Date of Award

2020

Document Type

Open Access Master's Thesis

Degree Name

Master of Science in Biomedical Engineering (MS)

Administrative Home Department

Department of Biomedical Engineering

Advisor 1

Smitha Rao

Committee Member 1

Jeremy Goldman

Committee Member 2

Marina Tanasova

Abstract

Tumorigenesis is a complex process involving numerous cellular signaling cascades and environmental factors. Here, we report the fabrication of 3D scaffolds with different morphologies obtained by to study cancer cell proliferation and migration. Using an FDA approved, biocompatible and biodegradable polymer Polycaprolactone (PCL), we electrospun nanofiber scaffolds having mesh, aligned, and honeycomb morphologies. The role of the morphology and cellular preferences to nutrition in cell adhesion and proliferation was assessed using scaffolds obtained by electrospinning PCL with fluorescent fructose-like molecular probes. Cell viability, cell morphology, localized cellular growth as related to scaffold morphology and availability of the fructose-like molecular probes were investigated. The changes in biophysical properties of tumor microenvironment with change in morphology of the scaffolds were observed. In vitro tests for proliferation, alignment and migration of human dermal fibroblasts (HDFa), normal breast epithelial cells (184B5), adenocarcinoma (MCF-7), pre-malignant (MCF10AneoT) and triple-negative (MDA-MB-231 on the scaffolds on days 1, 2, and 3 were carried out. The morphology of the scaffolds was characterized using FE-SEM while surface characterization was done using FTIR. Mechanical properties of the scaffolds were investigated using a Dynamic Mechanical Analyzer (DMA). Cell proliferation was assessed using CellTiter-Blue® Viability Assay; migration and cell-scaffold interactions were investigated using phalloidin for F-Actin. Our data indicates that while topographical features affected cell adhesion and proliferation, cell lines that responded to the fructose-like probes tended to be more invasive. Furthermore, the preference to a specific scaffold was greatly altered by the presence of the probes with MDA-MB-231 showing least preference after 72 hours and pre-malignant MCF10AneoT showing highest preference. However, there was no significant difference in the cell numbers between scaffolds with probes and those without for the pre-malignant cells while this difference was noticeable in the control cell lines. Hence, a relation between cell preferences, scaffold morphology and nutritional sources may be sought by further exploring this approach.

Available for download on Tuesday, April 20, 2021

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