Date of Award

Spring 2018

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Electrical & Computer Engineering

Committee Director

Patrick C. Sachs

Committee Director

Dean J. Krusienski

Committee Member

Christian W. Zemlin

Committee Member

Roy C. Ogle

Abstract

Understanding the microenvironmental factors that control cell function, differentiation, and stem cell renewal represent the forefront of developmental and cancer biology. To accurately recreate and model these dynamic interactions in vitro requires both precision-controlled deposition of multiple cell types and well-defined three-dimensional (3D) extracellular matrix (ECM). To achieve this goal, we hypothesized that accessible bioprinting technology would eliminate the experimental inconsistency and random cell-organoid formation associated with manual cell-matrix embedding techniques commonly used for 3D, in vitro cell cultures. The first objective of this study was to adapt a commercially-available, 3D printer into a 3D bioprinter. Goal-based computer simulations were used to identify, evaluate, and optimize the performance of a 3D bioprinting system. Implementing these findings yielded a bioprinting system with reduced needle clogging and single cell print resolution. The minimal disruption of cell function was confirmed by the retention of pluripotency marker TRA-1-81 in bioprinted human induced pluripotent stem cells (hiPSCs) 7-days post-printing. This system was then used to investigate cell behavior during the initial stages of organoid-structure formation by generating 3D bioprinted arrays of individual, mammary epithelial cell (MEC) organoid-structures. This quantifiable, 3D bioprinting approach, was able to direct the ‘self-assembly’ of large MEC structures through organoid ‘fusion’ events among individual, bioprinted organoids along the printing template. Bioprinting maintained experimental consistency among multiple 3D scaffolds and experimental conditions, and presents the capability to generate high-fidelity, 3D arrays with multiple cell types. Compared to manual matrix embedding, bioprinted, co-culture experiments, containing normal MECs and breast cancer cell lines, significantly increased the ability to generate chimeric (tumor/normal) MEC structures. Thus, bioprinting stands highly qualified to investigate the role of microenvironmental processes related to cell fate determination and tissue formation.

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DOI

10.25777/d1hj-6a76

ISBN

9780355884067

ORCID

0000-0003-2989-1292

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