All ETDs from UAB

Advisory Committee Chair

Joel L Berry

Advisory Committee Members

Andra R Frost

Andrew Penman

Joanne Murphy-Ullrich

Timothy M Wick

Document Type

Thesis

Date of Award

2013

Degree Name by School

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

Abstract

There is a need for more effective therapies to combat breast cancer. One reason for the inefficiency of therapeutics is that testing technologies currently employed in drug discovery and development are not reliable when transitioning drugs into human clinical trials. To supplement the currently used in vitro cell culture studies and in vivo animal studies, an in vitro three-dimensional breast tumor system has been suggested with integration of human cells, hydrogel biomaterials, 3D architecture, and endothelialized microchannels. Therefore, the objective of the thesis project, as an initial step in fabrication of the supplemental system for drug testing, is to fabricate and characterize a tissue volume with pre-fabricated EC-lined microchannels representing the vasculature of a breast tumor. It is hypothesized that an in vitro three-dimensional microphysiologic system can be constructed with extracellular matrix and flow-through microchannels that will support a confluent endothelial layer. Results have shown that fabricated three-dimensional microenvironments, composed of extracellular matrix components, had a matrix elasticity similar to that of normal mammary tissue. An iterative design process of bioreactor fabrication led to a bioreactor that could contain a three-dimensional scaffold with a mean wall shear stress in the range of 0-5 dyne/cm2 inside the microchannels. In addition, the bioreactor system and endothelialization protocol facilitated the localization and attachment of endothelial cells inside the prefabricated microchannels. Future work will include further characterization of endothelial cell morphology and function and assessment of barrier function and permeability of the engineered endothelium. Continuation of this proof-of-concept project will lead to the formation of a confluent endothelial cell monolayer, which may be used to perfuse the three-dimensional tissue-engineered scaffold, to act as a dissemination route for tumor cells, or to act as a route for therapeutics to the tumor site.

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