Projects / Programmes source: ARIS

Modifications of surface of metallic biomaterials and their interaction with bio-environment

Research activity

Code Science Field Subfield
1.04.01  Natural sciences and mathematics  Chemistry  Phyisical chemistry 

Code Science Field
P401  Natural sciences and mathematics  Electrochemistry 

Code Science Field
1.04  Natural Sciences  Chemical sciences 
metallic biomaterials, simulated physiological environment, biological environment
Evaluation (rules)
source: COBISS
Researchers (19)
no. Code Name and surname Research area Role Period No. of publicationsNo. of publications
1.  11308  PhD Andrej Cör  Oncology  Researcher  2011 - 2014  403 
2.  28477  PhD Matjaž Finšgar  Chemistry  Researcher  2011 - 2012  385 
3.  04634  PhD Aleš Iglič  Systems and cybernetics  Researcher  2011 - 2014  945 
4.  14680  PhD Jernej Iskra  Chemistry  Researcher  2011 - 2014  395 
5.  33030  PhD Doron Kabaso  Physics  Researcher  2011 - 2012  26 
6.  27919  Barbara Kapun  Chemistry  Technical associate  2011 - 2014  76 
7.  23526  PhD Simon Kovač  Neurobiology  Researcher  2011 - 2014  174 
8.  31233  PhD Nataša Kovačević  Chemistry  Researcher  2013  45 
9.  08027  PhD Antonija Lesar  Chemistry  Researcher  2011 - 2014  121 
10.  24220  PhD Vesna Levašič  Neurobiology  Researcher  2011 - 2014  147 
11.  27526  PhD Maruša Lokar  Biochemistry and molecular biology  Researcher  2014  37 
12.  01290  PhD Ingrid Milošev  Chemistry  Head  2011 - 2014  686 
13.  29537  PhD Sebastijan Peljhan  Chemistry  Researcher  2012  57 
14.  32874  Mojca Seručnik  Biotechnology  Technical associate  2011  28 
15.  06058  PhD Stojan Stavber  Chemistry  Researcher  2011 - 2014  310 
16.  25786  Dunja Terčič  Biochemistry and molecular biology  Researcher  2011 - 2014  29 
17.  23524  PhD Rihard Trebše  Neurobiology  Researcher  2011 - 2014  408 
18.  34203  PhD Ekaterina Yurieva Gongadze  Neurobiology  Researcher  2011 - 2013  71 
19.  32927  PhD Gregor Žerjav  Chemical engineering  Junior researcher  2011 - 2014  188 
Organisations (3)
no. Code Research organisation City Registration number No. of publicationsNo. of publications
1.  0106  Jožef Stefan Institute  Ljubljana  5051606000  88,565 
2.  0355  Orthopaedic Hospital Valdoltra  Ankaran  5053765  2,306 
3.  1538  University of Ljubljana, Faculty of Electrical Engineering  Ljubljana  1626965  27,578 
Long-term performance of orthopaedic metallic implants is limited primarily by the process of aspetic loosening, it is endangered also by infection. The stability of an implant is based on a thin interface layer formed between metal surface and bio-environment. Its formation comprises a series of chemical, biological, biochemical and physical interacting processes. Implantation of metal implant in bio-environment has been mainly simulated in vitro through electrochemical corrosion measurements in solutions of anorganic salts. Such studies describe the behaviour of metallic biomaterials in simplified simulation of bio-environment and are important for the general knowledge on the materials and relative comparison among them. Such studies, however, cannot describe realistic physiological situation since they do not include biomolecules. The latter are interactively included in processes in vivo and should be taken into account to closely simulate physiological conditions. We have established that some selected compounds significantly affects the behaviour of metals in vitro. In the proposed project the following hypotheses will be integrally investigated: We will systematically study the effect of various glycozaminoglyans (GAGs) like hyaluronic acid and condroitin sulfate on the behavior of metallic materials in simulated physiological environment. These two compounds are commonly found in extracelullar matrix and are used for various applications from cosmetic surgery to cellular cultures. Their role in the events upon implantation of metals has been scarcely investigated despite some indicies that it may be important. We will additionaly test the effect of anorganic ions, mainly calcium and phosphorus. We hypothesize that these ions significantly affect the behaviour of particular metals in the presence of biomolecules like glycozaminoglycans. Furthermore, we will investigate the effect of proteins, mainly albumin, in the presence of GAG compounds and inorganic ions. Considering a wide spectrum of properties and processes regulated by these compounds we expect to gain important results on the mechanism of formation of metal/bio-environment interface. Interaction and event upon implantations are very important for the formation of stable implant/bone interface and can affect the long-term stability of the implant. Further, we will consider the possibility to modify the metal surface by GAGs and functionalize it for incorporation of antibacterial agents. Implant infection is a series complication, it requires a long-term antibiotic treatement. Often is the removal of the infected implant unavoidable. The efforts are therefore directed to research studies aimed to reduce the incidence of infection. The role of GAGs and proteins will be tested through test of incubation cell survival, proliferative activity and number of apoptotic cells. In collaboration with orthopaedic surgeons we will gain knowledge and data on samples of