Effects of a novel biodegradable stent on biomarkers of vascular health in a pre-clinical large animal model

This project is a collaboration between Manchester Metropolitan University and Manchester University NHS Foundation Trust to interrogate the different effects on vascular health using a novel bioabsorbable stent compared to a conventional stent in an aging sheep model. The student will work with histological samples, serum analysis and will employ other cell and molecular biology techniques.
Specific Requirements of the Project
The student will conduct an interdisciplinary project at the interface between molecular and cellular signaling, cell culture and biochemical analysis as part of an investigative pre-clinical trial. The project will use a variety of imaging, cell and molecular biology, and biochemical techniques and offers an excellent opportunity to work in collaboration with interventional cardiolologists, biologists and mathematicians as part of a cross-disciplinary research group.

• The candidate must hold a good BSc (Hons) degree (2:1 or above) in a Biomedical Science/Biology discipline. An MSc/MRes in a relevant discipline is desirable.
• Some background knowledge in cardiovascular disease. Laboratory experience in cell and molecular biology is desirable, but training can be provided.
• Good organisational and IT skills, and time management.
• Flexibility with regard to working hours. (The work may involve lengthy preparative procedures. 35 hours per week is a minimal requirement.)
• Ability to work in a team, to show enthusiasm, possess self-motivation and embrace hard work.
Project Aims and Objectives
Clinical Problem: Endovascular stenting is a well established treatment for narrowed or weakened coronary and peripheral vessels where a mechanical device is inserted to hold open an artery. The restenosis and plaque development arises because of the proliferation of smooth muscle cells, the impaired healing of the endothelial layer, and the presence of systemic and vascular inflammation, triggered by the unique and highly dynamic mechanical environment, which is not considered in current stent design and consequently results in mechanical damage to the artery and stent.

The prevalence of late thrombosis remains unacceptably high, and identifying patients who are at most risk of a major adverse coronary event (MACE) remains an unmet clinical challenge, and could be prevented by improved endothelial regeneration following vascular injury.

AIM: The study will compare angiographic, OCT, mechanical metrics, histology, the inflammatory signature and clinical outcomes through use of 2 distinct novel-biodegradable stents in an aging sheep model.

Experimental Design:
A total of 10 sheep will undergo percutaneous coronary intervention (PCI) using two biodegradable stents per sheep, and blood will be taken prior to PCI and post surgery.

Any MACE will be monitored, cardiac death, myocardial infarction, and stent thrombosis, target lesion revascularisation , and risk of all-cause mortality.

Quantitative coronary angiography and OCT imaging will be performed pre-stent and post-implantation at 5, 14, 28, 42 days and 5 months. Two sheep will be culled at 5 days (for light microscopy (LM) and scanning electron microscopy (EM), one sheep at 14 days (scanning EM), 2 sheep at 28 days, 1 sheep at 42 days and 4 sheep at 5 months. Stented segments will be excised, formalin-fixed, and sectioned for morphometry and light microscopy. Remaining stents will be examined by TEM and SEM. Serum samples will be collected before stent implantation, then 24 hours later, and at each of the six time points following the procedure for suspension array analysis.

Any MACE will be monitored, (cardiac death, myocardial infarction, and stent thrombosis, target lesion revascularisation (TLR), target vessel revascularisation (TVR), and risk of all-cause mortality). We expect the stents to be tolerable and clinically safe.

The objective of this study is to evaluate the relationship between inflammatory markers interleukin (IL)-1β, IL-6, IL-8, IL-10, tumor necrosis factor α (TNF-α), transforming growth factor β (TGF-β), highly sensitive C-reactive protein (CRP), coronary flow velocity profiles and the biomechanical determinants in the development of arterial restenosis six months after PCI and establish if a biodegradable stent is more effective in attenuating vascular damage
Closing date / Interview / Start dates
Deadline for receipt of applications:
12-11-2018

Interview date:
03-12-2018

When is the student expected to start?
January 2019