Date of Award
12-2022
Document Type
Dissertation
Degree Name
Doctor of Philosophy (PhD)
Department
Bioengineering
Committee Chair/Advisor
Dr. David Karig
Committee Member
Dr. William J. Richardson
Committee Member
Dr. Jordon Gilmore
Committee Member
Dr. Ken Webb
Abstract
Heart failure is a broad pathology manifestation categorized by an inability of the heart to successfully pump blood throughout the vast vessel network of the body. Within the United States, heart failure is projected to increase by approximately 46% from 2012 to 2030. Modalities of heart failure are generally related to wall mechanics that are impacted following myocardial infarction events. Interplay exists between the wall mechanics, responding cell populations, and the spatial heterogeneities in the resultant scar. This interplay directs the myocardium towards heart failure modalities governed by overly stiff or compliant states. It is essential to elucidate details underlying the progression, maturation, and remodeling of the collagenous infarct scar to uncover therapeutic avenues and improve outcomes. We developed in vitro platforms that enable these desired insights into infarct progression. Our first platform generates continuous collagen gels possessing spatial fiber alignment heterogeneity utilizing a cost-efficient magnetic microsphere methodology. Spatial heterogeneities in the fiber architecture and cell response were evaluated. The second platform mechanically and electrically stimulates engineered heart tissue constructs and enables the evaluation of spatial heterogeneities in construct mechanics following a simulated infarction. Additionally, to avoid losing sight of the in vivo reality, we evaluated the interplay of the cellular detection of mechanics and spatial strain distributions throughout an infarcted myocardial wall. Histologically evaluated mechanosensor intensities were correlated to in vivo strain data collected via ultrasound imaging of the myocardium of a murine infarction animal model.
Recommended Citation
Potter, Michael, "Investigating Spatial Heterogeneity In Myocardial Wound Environments To Improve Therapy" (2022). All Dissertations. 3187.
https://tigerprints.clemson.edu/all_dissertations/3187
Author ORCID Identifier
0000-0001-8557-9629