synovail fluid collected at surgeries. Proposed scientific hypotheses will be treated by different methods which will assure the integral methodological approach. For study of the corrosion stability, mechanism of electrochemical process and morphological, chemical, topographical and physical changes on the metal surface we will explore electrochemical and surface analytical methods. Methods of molecular dynamics and molecular mechanics will enable us to determine different helix conformations of GAGs and to identify the binding sites for inorganic ions (Na+, Ca2+). Based on the results of theory and simulation of electrostatic forces we will evaluate the role of electrostatic forces on the interaction between GAGs and metal surface. Cell culture experimentes will enable us to get the insight in the events on the cellular level.
Significance for science
Research results gained within the project contributed to the scientific community new important results. Interdisciplinarity of the project broadened the scientific methodology which could not be developed within individual scientific field – chemistry and medicine. Consequently, each of these two sciences gained and deepened the knowledge of its basic and applied research. Upgrade of classical in vitro studies contributed importantly to the knowledge on effect of biomolecules to the formation of surface layer under simulated physiological conditions. Proposed interdisciplinary approach thus enabled more qualitative treatment of the field of metallic implants and their impact in human body. The most important results gained within the project are as follows: - Based on the results of electrochemical measurements we gained quantitative and qualitative data on corrosion resistance of selected materials. We confirmed that hypothesis that GAGs affect the corrosion resistance of implant alloys in simulated physiological solution. - Surface analytical results enabled to gain an insight into the morphological, chemical, topographical and physical changes on the metal surface in the presence of GAGs in simulated physiological solutions. We confirmed the hypothesis that GAGs affect the formation and composition of the surface layer on particular metals. - Molecular dynamics methods enabled us to determine different helix conformations and to analyze which combination of H-bonds assures the most stable structure. Further, we identified the binding sites for inorganic ions. We confirmed the hypothesis that particular inorganic ions affect the conformation of the helix and, consequently, the flexibility of the compound. - Based on the results obtained in cell culture studies we confirmed that the surface film formed in the presence of GAGs affect the characteristic cell parameters. - In the presence of the GAGs the surface layer is formed which can be used as a matrix for improved functional performance of the metal implant. We could use this possiblity for targeted incorporation of various agents. We confirmed that such layers exhibit antibacterial activity. - Values of pH of synovial (joint) fluid differ at different iatrogenically induced conditions, e.g. optimally performing joint prosthesis and loosened joint prosthesis. Combining the experimental in vitro, theoretical and simulation methods and perioperative clinical measurements we gained many answers to most relevant issues concerning the stability of material under physiological conditions. These answers are of importance to the understanding of biomaterial interactions.
Significance for the country
Although the results of the proposed project do not have a direct impact for the economy, they contribute to the understanding of functioning metallic implants in vivo. In perspective this will contribute to their increased survivorship. Revision operations are not only unpleasant personal experience for the patient due to pain, limited range of motion and lastingness postoperative convalescence but also a financial burden to the health care funds and consequently to the society as a whole. With the scientific methodology and organizational approach we follow the trends in the scientific reseacrh, as evidenced by published scientific papers in leading orthopaedic journals and presentation at international conferences. This process certainly strenghten the position of Slovenia as an important country at the world scientific map. Scientific work leads to the close collaboration with international partners and access to thier knowledge, resulting in cooperation in common projects and publishing of common scientific papers. It is important that our work includes the education of young researchers. Last but not least the results of the proposed project are important primarily for the patients. Indirectly, however, this means that the results are important for the community as a whole since the improvement of the survirorship implies a decrease in the number of revision operations. Healthy individuals capable to perform their professional working tasks contribute to the general welfare of the community.
Most important scientific results Annual report 2012, 2013, final report, complete report on dLib.si
Most important socioeconomically and culturally relevant results Annual report 2012, 2013, final report, complete report on dLib.si
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