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Dual Function Polymer Materials for Blood Contacting Applications

Periodic Reporting for period 1 - DualFun (Dual Function Polymer Materials for Blood Contacting Applications)

Reporting period: 2017-09-18 to 2019-09-17

Biomedical devices are a vital option of lifesaving therapy to thousands of patients every day. Surface-induced thrombosis and infection are two main complications which cause failure of medical devices. Infection is another significant problem, with 1.7 million Healthcare Associated Infections that result in 99,000 deaths per year in the United States alone. Therefore, the aim of the project was to produce polymer materials with dual function: thromboresistant and antimicrobial. Cu and Se catalyst species were attached to polyvinyl chloride (PVC) and polyurethane (PU) for nitric oxide (NO) generation by decomposition of endogenous S-nitrosothiols (RSNOs) as NO prevents bacterial film formation, to inhibit platelet adhesion/activation. Argatroban (AG), a direct thrombin inhibitor, was chemically immobilized on the surface of polymers in order to inhibit any surface-produced thrombin. Cu/AG- and Se/AG-modified PVC and PU were characterized by physico-chemical methods. Cu/AG- and Se/AG-modified polymers showed NO generation ability in PBS and in human plasma. Cu/AG- and Se/AG-modified PU and PVC effectively inhibited thrombin activityin buffer system and in platelet poor plasma or platelet rich plasma, thus preventing the platelet activation and aggregation. Another important achievement is that modified polymers showed antibacterial effect.
The project results will help to open wide opportunities for the improvement of the existing blood-contacting devices and design of new ones. The understanding of NO generation mechanism and argatroban activity may lead to the construction of the better quality blood compatible surfaces with more controllable properties. The applications for these materials range from the medical device technologies to the drug delivery systems in cardiovascular stenting, creation of biosensors for diagnostics and a smart textile design. The continuation of work can result in development of thromboresistant coatings on different polymers.
Collaborative work with Teer Coatings resulted in development of smooth metal/mixed metal coatings on synthetic polymers. These coatings are the highest quality reagent-fee coatings for polymers which is “green way” alternative technology to produce such coatings with significant reduction in waste generation. All obtained Cu-coated polymers were able to generate nitric oxide.
The project helped Dr Azizova to broaden her knowledge in the area of the surface chemistry of the implanted devices, antimicrobial activity, hemocompatiblity, thromboresistance, blood clotting, cell-biomaterial interactions. The University of Brighton provided Dr Azizova with opportunities to supervision/co-supervision of 5 student projects in pharmacy, biomedical science and biomaterials. The training obtained during MSCA fellowship has supported her professional development, strengthens her knowledge in project management, has helped her to widen scientific connections and network with researchers across the world.
PVC and PU polymers modified with Cu and Se for catalytic nitric oxide (NO) generation were produced. Further, thrombin direct inhibitor Argatroban was chemically attached onto the Cu/Se-modified polymers surface. Modified polymers were characterized using FTIR, ICP-OES, ICP-MS, XPS. The concentration of argatroban immobilized on polymers was found. The NO generation ability of polymers in both PBS and human plasma were tested and showed that modified polymers are capable of providing the physiological level of NO at physiological pH. The obtained data suggest that obtained polymers potentially can produce NO in the blood from endogenous S-nitrosothiols. The obtained data suggest that argatroban Cu/Se-modified polymers potentially can produce nitric oxide in the blood from endogenous RSNOs. Additionally, argatroban Cu/Se-modified PVC and PU effectively inhibited thrombin activity in a buffer system and in platelet-poor plasma or platelet-rich plasma, thus preventing the platelet activation and aggregation. Antibacterial ability of polymers was assessed on S. aureus and E. coli. Argatroban Cu/Se-modified polymers showed antibacterial effect during 2h of incubation with S. aureus and E. coli under conditions close to physiological.
The project results were presented at 3 international conferences and in 1 UK-based conference: 4th International Conference on Biomedical Polymers & Polymeric Biomaterials (Krakow, Poland); 16th Polish-Ukrainian Symposium Theoretical and Experimental Studies of Interfacial Phenomena and Their Technological Applications (Lublin, Poland); 29th Annual Meeting of the European Society for Biomaterials (Maastricht, The Netherlands); 4th Annual Conference and Expo on Biomaterials (London, UK). My presentations drew attention of researchers around the world and the representatives of medical device manufacturers, in particular, Arburg company, one of the leading global manufacturers of plastic processing machines.
Moreover, the project aims and results were discussed in 2 meetings in Teer Coatings and Pharmidex. It was productive meeting with rewarding discussions. Our colleagues from industry expressed a great interest to continue communication with the aim to write collaborative projects.
Also, students were involved in research work for testing NO generation abilities of modified polymers. Research work on project was very rewarding for students and encouraged research project student Lydia Smith to apply for a PhD programme at the University of Nottingham.
The project aims and results were presented in 2 University seminars organized by the host group. A project webpage was created on university website and recently updated. A short project video with project aims and outcomes was created and advertised in social media. These will help to increase visibility of project.
The Fellowship gave the applicant experience and knowledge that will help her to lead and guide an interdisciplinary biomaterials group and department with Ukrainian scientists at her home country. This is relevant especially because of new rules when group of young scientist can be led by young scientist with 2 years’ research experience in European university and in the light of the strategy of Ukraine's ambition to join the European Union. Her home institute, Institute of Surface Chemistry, supports her professional development, and achievement of coherent and impactful scientific discoveries according to the highest European and international standards. The fellowship enabled her to proceed with fundamental and applied research involving international research networks with academic and industrial partners. All of this has helped the fellow and her home institution become more competitive by participating in joint EU proposals for funding with other European research teams. Also, both research communities in Ukraine and UoB benefit from Dr Azizova’s international links, which can combine the collective expertise and create synergy in order to solve various problems in the field of medical devices.
The project results have a profound impact on fellow’s research in biomaterials area and benefit the European research community and society through the generation of new knowledge and innovation.
Moreover, the fellowship helps towards retraining women scientists and recommencing a scientific research career after career breaks such as parental leave in the same way promoting the role of women in science.
meeting in Teer Coatings ltd
platelet aggregation by Cu/AG-modified polymers
Secondment in Teer Coatings
antibacterial activity of Cu/AG-modified polymers