ORCID
0000-0002-2143-2991
Date of Award
Spring 5-13-2024
Degree Name
Master of Science (MS)
Degree Type
Thesis
Abstract
Hypertrophic Cardiomyopathy (HCM) is an inherited cardiomyopathy disease that affects approximately 1 in 500 to 1 in 200 people. Although abundant evidence has shown that HCM is related to sarcomere genetic mutations, recent research has also revealed that conditions that increase cardiac afterload, like obesity and hypertension, worsen HCM patients’ prognosis. Among research models of HCM, in vitro models that use patient-derived induced pluripotent stem cell (iPSC) differentiated cardiomyocytes are especially promising because the unlimited supply of iPSC can allow many studies to be performed under reproducible conditions. In prior studies of afterload-related phenotypes in HCM and other iPSC-based heart disease models, soft substrates like Polydimethylsiloxane (PDMS) or hydrogels have been used as stiffness matrix. However, these substrates that have constant mechanical properties have the disadvantage of being unable to mimic dynamic changes in cells’ environment that happen in the body as a result of hypertension Thus, magnetorheological elastomers (MREs), which change their stiffness in response to magnetic fields, have been developed as a next-generation substrate for cardiac mechanobiology studies. In this thesis, I characterized how the mechanical properties of MRE vary with respect to substrate geometry, and I am currently in the process of applying these substrates to study how cardiomyocytes and cardiac fibroblasts respond to dynamic stiffness changes. To characterize the mechanical properties and get the highest stiffness range of MRE substrates that we use in our in vitro model, Indentation testing and shear testing were performed on MREs with different dimensions and densities of magnetic-responsive iron particles. For the characterization of the shear modulus, I developed a custom method to replace rheology. I also verified the cytocompatibility of MREs. I am currently using MREs with iPSC-cardiomyocytes and primary cardiac fibroblasts to study how dynamic mechanical loading affects cellular hypertrophy. As a result, Higher magnetic particle doping weight percentage and higher magnetic fields increased MRE stiffness. In contrast, MRE thickness did not affect the shear modulus upon magnetization. Finally, the MREs were proven non-toxic to cells, and representative images of the immunostaining of the cardiomyocytes were acquired. Based on this, we are aiming at doing some preliminary studies on pathological phenotypes of heart disease (e.g. cell hypertrophy) with cardiomyocytes under increased afterload.
Language
English (en)
Chair
Dr. Nathaniel Huebsch
Committee Members
Dr. Guy Genin, Dr. Amit Pathak
Included in
Biomedical Engineering and Bioengineering Commons, Materials Science and Engineering Commons