Nanoscience and Microsystems ETDs

Publication Date

Summer 7-12-2018

Abstract

Drugs tested on animal models do not always produce the same results in humans; a reliable in vitro lung model can bridge the divide between the two. Because the alveolus is a target for several drugs, an alveolar model can be a platform for both designing drugs and studying lung diseases. A model should allow for gas exchange, growth of primary alveolar epithelial cells, extracellular matrix production, and have similar mechanical properties to alveoli, creating an environment conducive to normal metabolic activity and cellular responses. Existing artificial alveolar models that use polymeric membranes to sustain lung cells are limited by the necessary strain profile and the ability to maintain primary human alveolar cells. We are engineering an alveolus-on-a-chip device that simulates complex functional human alveoli, including the thin microporous alveolar barrier and the three-dimensional cyclic stretch induced by breathing movements. The design of this platform is optimized for robust fabrication, ease in cell culture manipulation, fluidic management and stretch activity. Furthermore, we are investigating two main types of primary alveolar cells culture in the alveoli which truly mimic the alveolar population. Our results suggest a use of this artificial alveolus in the development of an effective platform for rapid drug screening and pulmonary disease research.

Keywords

Alveolus-on-a-chip (AOC), Polyurethane (PU) membrane, Femtosecond (FS) laser, 5 µm pores, Primary Alveolar Cells, Air-liquid interface, Mechanical stretch, Continuous perfusion

Sponsors

Defense Threat Reduction Agency (DTRA) interagency agreement CBMXCEL-XL1-2-0001, 100271A5196

Document Type

Dissertation

Language

English

Degree Name

Nanoscience and Microsystems

Level of Degree

Doctoral

Department Name

Nanoscience and Microsystems

First Committee Member (Chair)

Steven W. Graves

Second Committee Member

Rashi S. Iyer

Third Committee Member

Jennifer F. Harris

Fourth Committee Member

Andrew P. Shreve

Fifth Committee Member

David G. Whitten

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