Date of Award

2025-05-01

Degree Name

Master of Science

Department

Biomedical Engineering

Advisor(s)

Binata Joddar

Second Advisor

Wilson Poon

Abstract

This project aimed to develop a tissue-on-a-chip platform for studying Parkinson's Disease (PD) using dopaminergic (DA) neurons. PD is a neurodegenerative disorder characterized by progressive loss of DA neurons, leading to involuntary movements and other symptoms. Early diagnosis and deeper understanding of PD pathogenesis are crucial for improving disease management and patient outcomes. To model PD in vitro, this research utilized human-induced pluripotent stem cell (hiPSC)-derived neural progenitor cells (NPCs) cultured on electrospun (ES) polycaprolactone (PCL) scaffolds. Given PCL's hydrophobicity, ECM-based biomaterial coatings, including Cell Basement Membrane (CBM) proteins, Matrigel, and Fibrin, were explored to enhance NPC adhesion, differentiation, and maturation into DA neurons. Based on prior research, we hypothesized that fibrin-coated scaffolds would best support neural differentiation and maturation. To evaluate scaffold properties, both uncoated and coated, were characterized using Scanning Electron Microscopy (SEM), Transmission Electron Microscopy (TEM), Fourier Transform Infrared Spectroscopy (FTIR-ATR), and Dynamic Mechanical Analysis (DMA). NPCs were seeded onto the scaffolds, differentiated, and matured into DA neurons. Their differentiation was assessed via immunocytochemistry targeting Tyrosine Hydroxylase (TH) to confirm DA neuronal marker expression, SEM to examine morphological changes, and electrophysiology through microelectrode array (MEA) techniques to record neuronal firing activity. Results from this study demonstrated enhanced neurite extension, increased TH expression in cells differentiated atop diluted fibrin-coated samples, and active electrical firing activity in the differentiated cells. This comprehensive investigation highlights the potential of fibrin-coated ES scaffolds as a promising approach in neuronal tissue engineering and PD research.

Language

en

Provenance

Received from ProQuest

File Size

54 p.

File Format

application/pdf

Rights Holder

Salma Paulina Ramirez

Included in

Biomedical Commons

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