Blood-perfused Vessels-on-Chip for disease modelling and precision medicine
Huub Weener is a PhD Student in the department Applied Stem Cell Technologies. (Co)Promotors are prof.dr. A.D. van der Meer and prof.dr. P.C.J.J. Passier from the faculty Science & Technology, University of Twente.
The endothelium—the inner lining of our blood vessels—is essential to vascular health, acting as both a protective barrier and a regulator of blood clotting and immune activity. When functioning properly, endothelial cells prevent unnecessary clot formation and inflammation. However, in diseases or under the influence of certain drugs, this protective layer can become compromised, triggering a cascade of harmful responses such as increased clotting, immune cell activation, and vessel leakage.
This thesis presents the development of a cutting-edge blood-perfused Vessel-on-Chip model—a miniature, dynamic replica of a blood vessel designed to mimic real-life vascular conditions. By using living human cells and perfusing them with fresh human blood, this system offers an unprecedented window into the real-time behavior of the endothelium under both healthy and diseased states.
One of the key applications of this model was the investigation of COVID-19-associated vascular complications. When exposed to blood plasma from hospitalized COVID-19 patients, the Vessel-on-Chip revealed distinct signs of endothelial dysfunction. These included increased platelet aggregation, inflammatory signaling, and a phenomenon called NETosis—a response where immune cells release DNA traps that can further damage the vasculature. These findings offer critical insight into how COVID-19 affects blood vessels and supports the use of this model for studying systemic inflammatory diseases.
The model was also used to examine the vascular side effects of CAR-T cell therapy, a powerful cancer treatment known to sometimes trigger dangerous inflammatory reactions. By simulating the cytokine-rich environment seen in patients undergoing this therapy, the Vessel-on-Chip showed that immune activation—especially from macrophages—can lead to vessel barrier breakdown, clot formation, and inflammation. Importantly, treatment with low molecular weight heparin significantly reduced these effects, demonstrating the model’s value in evaluating both drug side effects and potential interventions.
Beyond its biological insights, this research also addresses how such advanced models can become more widely accepted in applied settings beyond the academic field, like pharmaceutical, toxicological, and regulatory industry. It proposes key strategies to improve reliability, reduce dependency on animal-derived materials, and ensure that these models can be standardized and validated for broader use.
This work highlights the vast potential of blood-perfused Vessel-on-Chip platforms to transform how we study vascular disease, test new drugs, and tailor therapies to individual patients. By recreating complex human biology in the lab, these systems may one day bridge the gap between laboratory research and real-world clinical care.
