| Biography | |
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 Prof. Miran Mozetič Jozef Stefan Institute, Slovenia |
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| Title: Application of Microwave Technologies to Improve Biocompatibility of Cardiovascular Implants | |
| Abstract:
Cardiovascular diseases nowadays represent the major cause of death and the costs of curing such diseases have exceeded 1,000 B€ annually years ago. The atherosclerosis, the major precursor of such diseases, is often associated to clinical complicationsthat can occur in different vascular regions, such as coronary heart disease, carotid artery disease,peripheral artery disease, and atherosclerotic renovascular disease. Major risk factors for developing cardiovascular diseases encompass smoking, diabetes, physical inactivity,unhealthy diet, cholesterol, obesity, increasing age, autoimmune diseases,hypertension, infections, gender, and a family history of vascular disease. Apart from avoiding risk factors there are little effective substances that are capable of suppressing the symptoms; instead, a variety of cardiovascular implants have been used in clinical praxis for decades. Most frequent ones are vascular stents - scaffolding devices used to holdtissue in place in a specific stretched or taut position. Badly damaged blood vessels are replaced with artificial ones (vascular grafts) or bypassed with a blood vessel graft in order to restore normal bloodflow. The purpose of bypass grafting is to supply blood to distal circulationbeyond the significant stenosis, using a graft which is made of biologicalmaterials (usually patients’ own venous or arterial conduits) or syntheticmaterials. Wherever possible, replacement of the diseased blood vessel by anautograft is the best choice. Unfortunately, patients with preexisting vasculardiseases usually do not have healthy enough blood vessels that could adequatelyreplace the diseased parts.
Any synthetic material lacks biocompatibility. Vascular stents are often made from metallic mesh while artificial blood vessels are usually made from polymers. These materials are found foreign by patients so post-surgery complications are common. The risk of thrombosis is high so a patient should take large doses of anti-coagulant pills for months or years, frequently for the rest of his/her life. The major side effect is a result of a simple fact that anti-coagulants prevent blood coagulation also when it is necessary. Even small bleeding is regarded serious and could be fatal in extreme cases. Obviously, a key breakthrough in this segment of medicine would be avoiding the anti-coagulant drugs as well as reducing health care costs due to post-surgical complications. This is not possible to achieve with currently available vascular grafts, since blood platelets recognize the graft as a foreign material, adhere on the surface, change the morphology, release enzymes and factors that cause transformation of blood proteins, formation of fibrin network, capturing blood cells and ultimately formation of a thrombus.
A suitable method for improving of vascular grafts biocompatibility is either nano-structuring of original smooth polymeric grafts of application of various coatings. In both cases one can apply non-equilibrium gaseous technologies for tailoring the properties of inner surfaces. Typically, a non-equilibrium state of gas is obtained in gaseous plasma. Such a plasma can be created by various electrical discharges but is difficult if not impossible to assure for uniform treatment of long cylindrical objects of typical length several cm or even more than 10 cm and diameter few mm. A feasible solution is application of microwave technology.
Highly non-equilibrium gaseous medium was sustained inside a polymeric vascular graft using microwave-driven gaseous discharge. A microwave generator operating at the standard frequency of 2.45 GHz was connected to a metallic cavity. Inside the cavity we placed a quartz tube of diameter 5 mm. Commercially available oxygen of purity 99.99% was introduced into the quartz tube. Upon application of high electromagnetic field gaseous plasma was formed inside the tube. The high frequency of the electromagnetic field prevented propagation inside the electrically conductive plasma so the waves rather propagated within the sheath between electrically conductive plasma and the surface of the quartz tube. A polymeric vascular graft of diameter 6 mm was mounted on the quartz tube and was movable so that non-equilibrium gas at the exhaust from the quartz tube interacted with the inner surface of the graft along the entire graft length which was 15 cm. The quartz tube and the vascular graft were placed into a vacuum chamber which was continuously pumped with a two-stage rotary pump. The gas drift allowed for a high density of reactive oxygen species (ROS) inside the vascular graft. The species interacted readily with the inner wall of the polymeric graft causing two effects: i) functionalization with polar functional groups, and ii) increase roughness of the polymeric fibres (the graft was knitted) on the sub-micrometer scale. Both effects resulted in the super-hydrophilic surface finish. The type of functional groups was determined by X-ray photoelectron spectroscopy (XPS), the roughness by atomic force microscopy (AFM) and the wettability by water contact angle (WCA). The super-hydrophilic surface finish was obtained after about 6 minutes of treatment. XPS showed increased concentration of highly polar carboxyl and hydroxyl groups while AFM rich morphology at average roughness Ra of 6 nm on the 1 µm x 1µm surface area. The WCA was immeasurably low since water droplet wetted the graft immediately. Such a surface finish enabled appropriate conformation of blood constituents on the inner surface of the vascular graft upon incubating with human blood. The super-hydrophilic surface finish probably facilitated formation of a thin water film on the polymer surface thus preventing transformation of fibrinogen to fibrin fibres. The concentration of blood platelets in activated state on the surface of the vascular graft dropped for over 100 times as compared to results obtained for untreated grafts. Improved biocompatibility was observed already at the ROS fluence of about 1024 m-3 but best results were obtained at the fluence of about 2.5x1025 m-3.
Keywords: GHz, plasma, vascular grafts, biocompatibility
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| Biography:
Prof. Dr. Miran Mozetič received his B. Sc. Degree of Physics from the Faculty of Natural Sciences and Technology, University of Ljubljana, Slovenia in 1988. In 1992 he received the M. Sc. Degree from the Technical Faculty, University of Maribor, Slovenia, and in 1997 the Ph. D. Degree of Electronic Vacuum Technology from the Faculty of Electro-technique, Computer Sciences and Informatics, University of Maribor. In 1993 he attended courses on Application of synchrotron radiation techniques at International centre for theoretical physics in Trieste, Italy. He joined Jožef Stefan Institute in 2003 and since 2009 he is the Head of Department F4 (Department of Surface Engineering). He is the leader of a research group (currently 20 members + several students) working on application of radio-frequency and microwave sources for generation of highly reactive gaseous plasma as well as applications of high-frequency gaseous discharges in automotive industry, nanotechnology, agriculture and medicine. He has been a partner in numerous national and over 10 EU projects. He is a full professor at University of Ljubljana and International postgraduate school Ljubljana.He served as a guest lecturer at University of Ioannina, Greece, Universite Paul Sabatier, Toulouse, France, University of Leeds, England, University of Louisville, Kentucky, U.S.A., University of Nagoya, Japan, Universite du Maine, Le Mans, France, University of Sydney, Australia, Nanyang University of Technology, Singapore, Kyushu University, Fukuoka, Japan, University of Illinois, Urbana, USA, University Tomas Bata, Zlin, Czech Republic and Mahatma Ghandi University, Kottayam, India. His bibliography includes over 250 scientific papers and 20 patents. His papers have been cited over 4000 times and his Hirsch index is 36. He is a member of scientific or organizing committees of different conferences and workshops, a member of different scientific and professional societies, and a reviewer of papers submitted to numerous SCI journals. Between 2007 and 2013 he was the President of Slovenian vacuum society and since 2010 he is the chair of Education Committee of International Union for Vacuum Science, Technology and Applications – IUVSTA. In 2011 he received the most prestigious Slovenian prize for technology transfer to industrial production – “Puh award”.
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