Dissertation

Development of a healthy and diseased artery-on-a-chip

Cardiovascular diseases are a leading cause of death worldwide, and better models are urgently needed for disease progression studies and drug development.

Author: H.A. Ehlers
Date: 02 April 2025
Links: Thesis in Leiden Repository

A healthy artery is composed of several layers, two of which were used in the development of the model in this thesis. The innermost layer of cells facing the flowing blood is a monolayer of endothelial cells, also known as the endothelium. The second cell layer in the arteries is made of smooth muscle cells (SMCs) and surrounds the endothelial cell monolayer. The endothelium and smooth muscle cell layer are responsible for the vascular tone regulated by nitric oxide (NO) released from endothelial cells, causing the SMCs to dilate. The overall aim of the research described in this thesis is to develop and characterize models and assays for vascular inflammation and endothelial dysfunction using the OrganoPlate. Various assays or sensors, included a NO sensor, were incorporated into the models to detect small changes in endothelial dysfunction. Additionally, unidirectional versus bidirectional flow drastically affects the stability of the microfluidic vessels. Overall, these models show increased complexity compared to standard two-dimensional culture, increased by the benefit of coculture of various cell types.