EPICSTENT · Antibody-functionalised cardiovascular stents for improved biocompatibility and reduced restenosis

Antibody-functionalised cardiovascular stents for improved biocompatibility and reduced restenosis

Overview of project area Cardiovascular disease (CVD) is the main cause of mortality in European countries. About half of all deaths from cardiovascular diseases are due to coronary artery disease, which occurs when the coronary arteries become hardened and narrowed due to the build-up of plaques on their inner walls or lining (atherosclerosis), leading to reduced blood flow. The long-term prognosis for patients is also poor, with over 30% re-hospitalised within one year of initial presentation, at an estimated overall cost to the EU economy of €192 billion/year. One of the main treatments of atherosclerosis is angioplasty, where a balloon-tipped catheter is used to re-open the vessel and a stent is deployed to provide radial strength and keep the vessel open to avoid restenosis (re-narrowing). After deployment, complete reendothelialization of the deployed stent is critical to avoid thrombosis, or stent re-blocking. This typically takes 3-4 months in the case of bare metal stents (BMS) but considerably longer for drug-eluting stents (DES). Project objectives The objectives of the work programme were to: • foster exchange of knowledge and scientific capabilities between the European medical devices and biomaterials industry and academic researchers • create a researcher cohort with a state of the art skills pool, relevant to the European medical devices sector, for advanced industrial competitiveness and improved human potential • establish a long term S&T collaboration for continued ToK between the participant countries • isolate human scFvs that bind EPC markers with high affinity and specificity • covalently and directionally immobilise the scFvs on TiO2-based stent materials • demonstrate EPC coating of the stent disks in vitro • manufacture and evaluate a functionalised stent prototype for development, post-project, into a clinical product with significant economic and societal impacts. Description of scientific work performed in the project Recombinant antigens surfaced-exposed on endothelial or precursor endothelial cells were cloned and expressed in Escherichia coli. Purified proteins were used to isolate scFv antibody fragments that bind endothelial cells from a human antibody fragment library. After affinity ranking, lead scFvs were engineered to contain glycan- or cysteine-linkers for covalent, oriented attachment to stent surfaces. Titania-coated 316L stainless steel-based discs were functionalised with appropriate –SH or –NH groups for protein attachment and scFvs were immobilised, and the surfaces characterised. No cytotoxicity was observed and scFvs captured endothelial cells for improved surface coating. Sterilisation techniques were established for the biofunctionalised steel and commercial stents were produced and coated with the antibodies for improved cell capture and reduced thrombosis in vivo. Education and training Sixteen researchers received training in state-of-the-art techniques in protein engineering, materials science and medical devices production and analysis. Inter-sectoral secondments were complemented by formal training courses, networking events, and informal training of additional researchers through collaboration and a seminar series. The collaborative programme has developed individual researchers’ skill sets, strengthened research capacity at the partner institutions and supported important biomedical device clusters in Ireland, Poland and Slovakia. Materials and resources for public engagement and to increase public awareness of cardiovascular disease were also developed, including a flyer that was widely circulated by the Partners and a website (https://sites.google.com/site/mariecurieiappconsortium/home). Potential impact of the work The work has increased the human skills base in advanced materials and nanobiotechnology in Europe and contributed to the development of the European medical device industry. The longer term biomedical goal of the work is to realise a commercially viable, biocompatible and bioactive cardiovascular stent that will exhibit improved in vivo performance, leading to significant improvements in patient outcomes and a corresponding decrease in vital healthcare costs. For further information: Dr J. Gerard Wall Microbiology, NUI Galway, Ireland T: +353-91-495808; E: gerard.wall@nuigalway.ie Project website: https://sites.google.com/site/mariecurieiappconsortium/

Data: CORDIS, © European Union