Advisory Committee Chair
Palaniappan Sethu
Document Type
Dissertation
Date of Award
2024
Degree Name by School
Doctor of Philosophy (PhD) School of Engineering
Abstract
Despite significant advances in our understanding of the molecular basis of cardiovascular diseases (CVD) and the development of new therapeutics, it remains the number one cause of death worldwide, particularly affecting the aging population. This necessitates the development of models that can more accurately recreate aspects of aging and the interaction of the heart with other organs and systems in the body, including the immune system. Tissue chip models are being increasingly considered for studying cardiac diseases as they can potentially address translational hurdles associated with animal models, yet several challenges hinder their full potential. These include a lack of suitable cell types and culture systems that accurately replicate cardiac hemodynamics. Animal models offer insights into disease progression and therapeutic targets but suffer from low throughput, labor-intensive procedures, and limited applicability due to genetic and physiological differences from humans. This thesis seeks to develop cardiac tissue chip models to mimic cellular, extracellular, hemodynamic, and biochemical environments associated with cardiac physiology to address age-related pathology and study the role of immune cells in the progression of cardiac dysfunction. Chapter 2 focuses on recreating the aging phenotype via the introduction of cellular senescence to model the accumulation of senescent cells within cardiac tissue with age. Chapter 3 focuses on engineering cardiac tissue using recellularized porcine myocardial tissue, which is subjected to pressure and stretch mechanics of the heart to replicate cardiac remodeling. Finally, Chapter 3 focuses on replicating the immune system's interaction with the heart by modeling the recruitment and infiltration of circulating monocyte-derived macrophages following hypoxic insult. Taken together, this thesis project provides new tools and models to study age-related cardiovascular disease, bioengineer human cardiac tissue with physiologically relevant cardiac extracellular matrix, and explore new approaches to model the complex interactions between the heart and the immune system.
Recommended Citation
Budhathoki, Sachin, "Physiologically Relevant Cardiac Tissue Chips For Cardiovascular Disease Modeling" (2024). All ETDs from UAB. 3901.
https://digitalcommons.library.uab.edu/etd-collection/3901