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Development of a Synthetic External Stent to Prevent Vein Graft and Hemodialysis Access Site Failures

dc.creatorBoire, Timothy Charles
dc.description.abstractHemodialysis is the primary lifeline for nearly half a million Americans with end-stage renal disease (ESRD). Unfortunately, 40 – 60% of these access sites occlude and fail within the first year. This causes significant pain and suffering and makes it more difficult for patients to receive life-saving dialysis treatments. The primary culprit of these failures is neointimal hyperplasia (NH) at the venous anastomosis, as well as negative vascular remodeling processes in the case of arteriovenous fistula maturation failure. Therapeutic approaches have achieved limited success to date, in part because they do not address biomechanical aspects of this process. Along these lines, external stents have exhibited some promise to reduce NH in large animal studies by promoting positive vascular remodeling process such as neovascularization and/or by alleviating biomechanical factors contributing to NH. However, nothing has translated to the clinic thus far, partially owing to inappropriate biomaterial selection and device design. In an effort to address these shortcomings, an external stent comprised of poly(ε-caprolactone)-based shape memory polymers is proposed. The biodegradable material melts around body temperature to provide artery-mimetic mechanical support to the vein in the arteriovenous environment, custom-fitting capabilities, and to facilitate ease-of-use. To determine what pore size and spacing should be applied to the external stent, neovascularization, inflammation, and fibrogenesis were assessed in mice for four candidate designs over the course of 28 days. Histological scoring of tissue responses indicated an upregulation in neovascularization and fibrogenesis relative to nonporous SMPs and microporous ePTFE controls. A CD31-based microvessel detection algorithm identified significantly more neovessels, total vessel area, and microvessel density in the peri-polymer region than non/microporous controls for select pore designs. This promotion in neovascularization coincided with transient upregulation of the pro-inflammatory M1 macrophage phenotype as assessed by immunohistochemical staining of iNOS, suggesting that neovascularization was inflammation-mediated. These results point towards at least one promising design candidate warranting further investigation as an external stent.
dc.subjectexternal stents
dc.subjectShape memory polymers
dc.subjectneointimal hyperplasia
dc.titleDevelopment of a Synthetic External Stent to Prevent Vein Graft and Hemodialysis Access Site Failures
dc.contributor.committeeMemberColleen M. Brophy
dc.contributor.committeeMemberHaoxiang Luo
dc.contributor.committeeMemberBrett C. Byram
dc.contributor.committeeMemberRobert L. Galloway
dc.contributor.committeeMemberDavid Shaffer
dc.type.materialtext Engineering University
dc.contributor.committeeChairCraig L. Duvall

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