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.
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Doctor of Philosophy (Ph.D.)
College of Engineering and Computer Science
Materials Science and Engineering
Materials Science & Engineering
Length of Campus-only Access
Doctoral Dissertation (Open Access)
Wang, Zi, "Processing of 3D Porous Biomaterial Scaffolds to Enhance The In Vitro Breast Cancer Tumor Microenvironment" (2021). Electronic Theses and Dissertations, 2020-. 1351.