Date of Award
12-2011
Document Type
Dissertation
Degree Name
Doctor of Philosophy (PhD)
Legacy Department
Bioengineering
Committee Chair/Advisor
LaBerge, Martine
Committee Member
Nagatomi , Jiro
Committee Member
Simionescu , Dan
Committee Member
Yao , Hai
Committee Member
Langan , Eugene
Abstract
Cardiovascular disease is the leading cause of mortality in The United States and Europe, accounting for approximately half of all deaths. The most common form of cardiovascular disease is atherosclerosis, which is characterized by the formation of fatty atheromatous plaques that can grow to occlude the vessel lumen, thus causing ischemia distal to the occlusion. This is commonly treated using balloon angioplasty, which is usually done in conjunction with the deployment of a stent. Stent deployment helps hold the vessel open following the local injury caused by balloon inflation and prevents elastic recoil and subsequent negative remodeling. Stenting has been shown to significantly reduce restenosis rates from approximately 20-50% without a stent to about 10-30% with stent deployment.
However, restenosis still remains the main cause of long-term stent failure. In basic terms, a balloon angioplasty procedure is a forceful displacement of an atherosclerotic lesion serving to widen the vessel lumen to increase blood flow. This procedure causes stretching of the vessel wall, tears in the atherosclerotic plaques, and general damage to the vessel in turn signaling a complex cascade of thrombosis, inflammation, intimal thickening, and vascular remodeling. Stent deployment also further complicates the immunological response by triggering a foreign body response from the implantation of a biomaterial into the body. When performing an angioplasty procedure, particularly in conjunction with stent deployment, a certain degree of vascular injury is inevitable. However, the initial injury can be further complicated by the body's local reaction to the implanted biomaterial, the severity of which can ultimately dictate the degree of restenosis and subsequently affect procedural success.
The proliferative response of VSMCs to the various afore mentioned stimuli results in the formation of often copious amounts of neointimal tissue, generally known as intimal hyperplasia. The formation of this new tissue, primarily consisting of VSMCs of the synthetic phenotype and their subsequent extracellular matrix, is the sole causation of in-stent restenosis since the stent serves to prevent elastic recoil and negative remodeling.
This doctoral research program is focused on endovascular stent biomaterials science and engineering. Overall, this doctoral project is founded on the hypothesis that smooth muscle cell hyperplasia, as an important causative factor for vascular restenosis following endovascular stent deployment, is triggered by the various effects of stent strut contact on the vessel wall including contact forces and material biocompatibility. In this program, a dynamic in vitro model of a stented blood vessel aimed at evaluating the effect of stent strut material selection, and surface coating on smooth muscle cell response was developed.
The in vitro stented artery model was validated through the proliferation of VSMC in contact with stent struts. Additionally, it was demonstrated that, with respect to known biocompatible materials such as Nitinol and 316L stainless steel, DNA synthesis and alpha-actin expression, as indicators of VSMC phenotype, are independent of stent material composition. Furthermore, hydroxyapatite was shown to be a biocompatible stent surface coating with acceptable post-strain integrity. This coating was shown in a feasibility study to be capable of serving as a favorable drug delivery platform able to reliably deliver locally therapeutic doses of bisphosphonates, such as alendronate, to control VSMC proliferation in an in vitro model of a stented blood vessel. This stent coating/drug combination may be effective for reducing restenosis as a result of VSMC hyperplasia in vivo.
Recommended Citation
Winn, Bradley, "DEVELOPMENT OF A DYNAMIC IN VITRO MODEL OF A STENTED BLOOD VESSEL TO EVALUATE THE EFFECTS OF STENT STRUT MATERIAL SELECTION AND SURFACE COATING ON SMOOTH MUSCLE CELL RESPONSE" (2011). All Dissertations. 862.
https://open.clemson.edu/all_dissertations/862