Abstract

Tumors contain heterogeneous cell populations within the tumor microenvironment (TME). TME supports tumor progression and development via the function of multiple cell types and cell-extracellular matrix (ECM) interactions. 3D porous biomaterial scaffolds can be a type of in vitro tumor models to mimic TME ECM. Current tumor models lack structural complexity replicating tumor ECM, tunable mechanical properties, and have limited mass exchange between cells and their microenvironment. In this work, we firstly developed scaffolds with a hierarchical pore structure via the Freeze-FRESH(FF) fabrication technique that combines 3D printing and freeze-casting. Later, we studied the effect of varying processing parameters and different type I collagen presentations in chitosan-hyaluronic acid (C-HA) scaffolds on breast cancer (BCa) cell response. FF scaffolds exhibited greater resiliency and promoted MDA-MB-231 (231) cell growth and multicellular clusters formation. Varying C-HA compositions resulted in varied scaffold pore size and stiffness, and the different scaffold properties promoted multiple hybrid epithelial/mesenchymal (E/M) BCa phenotypes. However, C-HA scaffolds lack the native ECM protein components that provide ligands for cell adhesion, which limits cell function. Therefore, collagen was incorporated into C-HA scaffolds with different presentations to improve cell-material interactions. All scaffolds promoted hybrid E/M phenotypes for 231 and MCF-7 cells. Scaffolds with collagen embedded as hydrogel promoted a more aggressive phenotype with the greater mesenchymal extent and the greatest docetaxel resistance. In summary, the porous biomaterial scaffolds developed and processed in this work produced the enhanced in vitro BCa TME.

Notes

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Graduation Date

2021

Semester

Fall

Advisor

Crawford, Kaitlyn

Degree

Doctor of Philosophy (Ph.D.)

College

College of Engineering and Computer Science

Department

Materials Science and Engineering

Degree Program

Materials Science & Engineering

Identifier

CFE0009322; DP0026926

URL

https://purls.library.ucf.edu/go/DP0026926

Language

English

Release Date

June 2023

Length of Campus-only Access

1 year

Access Status

Doctoral Dissertation (Open Access)

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