Three-dimensional (3D) cell cultures have been widely used in biological research since two-dimensional (2D) cultures have many limitations including alteration of cell morphology, metabolic pathways and gene expression. Therefore, the application of 2D cell cultures in pharmaceutical companies for drug screening causes reproducibility issues in animal studies, which strongly influences the efficiency of drug development. The aim of my studies is to develop 3D cell culture models to better mimic the extracellular matrix (ECM) in tumor microenvironment, not only for deeper understanding of interaction between cells and ECM, but also for the application in drug screening. Three different compositions of chitosan-alginate (CA) scaffolds with different stiffness were produced to mimic prostate cancer (PCa) progression stages. The results showed that PCa cells demonstrated stiffness independent growth and protein expression. But surprisingly, it was found that CA scaffolds could identify PCa cell phenotypic characteristics. Further, a novel 3D porous chitosan-chondroitin sulfate (C-CS) scaffold, with three CS compositions, were developed to mimic the PCa progression, since the clinical research has suggested that the CS is found in normal prostate tissue, greater in PCa, and further in metastatic sites. The results showed that CS can promote PCa cell metastasis-related gene expression and anti-cancer drug resistance. Although CA and C-CS scaffold provided more insights on PCa, 3D cell culture is more complicated to use than 2D cultures, which limited its application in industry. Therefore, a novel biomaterial format, named Frozen Films, were developed to combine the advantages of 2D and 3D culture while reducing their drawbacks. Cell cultures tested on Frozen Films demonstrated that cells had 3D culture performance, but with much easier operation process. Overall, those studies demonstrated that CA scaffolds, C-CS scaffolds and Frozen Films could be promising in vitro platforms for cellular research, with potential applications for in vitro anti-cancer drug screening.
| Identifer | oai:union.ndltd.org:ucf.edu/oai:stars.library.ucf.edu:etd2020-1818 |
| Date | 01 January 2020 |
| Creators | Xu, Kailei |
| Publisher | STARS |
| Source Sets | University of Central Florida |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | Electronic Theses and Dissertations, 2020- |
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