Developing a tissue engineered/polyurethane blood vessel using bioengineering techniques

Vein graft failure is a significant issue in cardiovascular disease patients, with restenosis caused by alterations in flow patterns leading to remodelling and disease progression. In the future there will be more demand for replacement of blood vessels with more successful replacements than the veins currently used. 50% of vein grafts fail within 10 years of implantation. This, coupled with an aging population where the frequency of revascularisation is likely to increase, demands the development of alternative vessels that are resistant to such failure. Typically, xenogeneic (animal derived) or fully synthetic implants are used but while lives are saved in these approaches each technique suffers from disadvantages. For example, xenogeneic implants cannot be designed specifically for the patient and both approaches are subject to the immune response and rejection. Synthetic scaffolds have the major advantage in that they are strong and can be designed with dimensions that specifically “fit” the patient. However, as synthetic materials they are subject to severe rejection and patients opting for this approach must take on permanent anticoagulation therapy.

In vivo blood vessels are coated in an epithelial, single cell layer composed of endothelial cells. These cells produce signalling factors that prevent thrombus formation and modulate remodelling of the underlying smooth muscle to maintain vessel patency. Following revascularization however, these systems are prone to failure.

In this project, the ease of processing and good mechanical properties of polyurethanes (PU) will be harnessed to bioengineer the surface to support an endothelium. PUs are the current best available materials for producing synthetic veins but they can suffer thrombus formation and fouling and typically patients require a regime of warfarin. The ultimate aim in the long term is to develop systems that can recruit autologous stem cells from the blood. This means our approach will be to modify the current approved PU material to support endothelial cells as recently published (minor adaptations only will be required as this method was developed for similar epithelial cell types) involving adding alkyl amines. To promote recruitment of stem cells we will also deliver the appropriate cytokines using our novel particulate delivery approach by embedding functional particles within the PU and we will provide signalling factors to ensure that these cells adhere and progress to endothelial cell types.

Objectives
1 Develop a PU support which is engineered to selectively adhere mature primary human endothelial cells
2 Adapt the PU support in objective 1 using bioengineering techniques, including incorporation of appropriate combinations of biological growth factors, to recruit endothelial progenitor cells and promote their differentiation into mature endothelial cells.

The programme offers a number of opportunities to focus on particular aspects of the work: including polymer design and synthesis; use of cardiovascular models and immune-based and molecular biology techniques for cell characterisation. The project will suit candidates with a Masters degree in either chemistry, pharmacy/pharmacology (with a strong basic science component in the degree), biochemistry/biomedical science, bioengineering or biomaterials science. Successful candidates will show a strong desire to learn new areas at the interface of Chemistry and the Biosciences.