Development and Utilization of a Tissue Engineered Blood Vessel Mimic to Assess the Neointimal Response to Intravascular Stents

Persistent Link:
http://hdl.handle.net/10150/195387
Title:
Development and Utilization of a Tissue Engineered Blood Vessel Mimic to Assess the Neointimal Response to Intravascular Stents
Author:
Cardinal, Kristen O'Halloran
Issue Date:
2007
Publisher:
The University of Arizona.
Rights:
Copyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.
Abstract:
The use of intravascular stents to restore blood flow through restricted vessels in patients with coronary artery disease has become the preferred method for treating a variety of lesion locations and pathologies. As new stent configurations and coatings are developed, a great need exists for high-throughput preclinical evaluation techniques that can interface human tissue with three-dimensional devices. Thus, the goals of this dissertation research were 1) to develop an in vitro blood vessel mimic composed of human cells for preclinical evaluation of intravascular devices, and 2) to utilize the mimic to assess neointimal responses to implanted stents.Experiments in support of these goals were broken into four specific aims. The first aim was to develop an in vitro human blood vessel mimic based on techniques for creating tissue engineered vascular grafts. The second aim was to determine the feasibility of utilizing this vessel mimic for bare metal stent evaluation. The third aim was to use the in vitro vessel to evaluate the cellular response to protein-coated stents. The fourth aim was to take advantage of the ability to control the in vitro vessel environment in order to evaluate the effect of shear rate on the neointimal response to implanted stents.Human blood vessel mimics were created by sodding fat-derived microvascular endothelial cells onto expanded polytetrafluoroethylene grafts and cultivating the vessels in bioreactor systems. This resulted in the development of a luminal lining of endothelial cells with sub-endothelial smooth muscle and mesenchymal cells. Deployment and assessment of bare metal stents within blood vessel mimics supported the feasibility of using the model for stent evaluation, and demonstrated that cell coverage of the device surface could be observed and measured. Protein-modified stents were created by submerging devices in enriched medium, and following implantation in the blood vessel mimic exhibited increased cell coverage and increased tissue thickness as compared with bare metal stents. Finally, an increase in shear rate lead to decreased neointimal coverage of implanted bare metal and modified stents. Overall, this dissertation demonstrates that in vitro human blood vessel mimics can be created and utilized for preclinical device evaluation.
Type:
text; Electronic Dissertation
Keywords:
tissue engineered vascular grafts; stents; endothelial cells
Degree Name:
PhD
Degree Level:
doctoral
Degree Program:
Biomedical Engineering; Graduate College
Degree Grantor:
University of Arizona
Committee Chair:
Williams, Stuart K.

Full metadata record

DC FieldValue Language
dc.language.isoENen_US
dc.titleDevelopment and Utilization of a Tissue Engineered Blood Vessel Mimic to Assess the Neointimal Response to Intravascular Stentsen_US
dc.creatorCardinal, Kristen O'Halloranen_US
dc.contributor.authorCardinal, Kristen O'Halloranen_US
dc.date.issued2007en_US
dc.publisherThe University of Arizona.en_US
dc.rightsCopyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.en_US
dc.description.abstractThe use of intravascular stents to restore blood flow through restricted vessels in patients with coronary artery disease has become the preferred method for treating a variety of lesion locations and pathologies. As new stent configurations and coatings are developed, a great need exists for high-throughput preclinical evaluation techniques that can interface human tissue with three-dimensional devices. Thus, the goals of this dissertation research were 1) to develop an in vitro blood vessel mimic composed of human cells for preclinical evaluation of intravascular devices, and 2) to utilize the mimic to assess neointimal responses to implanted stents.Experiments in support of these goals were broken into four specific aims. The first aim was to develop an in vitro human blood vessel mimic based on techniques for creating tissue engineered vascular grafts. The second aim was to determine the feasibility of utilizing this vessel mimic for bare metal stent evaluation. The third aim was to use the in vitro vessel to evaluate the cellular response to protein-coated stents. The fourth aim was to take advantage of the ability to control the in vitro vessel environment in order to evaluate the effect of shear rate on the neointimal response to implanted stents.Human blood vessel mimics were created by sodding fat-derived microvascular endothelial cells onto expanded polytetrafluoroethylene grafts and cultivating the vessels in bioreactor systems. This resulted in the development of a luminal lining of endothelial cells with sub-endothelial smooth muscle and mesenchymal cells. Deployment and assessment of bare metal stents within blood vessel mimics supported the feasibility of using the model for stent evaluation, and demonstrated that cell coverage of the device surface could be observed and measured. Protein-modified stents were created by submerging devices in enriched medium, and following implantation in the blood vessel mimic exhibited increased cell coverage and increased tissue thickness as compared with bare metal stents. Finally, an increase in shear rate lead to decreased neointimal coverage of implanted bare metal and modified stents. Overall, this dissertation demonstrates that in vitro human blood vessel mimics can be created and utilized for preclinical device evaluation.en_US
dc.typetexten_US
dc.typeElectronic Dissertationen_US
dc.subjecttissue engineered vascular graftsen_US
dc.subjectstentsen_US
dc.subjectendothelial cellsen_US
thesis.degree.namePhDen_US
thesis.degree.leveldoctoralen_US
thesis.degree.disciplineBiomedical Engineeringen_US
thesis.degree.disciplineGraduate Collegeen_US
thesis.degree.grantorUniversity of Arizonaen_US
dc.contributor.chairWilliams, Stuart K.en_US
dc.contributor.committeememberWilliams, Stuart K.en_US
dc.contributor.committeememberHoying, Jamesen_US
dc.contributor.committeememberRiley, Marken_US
dc.contributor.committeememberHossainy, Syeden_US
dc.contributor.committeememberBerman, Scotten_US
dc.identifier.proquest2219en_US
dc.identifier.oclc659747385en_US
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