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.