Date of Award
MS in Biomedical Engineering
Biomedical and General Engineering
Kristen O'Halloran Cardinal, Ph.D.
Coronary heart disease is the leading cause of death in the United States and occurs when plaque occludes coronary arteries. Coronary stents, which may be used to treat coronary occlusions, are small metal tubes that are implanted in coronary arteries to restore blood flow. After stent implantation, endothelial cells grow over the stent so that blood contacts the endothelial cells instead of the stent surface; this event is known as re-endothelialization. Re-endothelialization prevents blood from clotting on the stent surface and is a good predictor of stent success. Blood vessel mimics (BVMs) are in vitro tissue engineered models of human blood vessels that may be used to preclinically test coronary stents for re-endothelialization. BVMs have been developed in straight geometries, but the FDA has recommended that coronary devices be preclinically tested in complex-shaped simulated vessels when the complex geometries of coronary arteries may negatively affect device performance. Coronary geometries may negatively affect the tissue response to coronary stents, therefore BVMs should be developed in complex geometries.
The goal of this thesis research was to fully develop complex-shaped scaffolds and bioreactors, to develop complex-shaped BVMs with cells located throughout all regions of the BVMs, and to develop a complex-shaped BVM with a confluent region of cells. First, bioreactors that can house complex-shaped scaffolds were designed, constructed, and validated. Complex-shaped BVMs were then developed by depositing cells throughout the entire inner surface of complex-shaped scaffolds, and the average and median cell densities throughout all regions of the BVMs were shown to be approximately the same order of magnitude as endothelial cell densities in native blood vessels. A stent was then successfully deployed in a complex-shaped BVM. The complex-shaped BVM straightened out to conform to the stent, which also occurs in native blood vessels. Finally, a confluent region of cells was developed on a complex-shaped scaffold. Complex-shaped BVMs could eventually be used to preclinically test coronary stents, coronary drug-delivery systems, coronary imaging modalities, and other intravascular technologies.