Date of Award

Summer 8-2022

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Electrical & Computer Engineering

Program/Concentration

Biomedical Engineering

Committee Director

Robert Bruno

Committee Director

Venkat Maruthamuthu

Committee Member

Patrick Sachs (Co-Chair)

Committee Member

Michel Audette

Abstract

The cellular microenvironment varies significantly across tissues, and it is constituted by both resident cells and the macromolecules they are exposed to. Cues that the cells receive from the microenvironment, as well as the signaling transmitted to it, affect their physiology and behavior. This notion is valid in the context of stem cells, which are susceptible to biochemical and biomechanical signaling exchanged with the microenvironment, and which plays a fundamental role in establishing fate determination and cell differentiation events. The definition of the molecular mechanisms that drive stem cell asymmetrical division, and how these are modulated by microenvironmental signaling, is challenging. Important findings have been described in recent years, corroborating the idea that external stimuli play a fundamental role in development and stem cell physiology. However, speedy progress is hindered by the lack of adequate and highly efficient tools for the study of cellular mechanisms at the single cell level and within a defined and highly controllable environment.

The work presented in this dissertation focuses on the engineering of ideal techniques for the study of the processes that define stem cell asymmetrical division and fate determination, devising systems that overcome the current limitations of this research field. The first goal of this project was the engineering of a 3D bioprinting system in combination with tissue-specific substrates for the establishment of a biomimetic, highly accurate, three-dimensional cell culture system for the study of extracellular matrix impact on stem cell physiology. Particular focus was posed on the development of an optimal system for the study of the influence of a brain-specific environment on embryonic and neural stem cells’ differentiation potential. The second goal of this project was the optimization of a system for the delivery of single cells or single cell – single beads complexes into three-dimensional substrates to enable the performance of high throughput experiments at the single cell resolution. Particular focus was posed on the development of an optimal system for the study of asymmetrical stem cell division driven by discrete signals.

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DOI

10.25777/h30r-et74

ISBN

9798352694459

ORCID

0000-0002-9154-1667

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