Rose, Stacey Loren.
In Vitro Model of Vascular Healing in the Presence of Biomaterials.
Degree: PhD, Biomedical Engineering, 2006, Georgia Tech
Coronary artery stent placement has been a significant advance in the percutaneous treatment of atherosclerotic disease, and tissue engineered vascular grafts may provide a viable alternative to autologous segments for small diameter vessels. However, in-stent restenosis remains an important limitation, and tissue engineered grafts have poor patency and high risk of thrombus formation due to their inability to maintain a confluent, adherent, and quiescent endothelium. While animal models provide insight into the pathophysiology of these situations, elucidation of the relative importance of stent or graft components, hemodynamic factors, and molecular factors is difficult. Very little research has focused on bridging gaps in knowledge concerning blood/biomaterial interactions, blood/endothelial cell interactions, and endothelial cell/smooth muscle cell cross-talk. The work presented within this thesis will do just that. The objective of this thesis research was to elucidate the influence of biomaterial-induced activation of leukocytes on endothelial cell or smooth muscle cell phenotype, as well as endothelial cell/smooth muscle cell cross-talk in co-culture systems. Towards this goal, two complimentary in vitro endothelial cell/smooth muscle cell co-culture models with divergent smooth muscle cell phenotype were developed and characterized. Using these systems, it was found that the presence of more secretory smooth muscle cells (as would be seen in wound healing or disease) in general enhanced endothelial cell activation in response to biomaterial-pretreated monocytes, while the presence of less secretory smooth muscle cells (to model more quiescent smooth muscle cells found in uninjured healthy vessels) suppressed endothelial cell activation in response to biomaterial-pretreated monocytes (and neutrophils to a small degree). Additionally, biomaterial-pretreated monocytes and neutrophils amplified a smooth muscle cell phenotypic shift away from a more quiescent state. It is likely that the compounding effect of secretory smooth muscle cells and biomaterial-activated leukocytes are responsible for altered vascular wound healing upon implantation of stents or vascular grafts. Understanding the specific signals causing these effects, or signals delivered by contractile smooth muscle cells that limit these effects help to provide design criteria for development of devices or grafts capable of long term patency.
Advisors/Committee Members: Dr. Julia Babensee (Committee Chair), Dr. Elliot Chaikof (Committee Member), Dr. Hanjoong Jo (Committee Member), Dr. Michael Sefton (Committee Member), Dr. Robert Nerem (Committee Member), Dr. Suzanne Eskin (Committee Member).
Subjects/Keywords: Biomaterials; Leukocytes; Smooth muscle cells; Endothelial cells; Stents (Surgery); Vascular endothelial growth factors; Biocompatibility; Leucocytes; Regeneration (Biology)
to Zotero / EndNote / Reference
APA (6th Edition):
Rose, S. L. (2006). In Vitro Model of Vascular Healing in the Presence of Biomaterials. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/13955
Chicago Manual of Style (16th Edition):
Rose, Stacey Loren. “In Vitro Model of Vascular Healing in the Presence of Biomaterials.” 2006. Doctoral Dissertation, Georgia Tech. Accessed February 28, 2021.
MLA Handbook (7th Edition):
Rose, Stacey Loren. “In Vitro Model of Vascular Healing in the Presence of Biomaterials.” 2006. Web. 28 Feb 2021.
Rose SL. In Vitro Model of Vascular Healing in the Presence of Biomaterials. [Internet] [Doctoral dissertation]. Georgia Tech; 2006. [cited 2021 Feb 28].
Available from: http://hdl.handle.net/1853/13955.
Council of Science Editors:
Rose SL. In Vitro Model of Vascular Healing in the Presence of Biomaterials. [Doctoral Dissertation]. Georgia Tech; 2006. Available from: http://hdl.handle.net/1853/13955