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Projects / Programmes source: ARIS

Advanced hemocompatible surfaces of vascular stents

Research activity

Code Science Field Subfield
7.00.00  Interdisciplinary research     

Code Science Field
B530  Biomedical sciences  Cardiovascular system 

Code Science Field
3.02  Medical and Health Sciences  Clinical medicine 
Keywords
nanostructure, plasma treatment, stent, biocompatibility/hemocompatibility
Evaluation (rules)
source: COBISS
Researchers (19)
no. Code Name and surname Research area Role Period No. of publicationsNo. of publications
1.  01694  Zlatko Bele  Electronic components and technologies  Researcher  2016 - 2019  17 
2.  34541  PhD Metka Benčina  Materials science and technology  Beginner researcher  2016 - 2017  81 
3.  27558  PhD Silvo Hribernik  Textile and leather  Researcher  2016 - 2019  302 
4.  04634  PhD Aleš Iglič  Systems and cybernetics  Researcher  2016 - 2019  975 
5.  28480  PhD Ita Junkar  Medical sciences  Head  2016 - 2019  288 
6.  36303  PhD Rupert Kargl  Textile and leather  Researcher  2016 - 2019  292 
7.  37148  Judita Lea Krek  Neurobiology  Researcher  2016 - 2017  18 
8.  35435  PhD Mukta Kulkarni  Neurobiology  Researcher  2016  37 
9.  24332  PhD Manja Kurečič  Materials science and technology  Researcher  2016 - 2019  231 
10.  35503  PhD Tina Mavrič  Chemical engineering  Researcher  2017 - 2018  14 
11.  36461  PhD Luka Mesarec  Physics  Researcher  2017 - 2019  63 
12.  33768  PhD Tamilselvan Mohan  Textile and leather  Researcher  2016 - 2019  211 
13.  10429  PhD Miran Mozetič  Electronic components and technologies  Researcher  2016 - 2019  1,359 
14.  37482  PhD Matic Resnik  Electronic components and technologies  Junior researcher  2016 - 2018  52 
15.  07814  PhD Karin Stana Kleinschek  Textile and leather  Researcher  2016 - 2019  1,118 
16.  01718  PhD Iztok Šorli  Electronic components and technologies  Researcher  2016 - 2019  63 
17.  31673  PhD Roman Štukelj  Sport  Researcher  2017  119 
18.  20048  PhD Alenka Vesel  Electronic components and technologies  Researcher  2019  697 
19.  34203  PhD Ekaterina Yurieva Gongadze  Neurobiology  Researcher  2016 - 2019  73 
Organisations (4)
no. Code Research organisation City Registration number No. of publicationsNo. of publications
1.  0106  Jožef Stefan Institute  Ljubljana  5051606000  91,921 
2.  0341  MIKROIKS, microelectronics engineering, consulting and service  Ljubljana  5286646  70 
3.  0795  University ob Maribor, Faculty of mechanical engineering  Maribor  5089638010  24,090 
4.  1538  University of Ljubljana, Faculty of Electrical Engineering  Ljubljana  1626965  28,004 
Abstract
The project will focus on improving surface properties of stents made of titanium. Although titanium alloys are extensively used for stent application they still lack of desired biological response, mostly due to restenosis. Restenosis presents a huge problem on all stent surfaces. It occurs in more than 33% of the cases, with higher possibilities in patients with high risk factors, such as diabetes. The stents can be divided in bare metal stents (BMS) and drug-eluting stents (DES). With DES the problems of allergenic reactions as well as risks of restenosis were lowered, as DES release anti cell-proliferative, immunosuppressive or anti-thrombogenic drugs which inhibit proliferation of smooth muscle cells and reduces thrombus formation. However it was shown that DES also inhibits normal endothelium growth which potentially leads to thrombosis. The probability of death by cardiac infarction in the period of 6 months to 3 years after implementation of DES was 32% higher than on BMS [Lagerqvist B. et al., New England Journal of Medicine 2007, 356, 1009-1019]. Therefore in the last few years adverse clinical data linking DES usage to arterial thrombosis had led to a large decrease in sales. Furthermore, companies are seeking to develop novel stents, while so far the improvements on DES are merely incremental. Innovations are done mostly on the polymer coatings, stent platforms and on drug components. Moreover DES are almost three times more expensive compared to BMS. Therefore the main goal of the proposed project is to provide advanced stent surfaces which will lower the risk of restenosis as well as thrombosis, without the need to use coatings. This will be achieved by electrochemical anodization and plasma treatment technique. By electrochemical anodization we will form self-assembled layers of vertically oriented TiO2 nanotubes with defined diameters between 15 and 100 nm. These surfaces will be further treated by highly reactive plasma in order to increase oxygen content on the surface and to remove surface residues obtained from electrochemical anodization. As sterilization is the final surface treatment step, which should be considered before implementation, systematic studies on effects of commons sterilization techniques on surface properties as well as on the biological response will be conducted. Biomimetic surfaces are