Degradation of vascular devices (de-vasc): a combined engineering and biological approach

The PI has established a multi-disciplinary team of engineers and biologists with the view to develop novel methodologies to understand the metal-vascular biology interface that is established during stent or graft placement using core underpinning engineering and biological sciences. Expandable metallic structures (typically Co-based or NiTi alloys), known as 'stents', are commonly used to treat Peripheral Arterial Occlusive Diseases (PAOD), a thickening of the artery wall as a result of proliferation of intimal-smooth-muscle cells and Abdominal Aortic Aneurysms (AAA), a weakening of the aorta. PAOD and AAA are commonly treated with braided or a series of overlapping stents resulting in multiple metal-metal contacts being established in-vivo. A thorough understanding of the degradation processes and their role on the remodeling of the vasculature does not exist. This project will fuse contemporary tribocorrosion methods with unique patient specific cell cultures (ie cells obtained from a human donor undergoing vascular intervention) to quantify the synergy between mechanical, corrosion and biological approaches. Novel surface science approaches will then be explored, using the developed methodologies, with the view to further understand and increase the bio-compatibility of future implanted devices. The framework established as part of this grant will bridge the current gap in bio-compatibility testing.The development of an instrument combining mechanical and corrosive processes with clinically relevant biology (all of which are present and interacting in-vivo) will provide an alternative to simplistic static cell culture and complex animal models. This has the potential to significantly reduce R&D costs through more effective screening of prospective technologies as well as reducing the need for animal testing.

This project aims to deliver novel simulation methodologies to understand the impact of vascular device degradation on the biological environment. A research platform with direct clinical and industrial relevance will confer short and long term social and economic benefits. A contemporary thinking around biology-metal interaction will also be developed furthering the current philosophies within academia and beyond. Direct dissemination to key stakeholders will be achieved through the multi-disciplinary network already established as well as publication. Complication rates due to device failure or device-biology interactions is poor compared to other sectors of medicine (for example orthopedics) presenting a clear and timely patient, clinical and industrial need.

Direct and translatable impact to the following is expected;

Patients and care providers - Through enhanced product R&D and a thorough understanding of the device-biology interactions, patients and care providers (including NHS and societal support) will benefit through improved quality of life and reduced patient burden. The UK is facing an increased burden of non-communicable diseases, of which cardiovascular diseases (CD) accounts for 27% of deaths each year and an economic burden estimated to be over £15 billion. With more than 2 million people receiving stents each year and complication rates of up to 40% within 6 month in some cases, the ability to fully understand interfacial reactions and effectively engineer surfaces to reduce current and evident risks will have huge impact for patients and care-providers. When compared to other 'routine' medical procedures (revision rate ~ 10% for hip replacement), the risks associated with angioplasty are significantly higher.

Clinicians - Vascular surgeons and interventional cardiologists using such devices on a daily basis will benefit from an enhanced understanding of the metal-biological interactions ensuring confidence in current and future technologies. By identification of the metal induced cell signalling pathways, effective treatment can be identified, administered and stratified according to patient physiology. Impact in the form of new technologies for the treatment of CD, a reduction in need for future intervention and litigation will also be realised in the medium to long term.

Industry - Methodologies and models developed as part of this proposal will have direct relevance to device manufactures, such as Gore Medical (USA) and Confluent medical (CA, USA), both of which the PI has established links with. Results and methodologies will be used to inform current and future design rules as well as the opportunity to translate any technologies develop as part of the associated PhD project. The use of intravascular devices for treating Atherosclerosis (the build-up of fatty plaques within the innermost layer of the arterial wall) is a well-practiced medical intervention for coronary and peripheral vascular diseases, with over 2 million stent devices being implanted yearly giving rise to an industry estimated to be worth $10.6 billion. Advances this area will allow industries to produce devices with more confidence but also increase market competitiveness.

Effective advances in current technologies will only be made only once the metal-biology interface is fully understood. The methodologies and platforms developed in this project will allow identification of future therapeutic targets as well as surface engineering approaches to mitigate metal induced ISR. The combined mechanical and biological approach proposed as part of this study will allow for high throughput screening of proposed solutions, leading to an accelerated translation to clinical practice and reduced need for animal testing. In the medium/long term the PI and Co-I will actively the project to wider beneficiaries and business communities contributing to the UK's economic growth in vascular medicine.