All ETDs from UAB

Advisory Committee Chair

Joel L Berry

Advisory Committee Members

Andra R Frost

Andrew Penman

Joanne Murphy-Ullrich

Timothy Wick

Document Type

Dissertation

Date of Award

2016

Degree Name by School

Doctor of Philosophy (PhD) School of Engineering

Abstract

Vascularized in vitro models of breast cancer represent an important advance in preclinical drug testing and development. 3D in vitro tissue models are more physiologically-relevant than 2D cell culture models due to the combination of human cells and extracellular matrix (ECM) in a spatial 3D microarchitecture. Embedding a vasculature within a 3D tissue volume further increases its physiological relevance and enables paracrine cross-talk with other cell types, neovascularization and angiogenesis, size-selective permeability between blood flow and extravascular ECM, delivery of therapeutics and metabolized products to solid tumors, delivery of circulating tumor cells to metastatic sites, and production of growth-promoting and growth-inhibiting substances. In this study, a perfusion-flow bioreactor housed the 3D ECM, composed of col I and BM, and allowed perfusion flow through embedded through-channels. When breast cancer cells were embedded within the ECM, perfusion flow through channels was shown to maintain cell viability compared to no flow and solid ECM. The mass transport of a macromolecule through the system was quantified to mimic drug delivery. Attachment, adhesion, and capillary-like tube formation of human mammary microvascular endothelial cells (HMMEC) was quantified to inform the seeding parameters of HMMEC into the through-channels. When HMMEC were seeded into through-channels, a HMMEC layer lined the through-channel walls forming engineered blood vessels. In the future, the vasculature and breast cancer models will be combined for drug development and testing. The engineered blood vessels will have applications in drug transport across the endothelium, cross-talk between EC and solid tumor cells, effects of fluid dynamics on cell phenotype, and regulation of angiogenesis.

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Engineering Commons

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