unexpected side effects. In vitro models using human cells provide an alternative, but they are often too simplistic to replicate the complexity of a whole organ. Organ-on-chip models increase this complexity by recreating key organ functions on a small scale. Further advancement of these models could improve the prediction of drug efficacy and safety, ultimately reducing the cost and time required for drug development.

In this thesis we aimed to increase the complexity of heart-on-chip systems through the addition of functional vasculature to the models. Vasculature was integrated by encapsulating pre-formed cardiac tissues with a hydrogel loaded with endothelial cells which formed a perfusable hydrogel, or by the creation of an additional vascular compartment using two photon polymerization printing. The creation of vascularized heart-on-chip systems is a major step forward in increasing the complexity of heart-on-chip models and will increase the predictive value of heart-on-chip models for disease modelling and drug testing.