Date of Graduation

5-2023

Document Type

Dissertation

Degree Name

Doctor of Philosophy in Engineering (PhD)

Degree Level

Graduate

Department

Chemical Engineering

Advisor/Mentor

Jorge Almodovar

Committee Member

Shannon Servoss

Second Committee Member

Raj Raghavendra Rao

Third Committee Member

Audie Thompson

Fourth Committee Member

Rebekah Margaret Samsonraj

Keywords

cell-based therapy, cell survival, cell environment

Abstract

Cell therapy is a technology that relies on replacing diseased or dysfunctional cells with healthy functioning ones. One of the cells used for such advanced therapies are stem cells, owing to their ability to differentiate into specific cells required for repairing damaged or defective tissues or cells. The majority of cell-based products are intended to transiently persist in the patient, secreting factors which then allow the patient’s body to heal; in these products, the cells are subsequently eliminated from the body. Furthermore, unique manufacturing platforms, in addition to novel commercialization strategies, will be required to create a successful, sustainable cell therapy industry. Currently in cell manufacturing companies, need to produce adherent cells, that bind to a solid surface such as tissue culture- treated plastic. In some cases, the growth surface needs to be treated or coated with a matrix (such as natural proteins) to facilitate cell adhesion. Cells can be grown on large flat surfaces or on spherical microcarriers for suspension?based culture in bioreactors. However, those proteins leading to batch-to-batch variability and concerns regarding contamination and affects the cell therapeutic potency. This thesis aims to develop techniques based on the merger of novel materials approaches to manipulate cell microenvironments in culture. For controlling cell-cell interaction and cell-soluble factor interactions, layer-by-layer deposition of ionic biopolymers were developed (Heparin as a negative charge polymer, collagen and Poly-L-Lysin are used as positive charge polymers). In addition, techniques were developed to control the viability of cells under hypoxic conditions within collagen hydrogels by controlling the three-dimensional properties of hydrogels and oxygen delivery (Perfluorocarbon-based oxygen carriers). In addition, to control cell-soluble factor interactions, Metal-Organic-Frameworks (MOFs) nanocarriers application was discussed as a carrier for delivering interferon-gamma (IFN-γ) to cells.

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