Dissertations and Theses

Date of Award

2018

Document Type

Thesis

Department

Mechanical Engineering

First Advisor

Jing Fan

Keywords

3D in vitro model, cell migration, breast cancer cells, soft lithography, PEGDA-GelMA microgels, Confocal microscopy, interstitial flow, concentration gradient, chemotaxis, microfluidics

Abstract

In vitro tissue models play an important role in providing a platform that mimics the realistic tissue microenvironment for stimulating and characterizing the cellular behavior. In particular, the hydrogel-based 3D in vitro models allow the cells to grow and interact with their surroundings in all directions, thus better mimicking in vivo than their 2D counterparts. The objective of this thesis is to establish a 3D in vitro model that mimics the anatomical and functional complexity of the realistic cancer microenvironment for conveniently studying the transport coupling in porous tissue structures. We pack uniform-sized PEGDA-GelMA microgels in a microfluidic chip to form a 3D porous model. The uniform-sized microgels were fabricated by capillary-based microfluidics; the microfluidic chip was designed and fabricated by soft lithography for conveniently handling gel packing and cell injection as well as controlling the interstitial flow through a syringe pump. To demonstrate the effectiveness of our model, we further examine the migration of the MDA-MB-231 breast cancer cells in the porous in vitro model in the presence of a concentration gradient of fetal bovine serum (FBS) and interstitial flow, respectively. The preliminary results show that the MDA-MB-231 cells can successfully grow and migrate in our in vitro model. Our ultimate goal is to apply this model to quantitatively study the combined effects of the interstitial flow and biomolecular diffusion on cell migration, which sheds light on understanding the mechanisms of tumor metastasis and many other physiological processes, such as the cellular response to drugs, the growth of connective tissues in bone and muscle, and the epithelial-cell behavior and morphogenesis.

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