Vasculature and flow in microfluidic systems

Kramer, B.

Drug development critically depends on preclinical models that mimic human physiology, yet traditional two-dimensional cultures and animal models often lack predictive power. This thesis explores the integration of vasculature and flow in microfluidic Organ-on-a-Chip systems to create more physiologically relevant in vitro models. First, a pancreatic ductal adenocarcinoma model incorporating interstitial flow was developed, demonstrating that fluid dynamics contribute to chemoresistance by inducing multidrug resistance proteins. Second, a Vascular-on-a-Chip model was established to study monocyte adhesion under flow, highlighting its utility in systems toxicology. Third, a high-throughput angiogenesis platform was created to investigate defective vascular responses in systemic sclerosis, showing the impact of patient sera and potential for drug screening. Finally, a robust imaging and quantification pipeline for three-dimensional vascular beds was introduced, enabling scalable...Show moreDrug development critically depends on preclinical models that mimic human physiology, yet traditional two-dimensional cultures and animal models often lack predictive power. This thesis explores the integration of vasculature and flow in microfluidic Organ-on-a-Chip systems to create more physiologically relevant in vitro models. First, a pancreatic ductal adenocarcinoma model incorporating interstitial flow was developed, demonstrating that fluid dynamics contribute to chemoresistance by inducing multidrug resistance proteins. Second, a Vascular-on-a-Chip model was established to study monocyte adhesion under flow, highlighting its utility in systems toxicology. Third, a high-throughput angiogenesis platform was created to investigate defective vascular responses in systemic sclerosis, showing the impact of patient sera and potential for drug screening. Finally, a robust imaging and quantification pipeline for three-dimensional vascular beds was introduced, enabling scalable assessment of angiogenesis. Together, these studies support the central hypothesis that incorporating vasculature and flow enhances physiological relevance, thereby improving disease modeling, toxicological assessment, and drug discovery.
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Vasculature and flow in microfluidic systems

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