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Projects / Programmes source: ARIS

Bioactive materials with immobilized bifunctional peptides for biomedical applications

Research activity

Code Science Field Subfield
2.04.03  Engineering sciences and technologies  Materials science and technology  Polymer materials 

Code Science Field
P360  Natural sciences and mathematics  Inorganic chemistry 
T390  Technological sciences  Polymer technology, biopolymers 
T490  Technological sciences  Biotechnology 
B510  Biomedical sciences  Infections 
Keywords
biomaterials, peptides, immobilization, antimicrobial, endotoxin neutralization, bacterial biofilm
Evaluation (rules)
source: COBISS
Researchers (6)
no. Code Name and surname Research area Role Period No. of publicationsNo. of publications
1.  07731  PhD Jožefa Friedrich  Biotechnology  Head  2007 - 2009  184 
2.  06628  PhD Roman Jerala  Biochemistry and molecular biology  Researcher  2007 - 2009  1,203 
3.  27945  PhD Ivan Jerman  Chemistry  Researcher  2007 - 2008  389 
4.  21426  PhD Mateja Manček Keber  Pharmacy  Researcher  2008 - 2009  159 
5.  02565  PhD Boris Orel  Chemistry  Researcher  2007 - 2008  981 
6.  17280  Darija Oven    Technical associate  2007 - 2009 
Organisations (1)
no. Code Research organisation City Registration number No. of publicationsNo. of publications
1.  0104  National Institute of Chemistry  Ljubljana  5051592000  21,261 
Abstract
 Bacterial infections represent one of the most serious risks for human health. A special threat are bacterial biofilms, surface grown bacterial communities, which are outmost resistant to antibiotics. They represent one of the biggest problems for biomedical devices, such as catheters and implants. Some problems of device-related infections caused by biofilm formation are trying to be solved by the application of materials, which release antimicrobial substances. However, by liberation into the environment such substances gradually loose their efficiency and antimicrobial activity alone is not sufficient any more. Namely, a bacterial endotoxin released from the destroyed bacterial cells can cause inflammation and even sepsis. Therefore, it is desired to develop new materials, which would have in addition to antimicrobial activity also the ability to neutralize endotoxin. In the present project we propose creation of materials with conjugated bifunctional peptides possessing antimicrobial activity along with the ability to neutralize bacterial endotoxin. It is expected that after immobilization the peptides will have improved antimicrobial activity compared to free peptides. Due to high surface density of the immobilized peptides these are able of more efficient action on a bacterial membrane through the so called »carpet model«. Another advantage of the proposed approach is in the possibility to use peptides that are toxic in free circulation. Such example is a cyclic lipopeptide polymixin B, which is one of the best endotoxin neutralizers. This peptide, as well as other peptides with a wide spectrum of activities that were prepared in the frame of the EU project ANEPID, will be immobilized on the surface of different polymeric materials usually used in medicine, such as polysiloxanes (silicones), polyvinylchloride, polyuretanes etc. and also on the surfaces of materials made by sol-gel technology. We intend to measure several characteristics of the bioactive materials, among them spectrum of antimicrobial activities, binding capacity of endotoxin, stability, sensibility to ionic strength, possibility of material regeneration and determine the mechanism of activity on bacteria. In the case of promising results we will make a prototype of a catheter and test it in vitro and in vivo. In addition to the protective action the materials will also be tested for medical and pharmaceutical applications, e.g. for endotoxin elimination and also for biotechnological applications.
Significance for science
Microbial biofilms are populations of microoganisms that are attached to the surface of solid materials. Bacteria growing in a biofilm differ markedly from their planctonic counterparts : in expression of genes, cell physiology and in their increased resistance to antibiotics. Therefore, biofilms represent a severe problem in medicine and the best approach to solve the problem is to prevent biofilm formation. In our project we showed a possibility of using a novel original approach. We show that it is possible to create materials with antimicrobial activity on the surface by covalent binding of bioactive peptides via a suitable silane coating. By proper selection of peptides, in addition to antimicrobial activity, such surfaces can bind bacterial endotoxins, known to have dramatic clinical consequences when present in blood. Such surface coatings can be suitable for application on medical devices, such as different implants, to prevent bacterial biofilm formation. Research in the field of development of novel biomaterials for medicine one one hand and of antimicrobial peptides on the other hand is of great scientific interest what enables publication in recognized international scientific journals. In future, the obtained new knowledge can lead to economic exploitation.
Significance for the country
We present a new approach to solve the problem of bacterial biofilm formation on medical devices, such as different implants. The research is interdisciplinary, connecting knowledge of different area, such as nanomaterilas, biotechnology, biochemistry, microbiology and medicine. It resulted in acquiring new knowledge and development of novel, complex methodologies, and testing of applicability of modern analytical techniques for the concrete problem. A new possibility of development of original technologies and novel products is presented. All these can contribute to the technological and economic development of Slovenia. Finally, the application of the novel products is intended to improve health care. Results of our research are published in the international scientific literature and are presented to broader audience at the national and international scientific meetings. Together with our collaborators in a previous EU project we have prepared an international patent application. All mentioned activities contribute to promotion of Slovenia in the World. Within the project, supervision of young researchers was included. They successfully finished PhD theses and acquired new knowledge and experiences in the filed of designing and production of novel biomaterials, development and use of demanding analytical, microbiological and biochemical methods. All these contributed to education and formation of a versatile scientific staff.
Most important scientific results Annual report 2008, final report, complete report on dLib.si
Most important socioeconomically and culturally relevant results Annual report 2008, final report, complete report on dLib.si
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