Item Details

title

Development of Combined 3-Dimensional Tissue Culture and Microfluidics Systems for Use in the Study of Disease States and Their Treatments

author

Hauser, Nathaniel Loren

abstract

In vitro modeling is an important step in the study of disease within the body and the mechanisms and effects of treatments. However, a majority of in vitro models utilize static 2D cell culture which has been consistently shown to have poor translation into in vivo and clinical models due to the unnatural format of 2D culture and its detrimental effect on cell morphology and behavior. 3D cell culture addresses this deficiency somewhat through the simulation of ECM and a more natural arrangement of cells within created structures, but still falls short in static cultures due to the lack of mechanical forces that have been found to be important in a number of cell fate processes. In this thesis we will address this deficiency by combining 3D cell culture with microfluidic systems in order to add a high degree of control over the physical forces present within out simulated microenvironments. Here we will design and test a number of in vitro combined microfluidic and 3D culture systems in order to study a range of disease states and their possible treatments. Furthermore, this thesis focuses on the use of adhesive film based microfluidic systems (AFBs) which are notable in their ability to be quickly prototyped and adapted as well as being easily capable of mass production for use in translational medicine.Specifically we will optimize a cancer migration model chip for use in precision medicine study and the treatment of glioblastoma multiforme (GBM). Then we will utilize a novel combined tumor and antigen presenting cell organoid system contained within a microfluidic chip in order to generate tumor reactive T-cells with effectiveness on par with currently available immune therapies using patient derived samples. Finally, we will evaluate a lung on a chip model for use in radio-protectant testing. This model was found to have noticeable difference compared to traditional 2D models in how radiation induced apoptosis and DNA DSBs occurred and demonstrated significant reduction in cellular damage with the introduction of a radioprotectant.

subject

Cancer

Immune System

Lung

Microfluidics

Tissue Engineering

contributor

Hall, Adam R (committee chair)

Murphy, Sean V (committee member)

Weis, Jared A (committee member)

date

2021-09-01T08:35:39Z (accessioned)

2023-08-31T08:30:06Z (available)

2021 (issued)

degree

Biomedical Engineering (discipline)

embargo

2023-08-31 (terms)

identifier

http://hdl.handle.net/10339/99075 (uri)

language

en (iso)

publisher

Wake Forest University

type

Thesis