Date of Award

Summer 2025

Document Type

Open Access Dissertation

Department

Chemistry and Biochemistry

First Advisor

Jie Li

Abstract

The interaction between biomaterials and cellular environments is pivotal in advancing tissue engineering and regenerative medicine. This dissertation explores the influence of TMV-RGD1, a functionalized viral scaffold, on the aggregation and differentiation of P19 embryonal carcinoma cells, aiming to create novel bioactive surfaces that direct cellular behavior. By leveraging the structural and biochemical properties of TMV-RGD1, this work presents a multifaceted approach to studying cell-material interactions, focusing on aggregation mechanisms, gene expression, and potential applications in biomaterial design. Chapter 1 provides a comprehensive review of extracellular matrix (ECM) molecules and their critical roles in regulating cell behavior. The chapter highlights the challenges of replicating in vivo ECM effects in vitro and sets the stage for using TMV-RGD1 as an innovative biomaterial. TMV-RGD1 integrates mechanical and biochemical cues, positioning it as a promising tool for influencing stem cell fate. Chapter 2 delves into the experimental study of P19 cell aggregation on TMV-RGD1 surfaces, comparing the results with control groups, including TMV-WT and traditional ECM components. The chapter discusses the conditions under which TMV-RGD1 enhances cell aggregate formation, such as varying cell densities and serum concentrations. Results indicate that TMV-RGD1 promotes more robust aggregation compared to other surfaces, suggesting its role in facilitating integrin-mediated cell adhesion. Chapter 3 focuses on the comparative analysis between TMV-RGD1 and retinoic acid (RA) in guiding the differentiation of P19 cells. RNA-seq data provides insights into the distinct transcriptional changes induced by both treatments, emphasizing the differences in gene expression profiles and pathways. The findings demonstrate that TMV-RGD1 offers a unique differentiation trajectory, contributing to the understanding of its potential as a differentiation-inducing scaffold. Chapter 4 shifts to the broader context of hydrogen sulfide (H₂S)-releasing biomaterials and their implications in cellular behavior and tissue engineering. This chapter reviews recent advances in H₂S delivery systems and their applications in modulating cellular responses, such as wound healing and anti-inflammatory effects. Integrating H₂S-releasing mechanisms into biomaterials like TMV-RGD1 could offer new possibilities for therapeutic applications. The findings presented in this dissertation highlight the potential of TMV-RGD1 as a multifunctional scaffold in tissue engineering. By combining experimental and theoretical approaches, this work contributes to the broader understanding of cell-material interactions, offering new strategies for designing bioactive surfaces that can regulate cell fate and behavior.

Rights

© 2025, Jingyu Fan

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Available for download on Monday, May 31, 2027

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