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What if the earliest signs of vascular disease could be observed as they unfold—inside lab-grown human blood vessels that mimic real-life conditions? This PhD research brings that possibility closer to reality through the creation of vascular avatars—living, human-based blood vessel models that simulate how the body functions.

Cardiovascular and kidney diseases are among the world’s leading causes of death. Yet, many traditional lab models fail to capture the complexity of human biology. To bridge this gap, advanced three-dimensional “vessel-on-a-chip” systems were developed. These miniaturized vessels, constructed from human cells and exposed to realistic blood flow and inflammation, recreate the early stages of disease with high precision. These platforms allow real-time observation of how damage begins in atherosclerosis and aneurysms—showing immune cell infiltration, plaque formation, and vessel wall weakening. Genetic conditions such as SMAD3 deficiency were also modeled to reveal how specific mutations contribute to vascular disorders.

The research further explores how mechanical forces—like matrix stiffness and rhythmic stretch—influence vascular smooth muscle cells derived from stem cells. The findings show how physical cues guide these cells toward a healthier, more contractile state, which is crucial for developing functional tissue-engineered vessels.

The thesis also investigates how tiny genetic changes—known as single nucleotide polymorphisms (SNPs)—linked to chronic kidney disease affect gene regulation. These insights lay the foundation for personalized kidney disease models.

Altogether, this body of work offers powerful tools and mechanistic insights into human disease. As the FDA recently signaled a move away from animal testing in favor of human-relevant methods, this research positions itself at the forefront of a more ethical, accurate, and personalized era in regenerative medicine.