All ETDs from UAB

Advisory Committee Chair

Joel L Berry

Advisory Committee Members

Andra Frost

Jillian Richter

Document Type

Thesis

Date of Award

2018

Degree Name by School

Master of Biomedical Engineering (MBE) School of Engineering

Abstract

Drug discovery and testing commonly employs two dimensional (2D) human cell line monolayers for lead compound identification before becoming a candidate therapy to be studied in animal models. Culturing cells in 2D produces a homogenous disbursement of nutrients and anticancer-therapeutics resulting in a response specific to 2D that does not necessarily translate to a three dimensional (3D) response. This method unfortunately distorts the in vivo human drug response. The lack of physiologic dimensionality in 2D cell monolayers distort cellular responses relative to 3D systems that can be attributed to minimal drug approvals. Oncology drugs are the least successful with only 5.1% of drugs making it to approval. To address the limitations of drug testing in 2D culture, our group previously created a 3D perfusion bioreactor system that incorporates a realistic volume and components of the tumor microenvironment to mimic human breast tumors. This has lead to the generation of reproducible breast tumor surrogates that support multi-week growth and viability allowing for the observation of treatment response over time. We propose to introduce an endothelial cell (EC) layer to line the walls of perfused microchannels in the system to better model the complexity of human tumors. EC are the main conduit of drug delivery to any target tissue and necessary to increase the fidelity of our model. EC provide a selectively permeable barrier controlling the diffusion of nutrients, gases, and drug dissemination to its respective tissue as well as contributing to cross talk with its environment. The incorporation of EC will allow us to more accurately mimic the cancer microenvironment’s response to preclinical anti-cancer therapeutics. This project aims to establish an EC barrier in response to a cancerous microenvironment to better understand drug dissemination.

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