Thesis

Development of novel antioxidant drug-free coronary artery stent coatings

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Awarding institution
  • University of Strathclyde
Date of award
  • 2023
Thesis identifier
  • T16620
Person Identifier (Local)
  • 201774126
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Department, School or Faculty
Abstract
  • Drug eluting stents have significantly improved patient outcomes since their introduction to widespread clinical practice in the early 2000s, but significant complications remain including restenosis and thrombosis. These issues become particularly apparent in the late and very late stages after stent placement (>12 & 24 months), although the cause can be linked to the initial response of the vessel to stenting and failure to achieve complete re-endothelialisation. Oxidative stress offers a target for controlling the early vessel healing response and dampening pro-atherogenic inflammatory stresses. Oxidation and activation of the enzyme Ca2+/calmodulin-dependent protein kinase II (CaMKII), a pivotal molecular switch in the transition between heath and disease in the cardiovascular system, may play a crucial role in vessel pathology following stenting. Inducing a pro-healing response by targeting oxidation and specifically CaMKII oxidation represents a novel approach that may thus improve patient outcomes. Due to their redox-sensitive chemistry, conducting polymers may be capable of acting as scavengers of reactive oxygen species (ROS) and eliciting antioxidant benefit. Polypyrrole (PPy) presents a suitable coating due to its established biocompatibility and ability to be generated using electropolymerisation. This study aimed to reliably generate uniform PPy coatings by electropolymerisation and determine their ROS scavenging capacity. Furthermore, this study explored the response of vascular cells to PPy coatings and their effect on ROS generation and CaMKII activation. In this study, electropolymerisation was found to be effective at generating PPy films on stainless steel wires and strips under potentiostatic and galvanostatic conditions. Scanning electron microscopy, cyclic voltammetry and electrical impedance spectroscopy were used to show that 1.3 V applied voltage and 0.5 mA maintained current were optimal for generating PPy-coated wires over 10 minutes. All PPy coatings generated by electropolymerisation were found to demonstrate high DPPH (2,2-diphenyl-1-picrylhydrazyl) scavenging capacity, with coatings generated potentiostatically at 1.3 V also exhibiting significant scavenging activity against biologically relevant ROS. PPy coatings were found to allow endothelial cell attachment and proliferation. The benefit of PPy on ROS generation and CaMKII activation was more limited, with no significant reduction in ROS generation in PPy-attached human coronary artery endothelial cells (HCAEC) compared with stainless steel and tissue culture plastic (TCP)-attached cells, but PPy-coated strips generated galvanostatically at 1 mA were found to significantly decrease TNFα (tissue necrotic factor-alpha)-stimulated CaMKII oxidation in HCAECs (TCP: 1.93±0.19, vs. 1 mA: 0.75±0.06; mean fold-change c.f. unstimulated TCP attached-HCAECs, two-way ANOVA with post-hoc Sidak, p<0.05, n=4). The results of this study establish the potential benefit of PPy as a novel antioxidant and therefore demonstrate the need for continued investigation of this material in coronary artery stent applications.
Advisor / supervisor
  • McCormick, Christopher
  • Currie, Susan
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Note
  • This thesis was previously held under moratorium from 12/05/2023 until 12/05/2026.
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