About the project:
Chronic kidney disease (CKD) is a serious condition that poses a significant burden on global healthcare systems due to its increasing incidence and high treatment costs. As a result, it is one of the leading causes of morbidity and mortality globally1.
When treating end-stage CKD, a kidney transplant or haemodialysis is required. Unfortunately, there is a global shortage of kidney donors, so most patients rely on haemodialysis. This procedure involves diverting the patient's blood to an external dialysis machine via an arteriovenous (AV) graft. However, current AV grafts require 2-3 weeks to heal2 and do not fully integrate with adjacent tissues, leading to complications such as haematomas, leaks, infection, and thrombosis3. Consequently, there is an urgent need to improve current AV grafts with respect to anti-thrombosis, anti-infection, and biocompatibility properties.
This interdisciplinary PhD project, conducted in partnership with the University of Southern Denmark, aims to explore how the AV graft can be integrated with surrounding tissue to anchor the graft and prevent defensive physiological reactions. An extracellular matrix-like coating constitutes an optimal substrate for cell/material interaction. Different extracellular matrix compositions can also provide various cues to cells and tissues. To create a fully biological graft/tissue bio-interface, we will use silicone-based interpenetrating polymer network (IPN) grafts4,5, coated with an extracellular matrix biomimetic. We will study the integration of epithelial and smooth muscle cells and analyse potential cytotoxic effects in adhering cells including changes in gene expression.
Additionally, the host response to implanted materials is a highly regulated process that impacts the graft functionality and clinical outcomes. AV grafts often elicit a chronic foreign body reaction with resulting fibrosis. Previous studies suggest that an extracellular matrix hydrogel coating can decrease the intensity of physiological responses6, although the exact mode of action is not yet clear. Since macrophages play a crucial role in the development of the inflammatory response to biomaterials, this project will explore macrophage polarisation in vitro.
Complementing the in vitro work, in vivo trials are planned together with the University of Southern Denmark in which the material will be implanted under the skin in mice or rats followed by analysis of integration and inflammation responses.
The outcomes of this project will lead to the optimised composition and maturation of the AV graft by allowing accelerated attachment and interaction of cells, leading to the full tissue integration of the graft in a safe biocompatible manner.
Academic Environment:
The School of Chemical Engineering at Birmingham is one of the three largest centres for the postgraduate education of chemical engineers in the UK. We have pioneered development and research in rapidly expanding new areas such as pharmaceuticals and bioproducts, food processing, energy research and healthcare technologies. The Healthcare Technologies Institute was established in 2018 and has received over £34m of research funding, bringing together leading experts from a variety of disciplines, including chemical engineering, biomedical science, computer science, applied mathematics, chemistry, and physics, with the aim to lead regional innovation across the West Midlands in the field of medical technologies.
Applications should be made through the University of Birmingham’s online applications system. Please include a copy of your CV, a cover letter outlining your research interests and previous experience, and the names and addresses of two referees.
Continue with Facebook
