About the Project
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.
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.
Platt, L.; Kelly, L.; Rimmer, S., Controlled Delivery of Cytokine Growth Factors Mediated by Core-Shell Particles with Poly(Acrylamidomethylpropane Sulphonate) Shells. Journal of Materials Chemistry B 2014, 2, 494-501.
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