Conventional pre-clinical drug screening, reliant on 2D cell cultures and animal studies, faces challenges—the former lacks biological complexity, and the latter lacks predictability due to differences between animals and humans from genetic to functional levels. Organ-on-chip technologies have evolved to bridge the gap between preclinical and clinical trials, necessitating human cells for precise predictions of human responses. Considering the significance of the vascular system in various diseases, incorporating vascular units into organ-on-chip devices is critical. For effective drug discovery using vessels-on-chips, achieving high-throughput and consistency between samples is crucial. However, many vessels-on-chips are manually handled during preparation and data collection, reducing throughput and increasing sample-to-sample variations. The conventional closed microfluidic chip format further impedes accessibility, hindering automation. This thesis focuses on two high-throughput micro-vessel models replicating vascular functions under perfusion in a 384-well plate format. These open-top models allow automated preparation and examination, enhancing efficiency in compound screening. The first model features a self-assembled perfusable micro-vascular network on a 384-well plate, co-culturing endothelial cells (EC) with stromal cells in a hydrogel. Automated using a robotic system and a fluorescent plate reader, it supports organ-specific functions and enables nanoparticle transport to target tissues. Utilized for testing cancer therapeutic drugs, it demonstrates dose-related responses in vascular permeability and architectures. The second model is dedicated to crafting micro-vessels of consistent quality for biological testing and disease modeling. It employs a sacrificial material for pre-designed tubular shapes for EC seeding. The integration of automated processes and a straight channel design minimizes sample discrepancies. Furthermore, a tri-culture system enhances barrier integrity, enabling effective drug screening that distinguishes between vasculotoxic and non-vasculotoxic agents with notable sensitivity and specificity. Looking ahead, there is potential to further refine these models to encompass a broader range of vascular diseases, which could lead to novel insights and therapeutic targets. / Thesis / Doctor of Philosophy (PhD) / In clinical trials, a staggering 90% of drugs fail during testing in people. Traditional preclinical drug screening methods rely on culturing human cells on flat surfaces or using animal models, both fraught with limitations such as lacking structural complexity or having DNA differences from humans. Addressing this issue could notably reduce efforts and costs. This thesis is dedicated to advancing preclinical drug testing through micro-vessel models. It focuses on constructing 3D vessels using human cells, offering a more accurate representation of human physiology. Two models are discussed: one with self-assembled vessels featuring complex structures, and another emphasizing sacrificial materials to design simpler vascular shapes, ensuring consistency in testing. By leveraging these innovative models, researchers can subject various drugs to micro-vessels constructed in vitro, enabling them to predict their effects in humans. This approach has the potential to transform drug testing methodologies, moving towards the utilization of artificial human organ models.