Date of Award

5-2016

Document Type

Thesis

Degree Name

Master of Science (MS)

Department

Bioengineering

Committee Member

Dr. Dan Simionescu, Committee Chair

Committee Member

Dr. Aggie Simionescu

Committee Member

Dr. Martine LaBerge

Committee Member

Dr. Ken Webb

Abstract

With an estimated 5 million people suffering from valve disease in the United, valve disease is currently the leading cause of cardiovascular disease. Each year, between 80,000 and 85,000 aortic valve replacements are performed in order to treat the stenotic heart valves. Despite this being a worldwide epidemic, the current valve replacement options that are on the market have distinct limitations. Furthermore, a viable alternative does not exist for the patients that are not candidates for the current treatment methods. Our proposed solution to this epidemic is to create a highly viable injectable scaffold that would allow for the minimally invasive delivery of human adipose-derived stem cells (hADSCs), as well as to provide necessary biological cues for growth and remodeling to the scaffold.

A process was created to create a hydrogel derived from decellularized porcine aortic cusp tissue. The aortic cusp was solubilized using an acid-pepsin solution, neutralized and reformed as a hydrogel structure. This processing was analyzed for effectiveness of decellularization, retention of the extracellular matrix components, scaffold architecture, and cell interaction and viability.

Histology showed proper decellularization while maintaining the components of the extracellular matrix throughout the fabrication process, collagen content analysis provided further evidence of this. Quantitative analysis of H&E sections revealed a highly porous scaffold, conducive to cell migration. Rheological studies revealed shear thinning properties that is advantageous for the ability of the scaffold to be injected. A Live/Dead assay of the scaffold showed an extremely viable scaffold in static conditions, as well as a tendency of the cells to contract and remodel the hydrogel.

Present studies have optimized the technique for creation of the hydrogel, characterized the biological and physical properties of the scaffold, and determined the viability of the scaffold for seeding of hADSCs. These aortic cusp-derived scaffolds provide an environment that mimics the aortic cusp ECM. This research will advance cardiovascular tissue engineering and further aid in the search for the ideal tissue engineered heart valve.

Available for download on Friday, May 01, 2020

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