Date of Award

2020

Document Type

Open Access Dissertation

Degree Name

Doctor of Philosophy in Biomedical Engineering (PhD)

Administrative Home Department

Department of Biomedical Engineering

Advisor 1

Smitha Rao

Committee Member 1

Megan Frost

Committee Member 2

Orhan Soykan

Committee Member 3

Jeremy Goldman

Abstract

The mechanotransduction of cells is the intrinsic ability of cells to convert the mechanical signals provided by the surrounding matrix and other cells into biochemical signals that affect several distinct processes such as tumorigenesis, wound healing, and organ formation. The use of biomaterials as an artificial scaffold for cell attachment, differentiation and proliferation provides a tool to modulate and understand the mechanotransduction pathways, develop better in vitro models and clinical remedies. The effect of topographical cues and stiffness was investigated in fibroblasts using polycaprolactone (PCL)- Polyaniline (PANI) based scaffolds that were fabricated using a self-assembly method and electrospinning. Through this method, scaffolds of different topography and stiffness were fabricated with similar surface chemistries. The effect of scaffold morphologies on the cells were investigated. PCL scaffolds of three distinct morphologies- honeycomb, aligned and mesh were used with similar surface chemistry to investigate the changes in cell behavior of breast, renal, lung and bladder cancer to the physical cues. Selective adhesion and localization of cells to specific morphologies were determined. In order to demonstrate the scaffold as a source of biochemical signals, ManCou-H, capable of targeting the fructose-specific glucose transporter GLUT5 was electrospun with the scaffolds of different morphologies. The PCL scaffolds were used as the backbone to release ManCou-H and changes in protein expression and metabolic activity was characterized. The findings made available through this research will help in the design of better cell-specific in vitro model systems to better understand cellular responses to clinical therapies, assess cell response to specific mechanical and chemical cues.

Available for download on Friday, August 20, 2021

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