Novel Dynamic Bioreactor and PEGDA Hydrogel Scaffolds forInvestigation and Engineering of Aortic Valve Tissues

[摘要] Tissue engineered heart valves (TEHV) will allow clinicians to have a highqualityprosthesis for patients that could eliminate many drawbacks of currently availabletreatments. Although there is great promise for TEHV, the field is still in its infancy;proper scaffolding materials and dynamic culture regimens that produce TEHV suitablefor implantation in the aortic valve (A V) position have not yet been identified. Novelsystems to apply biomechanical stimuli to developing engineered tissues and materialsdevelopment 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 abioreactor system capable of both AV organ culture and biomechanical conditioning ofengineered A V tissues. This work demonstrated that the newly developed bioreactorsystem allows A V to be cultured dynamically in a simple system that scales toaccommodate varying sample sizes. Evaluation of this bioreactor system showed thatdynamic culture of A V maintained normal tissue phenotype for durations of up to sevendays, which is to-date the longest ex vivo maintenance of normal A V tissue phenotype ina 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 flexuralstiffness of the resulting scaffolds could be modulated by varying the formulationparameters chosen, and that valvular interstitial cells embedded and cultured within thesegels (also containing incorporated bioactive moieties) maintained expression of severalcharacteristic phenotypic markers. The thesis also describes studies in which advancediiihydrogel scaffolds were fabricated using anatomically-inspired composite strategies,resulting in scaffolds that possessed unique material properties (anisotropic behavior andaltered bending stiffness) compared to standard single component hydrogels. Thesestudies were the first to show a biphasic, trilayered quasilaminate structure in aphotopolymerized system. Additionally, these studies demonstrated the development ofnew anatomically-inspired patterns of reinforcement that allow hydrogels materialbehavior to more closely mimic tissue. The thesis closes with a description of theimplications of these studies on heart valve tissue engineering and potential futuredirections using these techniques.

[发布机构] Rice University

[效力级别] Biomedical