| Summary: | Tissue engineered heart valves (TEHV) will allow clinicians to have a highquality
prosthesis for patients that could eliminate many drawbacks of currently available
treatments. Although there is great promise for TEHV, the field is still in its infancy;
proper scaffolding materials and dynamic culture regimens that produce TEHV suitable
for implantation in the aortic valve (A V) position have not yet been identified. Novel
systems to apply biomechanical stimuli to developing engineered tissues and materials
development and characterization will be necessary to progress towards an aortic TEHV.
This thesis work aimed to address these issues in a parallel manner.
The thesis begins by describing the design and physical characterization of a
bioreactor system capable of both AV organ culture and biomechanical conditioning of
engineered A V tissues. This work demonstrated that the newly developed bioreactor
system allows A V to be cultured dynamically in a simple system that scales to
accommodate varying sample sizes. Evaluation of this bioreactor system showed that
dynamic culture of A V maintained normal tissue phenotype for durations of up to seven
days, which is to-date the longest ex vivo maintenance of normal A V tissue phenotype in
a dynamic bioreactor system.
This thesis work also investigated the suitability ofpoly(ethylene glycol)
diacrylate hydro gels to be used as a TEHV scaffold. These studies showed that flexural
stiffness of the resulting scaffolds could be modulated by varying the formulation
parameters chosen, and that valvular interstitial cells embedded and cultured within these
gels (also containing incorporated bioactive moieties) maintained expression of several
characteristic phenotypic markers. The thesis also describes studies in which advanced
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hydrogel scaffolds were fabricated using anatomically-inspired composite strategies,
resulting in scaffolds that possessed unique material properties (anisotropic behavior and
altered bending stiffness) compared to standard single component hydrogels. These
studies were the first to show a biphasic, trilayered quasilaminate structure in a
photopolymerized system. Additionally, these studies demonstrated the development of
new anatomically-inspired patterns of reinforcement that allow hydrogels material
behavior to more closely mimic tissue. The thesis closes with a description of the
implications of these studies on heart valve tissue engineering and potential future
directions using these techniques.
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