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Projects / Programmes source: ARIS

Design, formulation and characterization of biomimetic nanocomposite systems for effective tissue regeneration

Research activity

Code Science Field Subfield
1.09.00  Natural sciences and mathematics  Pharmacy   

Code Science Field
B740  Biomedical sciences  Pharmacological sciences, pharmacognosy, pharmacy, toxicology 

Code Science Field
3.01  Medical and Health Sciences  Basic medicine 
Keywords
tissue regeneration, nanocomposites, electrospinning, biocompatibility, cell models
Evaluation (rules)
source: COBISS
Researchers (27)
no. Code Name and surname Research area Role Period No. of publicationsNo. of publications
1.  15104  PhD Saša Baumgartner  Pharmacy  Researcher  2011 - 2014  306 
2.  04657  PhD Marija Bešter Rogač  Chemistry  Researcher  2011 - 2014  458 
3.  32694  PhD Katarina Bolko Seljak  Pharmacy  Researcher  2011 - 2014  55 
4.  22603  PhD Jožica Dolenc  Chemistry  Researcher  2011 - 2013  52 
5.  11789  PhD Mirjana Gašperlin  Pharmacy  Researcher  2011 - 2014  600 
6.  28446  PhD Ilija German Ilić  Pharmacy  Researcher  2011  143 
7.  29887  PhD Mirjam Gosenca Matjaž  Pharmacy  Researcher  2011 - 2013  142 
8.  17433  Tatjana Hrovatič    Technical associate  2011 
9.  34670  PhD Biljana Janković  Pharmacy  Researcher  2012  137 
10.  01302  PhD Matjaž Jeras  Biotechnology  Researcher  2011 - 2014  364 
11.  18699  Mojca Keržan    Technical associate  2011 - 2014 
12.  24402  PhD Petra Kocbek  Pharmacy  Researcher  2011 - 2014  296 
13.  09032  PhD Julijana Kristl  Pharmacy  Head  2011 - 2014  932 
14.  14574  PhD Mojca Urška Mikac  Physics  Researcher  2011 - 2014  151 
15.  30807  PhD Mihael Munda  Oncology  Researcher  2012 - 2014  54 
16.  03070  PhD Slavko Pečar  Pharmacy  Researcher  2011 - 2014  415 
17.  33909  PhD Jan Pelipenko  Pharmacy  Junior researcher  2011 - 2014  44 
18.  07625  PhD Milan Petelin  Stomatology  Researcher  2011 - 2014  243 
19.  14935  PhD Odon Planinšek  Pharmacy  Researcher  2011 - 2014  440 
20.  32039  PhD Romana Rošic Danko  Pharmacy  Researcher  2011 - 2013  43 
21.  07925  Ana Sepe    Technical associate  2011 - 2014  131 
22.  09031  PhD Stanko Srčič  Pharmacy  Researcher  2011  675 
23.  30336  PhD Bojan Šarac  Chemistry  Researcher  2012 - 2014  104 
24.  29888  PhD Rok Šibanc  Pharmacy  Researcher  2013 - 2014  63 
25.  07798  PhD Draga Štiblar Martinčič  Oncology  Researcher  2011 - 2014  161 
26.  26198  PhD Urban Švajger  Microbiology and immunology  Researcher  2012 - 2014  204 
27.  26226  PhD Alenka Zvonar Pobirk  Pharmacy  Researcher  2011 - 2013  212 
Organisations (6)
no. Code Research organisation City Registration number No. of publicationsNo. of publications
1.  0103  University of Ljubljana, Faculty of Chemistry and Chemical Technology  Ljubljana  1626990  23,187 
2.  0106  Jožef Stefan Institute  Ljubljana  5051606000  90,976 
3.  0311  Blood Transfusion Centre of Slovenia  Ljubljana  5053960  1,737 
4.  0312  University Medical Centre Ljubljana  Ljubljana  5057272000  77,744 
5.  0787  University of Ljubljana, Faculty of Pharmacy  Ljubljana  1626973  17,246 
6.  2334  University of Maribor, Faculty of Medicine  Maribor  5089638048  16,591 
Abstract
The project is based on the demand for transfer of the fundamental knowledge into the development of modern products for tissue regeneration to improve the quality of patient’s life and reduce the treatment expenses. The novelty of the project is systematic approach to the formulation of nanocomposites focused on nanofibers produced by electrospinning as an up-to-date method. The additional innovation is evaluation of regeneration using organotypic skin substitutes. New strategies for effective healing will be applied by incorporation of cells as a source of cytokines into biomimetic nanocomposites.   The innovation chain of the project includes the following elements   Concept:  polymer selection › selection of suitable technology › characterization of polymer dispersions › optimization of technological procedure › design and development of nanofibers (plain or with drug) › verification › feed-back optimization › biological testing.   Scientific background and problem identification Chronic diseases of the modern world are often linked to tissue damage and demands specific treatment. For efficient regeneration it is essential to reestablish normal balance of factors involved in healing process with the use of the system close to the size of the cells. According to up-to-date studies nanocomposites represent promising therapeutic devices. The lack of systematic studies providing the complete image of nanocomposite preparation has directed our project to predict processibility from starting material to the final product. The aim of the research is to contribute to the understanding of the relationship between the properties of polymer solutions and to exploit them in the formulation of the final product. To understand the biocompatibility of nanocomposites and to evaluate their efficacy in the regeneration biological studies will be performed. By knowing all these characteristics and their interplay the design of safe and efficient nanocomposites for tissue regeneration will be improved. The aims of the research are the following: 1. Fundamental preformulation studies: from material selection to nanocomposites The most suitable biocompatible materials will be chosen, their physical characteristics per se and in dispersions will be evaluated and correlated with further technology based on polymer molecular structure. The selection of drugs relevant for regeneration will be based on recently published scientific findings. Additionally, method for isolation of leukocytes and macrophages as a source of growth factors will be developed. 2. Formulation, physico-chemical and technological evaluation of nanocomposites Preparation of nanocomposites has to be reproducible; therefore the influence of technological production parameters on the processibility should be investigated. From the already known parameters the key factors that enable stable production should be selected. Precisely as nanocomposites, electrospun nanofibers will be developed. The drug alone or in nanoparticles will be incorporated in nanofibers. Further, nanofibers or nanoparticles will be incorporated in hydrogels and compared with simple hydrogels. 3. Biological evaluation of nanocomposites To achieve the presented aims the fundamental biological evaluation of prepared nanosystems will be carried out and in the final stage of the research the proof of concept will be performed using organotypic skin substitutes.   Relevance of the proposed research The project will be carried out by an interdisciplinary team to assure high scientific relevance, effective exchange of knowledge and access to the necessary infrastructure. The vision of the proposed study is not only to gain some new fundamental knowledge and skills, but above all applicability of formulated nanocoposites. Our research follows the latest scientific findings in the areas of materials, formulation technologies and tissue regeneration and thus creates new research goals in this interdisciplinary fi
