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INTEGRATING ADVANCED 3D CELL CULTURE TECHNIQUES WITH RAPID-PROTOTYPING MICROFLUIDICS FOR TRANSLATIONAL APPLICATIONS

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title
INTEGRATING ADVANCED 3D CELL CULTURE TECHNIQUES WITH RAPID-PROTOTYPING MICROFLUIDICS FOR TRANSLATIONAL APPLICATIONS
author
Rajan, Shiny Amala Priya
abstract
3D cell culture recapitulates the physiological microenvironment more fully than 2D models by providing relevant physical and spatial interactions. These factors are known to affect cellular behavior by influencing signaling and gene expression pathways and are thus crucial to accurately represent in vivo systems. Microfluidics can further provide robust control, delivery, and analytical capabilities that would enable parallel testing of such 3D culture constructs in a miniaturized context. We have combined adhesive film-based rapid prototyping with a photopolymerizable hydrogel to produce 3D cell cultures in situ in the chambers of an active microfluidic device. We initially tested the biocompatibility, robustness, and stability of the platform for cell culture applications by integrating a series of healthy, tissue-like constructs (organoids) that included as many as 20 human primary cell types in total for an extended period. Having established a system that could maintain even sensitive primary cells with high viability, we then explored its capacity to support long-term drug studies, ultimately demonstrating multi-organ drug interactions. Next, we developed a tumor-on-a-chip model by incorporating non-passaged or low-passaged cells derived from patient tumor biopsies into the device architecture for personalized medicine applications. Then, we established a novel, multi-step photopatterning approach to producing devices for assaying cell invasion in vitro, performing validation experiments with both anti-proliferative and anti-migratory drugs. Finally, we integrated our projects by probing patient-derived tumor cells with the invasion assay to realize a drug screening platform with added functionality over conventional technologies. Ultimately, this dissertation advances our ability to develop sophisticated 3D tissue and disease models, provides an improved strategy for parallel drug testing, and enables cellular dynamics to be studied in vitro with efficiency in a low-cost microfluidic platform.
subject
3D model
Cancer
Microfluidics
Migration
Organ-on-a-chip
Tumor-on-a-chip
contributor
Hall, Adam R (committee chair)
Votanopoulos, Konstantinos I (committee member)
Verbridge, Scott S (committee member)
Munson, Jennifer M (committee member)
date
2020-01-08T09:35:23Z (accessioned)
2021-01-07T09:30:18Z (available)
2019 (issued)
degree
Biomedical Engineering (discipline)
embargo
2021-01-07 (terms)
identifier
http://hdl.handle.net/10339/95950 (uri)
language
en (iso)
publisher
Wake Forest University
type
Dissertation

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