The characterization of the microstructure of the aortic valve for tissue engineering applications

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dc.contributor.advisorGrande-Allen, K. Janeen_US
dc.contributor.committeeMemberWest, Jennifer L.en_US
dc.contributor.committeeMemberJacot, Jeffrey G.en_US
dc.contributor.committeeMemberKillian, Thomas C.en_US
dc.creatorTseng, Huberten_US
dc.date.accessioned2013-09-16T16:57:25Zen_US
dc.date.accessioned2013-09-16T16:57:40Zen_US
dc.date.available2013-09-16T16:57:25Zen_US
dc.date.available2013-09-16T16:57:40Zen_US
dc.date.created2013-05en_US
dc.date.issued2013-09-16en_US
dc.date.submittedMay 2013en_US
dc.date.updated2013-09-16T16:57:41Zen_US
dc.description.abstractThe aortic valve maintains unidirectional blood flow between the left ventricle and the systemic circulation. When diseased, the valve is replaced either by a mechanical or a bioprosthetic heart valve, that carry issues such as thrombogenesis, long term structural failure, and calcification, necessitating the development of more structurally and biologically sufficient long-term replacements. Tissue engineering provides a possible avenue for development, combining cells, scaffolds, and biochemical factors to regenerate tissue. The overall goal of this dissertation was to create a foundation for the rational design of a tissue engineered aortic valve. The novel approach taken in this thesis research was to view each of the three leaflets as a laminate structure. The first three aims consider the leaflet as a laminate structure comprising of layers of collagen, elastin, and glycosaminoglycans (GAGs). In the first aim, the effect of GAGs on the tensile properties and stress relaxation in the leaflet was investigated, by removing GAGs through increasing amounts of hyaluronidase. A decrease in GAGs led to significantly higher elastic moduli, maximum stresses, and hysteresis in the leaflet. In the second aim, the 3D elastic fiber network of the leaflet was characterized using immunohistochemistry and scanning electron microscopy. This structure was found to have regionally varying thicknesses and patterns. In the third aim, a novel hydrogel-fiber composite design was proposed to match the anisotropy of the leaflet. This composite composed of aligned electrospun poly(ε-caprolactone) (PCL) within a poly(ethylene glycol) diacrylate (PEGDA) matrix. Surface modification and embedding of the PCL did not significantly alter the anisotropy or strength of the underlying PCL scaffold, providing the basis for an anisotropic, biocompatible scaffold. In the last aim, a novel co-culture model was designed using magnetic levitation as a layered structure of valvular endothelial cells and interstitial cells. This technique was used to create co-culture models within hours, while maintaining cell phenotype and function, and inducing extracellular matrix formation, as shown by immunohistochemical stains and their gene expression profiling. The overall result of this dissertation is a clearer understanding of the layered structure-function relationship of the aortic valve, and its application towards heart valve tissue engineering.en_US
dc.format.mimetypeapplication/pdfen_US
dc.identifier.citationTseng, Hubert. "The characterization of the microstructure of the aortic valve for tissue engineering applications." (2013) Diss., Rice University. <a href="https://hdl.handle.net/1911/72051">https://hdl.handle.net/1911/72051</a>.en_US
dc.identifier.slug123456789/ETD-2013-05-505en_US
dc.identifier.urihttps://hdl.handle.net/1911/72051en_US
dc.language.isoengen_US
dc.rightsCopyright is held by the author, unless otherwise indicated. Permission to reuse, publish, or reproduce the work beyond the bounds of fair use or other exemptions to copyright law must be obtained from the copyright holder.en_US
dc.subjectAortic valveen_US
dc.subjectTissue engineeringen_US
dc.subjectBiomechanicsen_US
dc.subjectHeart valvesen_US
dc.subjectValvular interstitial cellen_US
dc.subjectValvular endothelial cellen_US
dc.subjectGlycosaminoglycansen_US
dc.subjectElastic fibersen_US
dc.subjectPolyethylene glycolen_US
dc.subjectPolycaprolactoneen_US
dc.subjectMagnetic levitationen_US
dc.subjectCo-culturesen_US
dc.titleThe characterization of the microstructure of the aortic valve for tissue engineering applicationsen_US
dc.typeThesisen_US
dc.type.materialTexten_US
thesis.degree.departmentBioengineeringen_US
thesis.degree.disciplineEngineeringen_US
thesis.degree.grantorRice Universityen_US
thesis.degree.levelDoctoralen_US
thesis.degree.nameDoctor of Philosophyen_US
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