increasingly recognized for their surface features as they were shown to highly influence on tissue acceptance and cell survival. However effects of surface chemistry and wettability should not be neglected as synergistic effects can be achieved by fine tuning morphological and chemical features. Our previous results (obtained in the frame of ARRS project »Preparation of hemocompatible polymeric surfaces for biomedical applications«, Z3-4261, 2011 to 2013) on plasma treatment of vascular grafts made of polymers indeed showed significant reduction in platelet adhesion and activation, while enhanced proliferation of endothelial cells due to nanostructuring and functionalizing the surface by plasma (formation of oxygen functional groups). As titanium surface cannot be nanostructured by plasma, electrochemical anodization will be employed and surface chemistry will be appropriately altered by high reactive plasma. In tight collaboration with experts in material engineering, surface sciences, plasma physics and medicine we will be able to accomplish desired biological response on titanium surface. Therefore we aim to develop new generation stents by combining the two novel techniques (electrochemical anodization and plasma treatment). By this we believe to fabricate appropriate nanostructure as well as surface chemistry which will reduce smooth muscle cell growth, prevent platelet adhesion while promoting proliferation of endothelial cells.
Significance for science
The results of the project will provide new highly valuable knowledge on interaction phenomena of nanostructured surfaces with whole blood (adhesion and activation of platelets), selectivity of nanostructured surface on interaction with various cell types (fibroblast cells, endothelial cells, smooth muscle cells) and two important blood plasma proteins (fibrinogen and albumin). These effects of nanotopography on interaction with whole blood are still not well understood. Presently the designing of blood compatible devices is highly challenging as no exact information about which surface parameters actually play a predominant role in platelet adhesion and activation. With the development of nanotechnologies we are now able to produce biomimetic surfaces, which mimics natural nanostructure of tissue and could provide appropriate biological response. For further development of optimal blood compatible devices it is crucial to study the effects of different surface nanotopographies on blood compatibility. The gained knowledge may become a milestone in production of the new generation of high value added biomimetic stent surfaces which will highly reduce stent connected complications. This may lead to the development of novel stent devices in medicine which will reduce post-surgical complication and lower the risks of thrombosis. During project duration we will not only gain new insights on interaction mechanisms of cells with TiO2 nanostructured surfaces, but also on the effects of surface morphology, chemistry and wettability on in vitro biological response.  Moreover, the proposed work will be highly interdisciplinary and transdisciplinary as people from different fields (physic, chemistry, microbiology, mechanical engineering etc.) will work in tight collaboration and will together create superior knowledge which could be used in different fields of work.
Significance for the country
The biomedical market is known to be one of the biggest and most rapidly growing markets and is recognized for its high value added products. In the last years companies are investing a lot of money in the research and development of new materials for medical applications, as this presents their advantage over the competitors. The research done on surfaces used for medical devices in Slovenia is mainly carried out by various research organizations while there are not many companies dealing with development of new medical devices. The main reasons lie in the lack of nanotechnology expert knowledge in the field, lack of transdisciplinary expert knowledge, high research expenses (scientists, costly research equipment), and the time consuming research period before the product may reach the market and make profit. The results of this proposed project will bridge the main drawbacks with which most of the companies dealing with medical devices development are facing. The new knowledge on cell-biomaterial interactions will enable companies to produce high tech and high value added products, which will improve quality and longevity of people’s lives. Moreover, the companies will be able to expand their product range, increase profits, increase competitiveness and create new high quality working places. The development of new knowledge will also promote development of biomaterial scientific field and will improve education capabilities.
Most important scientific results Interim report, final report
Most important socioeconomically and culturally relevant results Interim report, final report
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