Abstract/Details

Development and utilization of a tissue engineered blood vessel mimic to assess the neointimal response to intravascular stents


2007 2007

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Abstract (summary)

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.

Indexing (details)


Subject
Biomedical research
Classification
0541: Biomedical research
Identifier / keyword
Applied sciences; Blood vessel mimic; Intravascular stents; Neointimal response; Tissue engineering
Title
Development and utilization of a tissue engineered blood vessel mimic to assess the neointimal response to intravascular stents
Author
Cardinal, Kristen O'Halloran
Number of pages
259
Publication year
2007
Degree date
2007
School code
0009
Source
DAI-B 68/04, Dissertation Abstracts International
Place of publication
Ann Arbor
Country of publication
United States
Advisor
Williams, Stuart K.
University/institution
The University of Arizona
University location
United States -- Arizona
Degree
Ph.D.
Source type
Dissertations & Theses
Language
English
Document type
Dissertation/Thesis
Dissertation/thesis number
3259933
ProQuest document ID
304895507
Copyright
Database copyright ProQuest LLC; ProQuest does not claim copyright in the individual underlying works.
Document URL
http://search.proquest.com/docview/304895507
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