Date of Award
12-2023
Document Type
Dissertation
Degree Name
Doctor of Philosophy (PhD)
Department
Bioengineering
Committee Chair/Advisor
Dr. Bruce Gao
Committee Member
Dr. Will Richardson
Committee Member
Dr. Agneta Simionescu
Committee Member
Dr. Ying Mei
Abstract
Heart Failure, sometimes called Congestive Heart Failure, is a collection of pathological disruptions in which the heart is unable to pump blood properly. It affects over 6 million people in the United States, with the cost-per-patient at approximately $30,000 and the total cost estimated to be $160 billion by 2030. There is no single cause of heart failure, as it can manifest as a varying array of diseases, disorders, and syndromes. However, many of these underlying diseases result specifically from dysregulation of mechanically active cells called cardiac fibroblasts, which play a critical role in the remodeling of the extracellular matrix and provide a feedback mechanism to control force distributions within the myocardium via stiffening or softening the tissue. These forces, generated by cardiomyocytes, are then altered into one of many unique disease states. Cardiac fibrosis stimulates excessive collagen production, stiffening the ECM and resulting in Left Ventricle hypertrophy. Myocardial Infarction results in a localized region of dominant and activated fibroblasts, greatly upregulating ECM production to protect against loss of healthy tissue and disrupting electrical signaling propagation. The underlying mechanisms of fibroblast-mediated matrix remodeling and its effects on cardiomyocyte force generation are critical to our understanding of cardiovascular diseases. We have developed an in vitro 3D wound platform that can recreate biologically relevant mechanical conditions utilizing cardiac fibroblasts and cardiomyocytes. It does this by precisely balancing matrix stiffness properties, cell distributions, and electrical/mechanical stimulation. With the ability to create healthy left ventricular myocardial tissue, we also show the ability to produce diseased tissues that either mimic the mode of injury (MI) or upregulate fibroblast signaling pathways (cardiac fibrosis) to recreate an appropriate model of each pathology. This provides a unique platform that can create and characterize, with high precision, the biological and mechanical condition of diseased myocardial tissue for use in clinical or drug development applications.
Recommended Citation
Heywood, Jonathan, "An In Vitro Platform to Characterize Myocardial Wound Remodeling" (2023). All Dissertations. 3462.
https://open.clemson.edu/all_dissertations/3462