Advanced coatings to improve the bio-integration of vascular grafts

Vascular grafts have been for 50 years the established practice for the replacement of any diseased segments of aorta from the aortic valve to the iliac bifurcation. Two of the main clinical problems of these medical devices are the risk of infection and risk of thrombotic stenosis due to the material's pro-thrombogenic activity which typically lead to new surgeries. It has been hypothesised that the lack of endothelisation of these grafts could significantly contribute to these problems. This project will develop new bioactive coatings that can be applied on existing grafts to maximize the process of endothelisation and develop next generation of vascular grafts. The project will be developed between the University of Glasgow and Terumo Aortic - a world leader in the fabrication of vascular grafts. This is a multidisciplinary project that will work at the interface between materials and cells. The project will implement state-of-the art coating techniques to present bioactive molecules that promote the growth of endothelial cells on the wall of the vascular graft. The project will allow the student to develop skills in a number of experimental techniques including characterization of functional biomaterials, atomic force microscopy, confocal microscopy and cell and molecular biology at the interface between biomaterials and cells. It will also give them significant industrial exposure through close collaboration with and placements at the company.

Humanised, 3D tissue models are finding interest due to current overly-simplified immortal cell lines and non-human in vivo models providing poor prediction of drug safety, dosing and efficacy; 43% of drug fails are not predicted by traditional screening and move into phase I clinical trials1. Phase I sees a 48% success rate, phase II a 29% success rate and phase III a 67% success rate [1]. The drug development pipeline is pressurised due to adoption of high throughput screening / combinatorial libraries. However, while R&D spend has increased to meet this growing screening programme, success, measured by launched drugs, remains static [2]. This poor predictive power of the >1 million animals used in the UK each year drives the 12-15 year, £1.85B pipeline, for each new drug launch [3]. Contract research organisations (CROs) are also similarly hit by these problems.

Drive to reduce animal experimentation in toxicology and outright banning of animal testing for e.g. cosmetics in the UK has driven companies to outsource or to adopt the limited number of regulator approved NAT models for e.g. skin [4,5].

Another key area that uses 3D tissues is the field of advanced therapeutic medicinal products (ATMPs), i.e. tissue engineering/regenerative medicine. Regulation is a major ATMP bottleneck. It is thus noteworthy that regulators, such as the UKs Medicines and Healthcare Products Regulatory Agency (MHRA), are receptive to the inclusion of NAT-based data in investigative medicinal product dossiers [6].

The lifETIME CDT will directly address these issues through nurturing of a cohort training not only in the research skills required to conceive and design new NATs, but also in skills based on:

- GMP and manufacture.
- Commercialisation and entrepreneurship.
- Regulation.
- Drug discovery and toxicology - a focus on the end product.
- Policy.
- Public engagement.

Our NAT graduate community will impact on:

- Pharma - access to skills that develop tools to unlock their drug discovery and testing portfolios. By helping train graduates who can create and deploy NATs, they will increase efficiency of drug development pipelines.

- ATMP manufacturers - the same skills and tools used to deliver NAT innovation will help to deliver tissue engineered / combination product ATMPs.

- CROs - access to skills to create platform tools providing more sophisticated approaches to the diverse research challenges they face.

- Catapult Centres - access to skills that provide innovation that can be deployed across the broader healthcare sector.

- Regulatory agencies e.g. MHRA - better education for the next generation of scientists on development of investigational new drug / medicinal product dossiers to speedup approvals.

- Clinicians and NHS - access to more medicines more quickly through provision of highly skilled scientists, manufacturers and regulators. NATs will help drive the stratified/personalised medicine revolution and understand safety and efficacy parameters in human-relevant tissues. Clinicians will also benefit from development of ATMP-based regenerative medicine.

- Patients - benefit from skills for faster and more economically streamlined development of new medicines that will improve lifespan and healthspan.

- Public and Society - benefit from the economic growth of a thriving drug development industry. Benefits will be direct, via jobs creation and access to wider and more targeted healthcare products; and indirect, via increased economic benefit of patients returning to work and increased tax revenues, that in turn feed back into the healthcare systems.


[1]. Cook. Nat Rev Drug Discov 13, 419-431 (2014).
[2]. Pammolli. Nat Rev Drug Discov 10, 428-438 (2011).
[3]. DiMasi. Health Econ 47, 20-33 (2016).
[4]. Cotovio. Altern Lab Anim 33, 329-349 (2005).
[5]. Kandarova. Altern Lab Anim 33, 351-367 (2005).
[6]. https://goo.gl/i6xbmL