Date of Award

5-2015

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Legacy Department

Bioengineering

Committee Member

Dr. Dan Simionescu, Committee Chair

Committee Member

Dr. Martine LaBerge

Committee Member

Dr. Ken Webb

Committee Member

Dr. Timothy Williams

Abstract

Heart valve disease often progresses asymptomatically until valve damage has advanced to the point where replacement is unavoidable. Unfortunately, current valve replacements - including mechanical, bioprosthetic and autografts - have serious drawbacks, which often require replacement surgeries or lifelong anticoagulant therapy. The field of tissue engineering aims to overcome these drawbacks by combining scaffolds, stem cells, and chemical and physical stimuli to produce living tissues. The aortic heart valve has a unique structure composed of three discrete layers – fibrosa, spongiosa, and ventricularis - that work together in concert with the resident valvular interstitial cells to maintain a functioning valve. As a result, current tissue-engineered heart valves miss the mark for successful aortic valve replacement in one of two ways: either by being too weak to endure the stresses of the aortic environment or by being insufficiently recellularized and incapable of self-repair. The primary focus of this research was to create a functional heart valve replicating the unique trilayer structure developed by nature. We showed that valves can be modeled from medical imaging data, 3D printed, and used as molds to create patient-specific heart valves. The valve scaffolds supported cell attachment, growth, and proliferation. Porous, dry scaffolds were effectively glued together to form one cohesive trilayer scaffold. These scaffolds resemble the human valve’s unique histoarchitecture. A meta-analysis of literature defined maximum normal stresses and strains experienced by the native valve; providing a target set of mechanical properties to be replicated by the tissue-engineered valve. Increasing porosity and microneedle rolling treatments produced scaffolds with excellent mechanical strength that were more than strong enough to function in physiological conditions. A novel cell seeding technique was developed to rapidly seed porous and microneedle treated fibrous scaffolds; resulting in full-thickness cell seeding. Functional heart valves were made using a crush-mounting system. This system allowed for rapid and reproducible production of valves for in vitro testing. A comparison between mechanical, bioprosthetic, and trilayer valves revealed outstanding hemodynamic performance of trilayer valves. These valves functioned well for three weeks in a heart valve bioreactor. This research produced functional, tissue-engineered heart valves with excellent mechanical and hemodynamic properties.

Share

COinS