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Advisory Committee Chair

Joel Berry

Advisory Committee Members

Erik Schwiebert

Palaniappan Sethu

Document Type

Thesis

Date of Award

2020

Degree Name by School

Master of Science in Biomedical Engineering (MSBME) School of Engineering

Abstract

Oscillatory forces such as blood pressure pulse, interstitial fluid flow, and body movement are present throughout ovarian tumors. These forces have been shown to strongly regulate mechanotransduction signaling, leading to tumor progression, metastasis, and invasion. Mechanotransduction studies are rarely conducted in ovarian cancer. This study is the first of its kind to understand how oscillatory forces impact ovarian tumor progression and the efficacy of a cancer therapeutic under these unique conditions. Herein, a novel oscillating flow bioreactor was developed housing an ovarian cancer tumor model using OVCAR-8 and IHFOT-208 cell lines and compared to the same bioreactor under constant flow. Initially, three bioreactors subjected to oscillating flow and three subjected to constant flow were run for seven days and measured for growth and cell density. Following these initial studies, experiments were conducted that introduced the chemotherapy drug Paclitaxel into the flow to discern the differing chemoresistance resulting from the different application of forces. Bioluminescent imaging was performed on day 0 and 7 of the growth experiments and on days 0, 5 and 7 in the chemoresistance experiments, and ROI measurements from these images were recorded. The samples were stained using H&E at the end of the experiments and cell density calculations were done. Results from the growth experiments showed an upward trend in growth in the oscillating bioreactors and a significantly higher cell density, most likely resulting from the inclusion of fibroblasts that were not luciferase tagged and therefore would not be included in the signal emitted during BLI imaging. Both BLI imaging signal and cell density calculations were significantly higher in the bioreactors under oscillatory flow than in constant flow. One mechanism for this result could be increased exosome release by the bioreactors under oscillating forces. Future directions of this project include proteomic work that would elucidate the signaling pathways underlying these results. Another utility of this model lies in its use as a preclinical model for drug development to increase the success rates of cancer therapeutics. The opportunities for the use of this bioreactor do not end with ovarian cancer but expand to other cancer types and diseases.

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