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NOVEL NANOFIBER-BASED GRAFT FOR HEART VALVE REPLACEMENT

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title
NOVEL NANOFIBER-BASED GRAFT FOR HEART VALVE REPLACEMENT
author
Wang, Rui
abstract
Creating a functional heart valve graft that lasts a lifetime is one of the main targets of cardiovascular tissue engineering. While processed conventional collagen-based heart valves have been used for many years, they eventually fail because of inadequate cell infiltration and insufficient replacement of graft material by tissue remodeling. To overcome the graft failure due to inadequate tissue remodeling and growth, an improved graft material was created by incorporating type I collagen protein with mechanical robust silk fibroin, and hemocompatible synthetic elastic polymer poly(glycerol-sebacate) (PGS). The central hypothesis of this project was: Electrospun grafts created from composites of type I collagen, silk fibroin, and PGS are stable, less thrombogenic and more readily available than the conventionally used collagen-based grafts for aortic heart valve replacement. The aim was to fabricate a graft material that mimicked the composition, structure and mechanical properties of native heart valve tissue, and to promote the formation of an intact non-thrombogenic endothelial cell layer. In this study, an improved heart valve material composed of type I collagen, silk fibroin, and PGS was developed. The homogeneity of blended composites was demonstrated using Fourier transform spectroscopy. Tensile stress, strain, and elastic modulus of the electrospun mats were measured by an Instron mechanical tester. The elastic moduli were between 2.3 - 5.0 Mpa, tensile stresses ranged from 0.8 to 1.5 Mpa, and strains were of 30% - 70%. These values were similar to those reported for native heart valves. Suture retention tests showed a highest 0.32N pull-out force at the single-loop suture site in electrospun mats with 4.5:4.5:1 collagen, silk fibroin and PGS weight ratio (PFC mats). Functional test of PFC mats demonstrated a slow degradation rate as compared to other collagen-based grafts. Cells adhered to and proliferated on PFC mats. Endothelial cells were observed to form tight junctions on the material. Several studies with isolated platelets showed the PFC mats were less thrombogenic in comparison to collagen hydrogels and structurally similar electrospun collagen mats. In summary, this work demonstrated PFC mats provided strong, slowly degradable, and non-thrombogenic grafts that promoted cell adhesion and growth. Therefore, PFC mats could be used as a functional and durable heart valve replacement.
subject
Collagen
Electrospinning
Graft
Heart valve
Poly (glycerol-sebacate)
Silk fibroin
contributor
Wagner, William D. (committee chair)
Levi-Polyachenko, Nicole (committee member)
Mohs, Aaron M. (committee member)
date
2012-06-12T08:36:12Z (accessioned)
2012-12-12T09:30:07Z (available)
2012 (issued)
degree
Biomedical Engineering (discipline)
embargo
2012-12-12 (terms)
identifier
http://hdl.handle.net/10339/37317 (uri)
language
en (iso)
publisher
Wake Forest University
type
Thesis

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