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Title: Vascular endothelial growth factor-eluting, polymer-coated, coronary stents : an in vitro and in vivo evaluation
Author: Swanson, Neil M. G.
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2003
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Introduction: Percutaneous intervention (PCI) is complicated by restenosis, stent thrombosis and delayed endothelial recovery at the PCI site. One approach to reduce these complications is to deliver potent agents directly to the PCI site. This local drug delivery can be achieved by absorbing drugs into a polymer coating applied to the stent itself. Vascular Endothelial Growth Factor (VEGF) has been shown to accelerate the recovery of endothelium over a stent, reducing intimal hyperplasia and thrombosis. It has not previously been delivered bound onto the stent itself. VEGF-eluting stents were tested in vitro and in a rabbit model. Original Hypothesis: Polymer coated stents may absorb and gradually release Vascular Endothelial Growth Factor. This released VEGF may reduce the stent complications of thrombosis and neointimal hyperplasia, primarily by accelerating the recovery of denuded endothelium. This was tested in vitro and in an animal model. Methods: Studies were performed to determine optimum stent loading with VEGF, which was radiolabelled. Loaded stents were perfused and the drug release kinetics measured. VEGF's potential to stimulate growth was assessed in endothelial cell culture. The VEGF-eluting stents were placed in rabbit iliac arteries and their effects on flow through the artery and acute platelet deposition were determined. Other animals were used to show longer-term effects on endothelial recovery and stent thrombosis (at 7 days) and intimal hyperplasia (at 28 days). Results: 21,7pg of VEGF was absorbed. This was released with a bi-exponential release curve with 20% remaining at 9 days. In arterial tissue, 11% of the VEGF was detectable in the tissue at 24hr. VEGF-eluting stents stimulated endothelial cell growth by 11% over 5 days, with effects that were sustained beyond the initial rapid VEGF release. The animal studies showed a trend (p=0.07) towards reduced platelet deposition early after PCI, with reduced thrombus formation at 7 days (Omg in VEGF stents vs. 12.5mg in controls). No benefit of VEGF stents was seen on the re-endothelialisation process or on intimal hyperplasia. Conclusions: VEGF can be delivered by polymer-coated stents. Prolonged drug release to the injured vessel wall can be shown. However, VEGF did not fulfil the potential suggested by previous work and by the cell culture experiments when tested in vivo. It did appear to reduce thrombus formation and so may have potential benefits in clinical practice as a stent-based therapy.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (M.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available