Advisory Committee Chair
Advisory Committee Members
Mary Kathryn Sewell-Loftin
Date of Award
Degree Name by School
Doctor of Philosophy (PhD) School of Engineering
The current pathway for drug discovery is associated with costs of $2.55 billion and between 10-15 years of development for a single drug to reach the market. The challenges in predicting drug toxicities and efficacies are attributed to inherent species differences in drug-metabolizing enzyme activities and cell-type-specific sensitivities to toxicants. Organs-on-a-chip are an emerging technology in disease modeling and screening therapeutics to address discrepancies between animal models and human clinical trials. They utilize tissue engineering, fluid mechanics, and biomaterials to replicate in vivo architectures and functions of complex organs and tissues. Herein, the effect of pressure and stretch on bioengineered cardiac tissue and a spectrum fluidic shear stress on the renal proximal tubule epithelium are evaluated to elucidate how these stimuli play an important role in maintaining cellular phenotype and homeostasis. Additionally, human renal proximal tubule cells were cultured under physiological shear and pressure with known nephrotoxic or non-nephrotoxic compounds. Lastly, a more complex and novel bioengineered platform was developed of a 3D PT tubule and associated vascular networks. The organ-on-a-chips developed in this study will provide a technology that has broad applications in basic and translational research to model disease states, study interactions with other tissue chips, and accurately predict drug toxicity.
Donoghue, Leslie, "Renal Proximal Tubule Tissue Chips for Disease Modeling and Drug Toxicity Testing" (2023). All ETDs from UAB. 41.