Projects / Programmes
Design, formulation and characterization of biomimetic nanocomposite systems for effective tissue regeneration
| 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 |
tissue regeneration, nanocomposites, electrospinning, biocompatibility, cell models
Researchers (27)
Organisations (6)
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
