Date of Award

5-2023

Document Type

Thesis

Committee Chair/Advisor

Will Richardson, Ph.D.

Abstract

The leading cause of death worldwide is cardiovascular disease, responsible for 32% of all global deaths and the leading cause of death for men and women across most racial and ethnic groups in the United States [1]. Between 2016 and 2017, cardiovascular disease cost the U.S. $363 billion in medical costs, research, and healthcare services [1].

Finding new therapies to treat heart disease is very slow and very expensive, which has driven many research companies to develop in vitro screening platforms for testing therapies in cultured cardiac tissue. In Clemson University’s Systems Mechanobiology Lab under the leadership of Dr. Will Richardson, a novel culture chamber is being developed that subjects engineered heart-like tissues to electrical, chemical, and mechanical conditions mimicking heart tissue outside of the human body. This platform can enable high throughput therapy screens for identifying new drug treatments to improve cardiac function across various diseases such as heart attacks, diabetes, and hypertension. Before the novel culture chamber can be used therapeutically, it is necessary to provide evidence that the heart tissue model exhibits statistically similar makeup and behavior to native heart tissue pre- and post-infarction. Otherwise, therapies tested on the platform would not provide an accurate physiological implication for how the therapy would behave within a patient.

Mechanical testing using two different methods was conducted to gather displacement, stress, strain, stiffness, and ultimate force data for engineered tissues in an unwounded state and in a state after being inflicted with a cryogenic wound, mimicking a myocardial infarction. Method 1 utilized the CellScale Biaxial, which conducted displacement control tests and provided inconclusive results. Method 2 utilized a custom 3D-printed mechanical stretcher system that conducted force control tests and provided accurate data for pre-failure stiffness and ultimate 3 tensile force of tissues. The null hypothesis assuming a difference in means of zero was rejected for pre-failure stiffness and ultimate tensile force values post-infarction, with pre-failure stiffness reducing by a factor of 2.0 post-infarction and ultimate tensile force reducing by a factor of 2.3. These results indicate that the lab-grown tissue-engineered constructs behave similarly to in vivo heart tissue which sees reductions in these properties post-infarct due to cellular loss of cardiomyocytes and increased deposition of the less stiff fibrillar collagen. This work contributed to the overarching objective of the Richardson Lab: that the engineered tissue constructs behaved as native tissue does in the process of wound healing from a myocardial infarction, and therefore, that the novel culture chamber would be a valuable indicator of how therapies would react within the heart tissue of an actual patient.

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