Significance for science
The current doctrine of treatment and a number of internationally renowned publication show that available therapeutic approaches do not provide optimal conditions for tissue repair. On the other hand, nanocomposite systems represent a huge challenge in different scientific fields, each of them having a specific view on the characteristics and advantages of nanomaterials. The approach used in the project tried to link knowledge from the different disciplines and targeted it towards understanding of nanocomposites and their role in the process of tissue regeneration. The project was based on the principle of the model of increased complexity, which means from the knowledge and research of source materials, through preformulation and formulation studies, towards the end product and its biological evaluation. The polymer nanofibres were shown to be a promising material for effective treatment and regeneration of tissues according to the current findings. Systematic investigation has enabled selection of biocompatible polymers, correlation of their characteristics with processibility and properties of the produced nanocomposite. Such correlation has not been known previously; therefore, our study sets the guidelines for future development of nanofibres for effective tissue regeneration. Despite the knowledge about the impact of different parameters on electrospinning process its prediction based on evaluation of individual physical parameter of polymer solutions, control over process variables and environment conditions is very difficult. The parameters that have the greatest predictive power were shown to be interfacial viscosity of polymer solution and radius of gyration. Furthermore, the relative humidity of the environment in which electrospinning is performed, was shown to be a critical parameter of the environment, which has not been studied systematically in previous studies. Thus, the understanding of the electrospinning process as well as prediction of its feasibility has been improved. The bioevaluation using skin cell cultures revealed that the cell response on nanofibers depends on the cell type and properties of nanofibres. Low molecular weight drugs as well as biomacromolecules can be incorporated in nanofibers by electrospinning. Incorporation of growth factors in form of platelet rich plasma revealed that electrospinning does not adversely affect their bioactivity. The synergistic effect of nanotopography and incorporated growth factors on the proliferation of skin cells in vitro has been confirmed, suggesting the reasonableness to plan further preclinical and clinical research on nanofiber application in tissue regeneration in vivo.
Significance for the country
The pharmaceutical industry has a great socio-economic impact in every country. It produces high quality, safe and effective medicines and medicinal devices and with them competes on the domestic and the global market. Our studies were directed towards competitiveness of the Slovenia’s economy as well. New knowledge gained in the project can be implemented in the development of nanocomposites for the tissue regeneration and wider, enabling faster development of modern medical devices and medicines. Systematic investigation of a range of biocompatible polymers and their properties correlated with their processibility and characteristics of nanocomposites enabled setting up a platform, which will enable a fast transition from lab to industrial scale. The measurements of interfacial rheology, relative humidity and mechanical properties of nanofibres have revealed important aspects, which can reduce the risk in development of novel nanomedicines based on nanofibres. New knowledge and experiences, gained in the project, enable further development towards marketable products and protection of intellectual property. Project was a great opportunity for young perspective undergraduate and postgraduate students, which have learned about electrospinning and analytical methods (2 finished PhD studies, 17 finished diploma and master thesis). With research work and processing as well as interpretation of obtained results they gained the necessary experience and laboratory skills and developed the ability of critical thinking. The project has provided environment for creative and innovative interdisciplinary work of the young staff. Our project has contributed to pursuing one of the fundamental objectives of Slovenia's development strategy - that is the direct transfer of knowledge from academia to industry, since J. Pelipenko has employed in the pharmaceutical industry after he finished his PhD study (Lek d.d.). On the other hand, the project results represent the potential for improving the quality of life of patients, whose pathology is associated with tissue damage and thus its treatment requires adequate regeneration. The number of such patients is increasing due to aging population and unhealthy life style (e.g. obesity, diabetes, cardiovascular disease), thereby increasing the need for new and more effective materials for tissue regeneration. Polymer nanofibres have shown a great potential for active tissue regeneration in the performed in vitro study. Further research will facilitate their transition into clinical testing and build the strategies for more effective treatment and c The achievements of the research project have been presented in various manners to the domestic and international scientific community, namely in the form of 24 scientific contributions at conferences and 12 papers published in well-known international journals, thus promoting Slovenia and Slovenian science.
Most important scientific results Annual report 2011, 2012, 2013, final report, complete report on dLib.si
Most important socioeconomically and culturally relevant results Annual report 2011, 2012, 2013, final report, complete report on dLib.si
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