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Projects / Programmes source: ARIS

Emulsion templating of three-dimensional synthetic polypeptide-based macroporous scaffolds

Research activity

Code Science Field Subfield
2.04.00  Engineering sciences and technologies  Materials science and technology   

Code Science Field
T390  Technological sciences  Polymer technology, biopolymers 

Code Science Field
2.05  Engineering and Technology  Materials engineering 
Keywords
Synthetic polypeptides, ring opening polymerization, scaffolds, high internal phase emulsions, cell culture
Evaluation (rules)
source: COBISS
Researchers (11)
no. Code Name and surname Research area Role Period No. of publicationsNo. of publications
1.  18325  PhD Simon Caserman  Biochemistry and molecular biology  Researcher  2018 - 2021  107 
2.  38254  PhD Špela Gradišar  Materials science and technology  Junior researcher  2018 - 2020  18 
3.  37907  PhD Sarah Jurjevec  Materials science and technology  Technical associate  2018 - 2019  25 
4.  28412  PhD Sebastijan Kovačič  Chemical engineering  Researcher  2018 - 2021  177 
5.  52221  Maša Masič    Technical associate  2019 - 2020 
6.  29613  PhD David Pahovnik  Materials science and technology  Researcher  2018 - 2021  189 
7.  12048  PhD Marjetka Podobnik  Biochemistry and molecular biology  Researcher  2018 - 2021  317 
8.  17270  Polona Prosen    Technical associate  2020 - 2021 
9.  29676  Jasmina Turnšek  Materials science and technology  Technical associate  2021 
10.  50609  PhD Petra Utroša  Materials science and technology  Junior researcher  2018 - 2021  38 
11.  12318  PhD Ema Žagar  Materials science and technology  Head  2018 - 2021  484 
Organisations (1)
no. Code Research organisation City Registration number No. of publicationsNo. of publications
1.  0104  National Institute of Chemistry  Ljubljana  5051592000  20,996 
Abstract
Scaffolds with rationally designed chemical composition and structure have promising potential for application in cell culture, regenerative medicine, and tissue engineering. Such scaffolds need to mimic the hierarchical structure of natural tissues in order to provide the required structural and mechanical framework. Furthermore, biomimetic scaffolds need to display the necessary biochemical and signalling cues for cellular function. So far, various types of macromolecules have been used for scaffold preparation, including natural polysaccharides and proteins, as well as various synthetic polymers based on vinyl monomers and polyesters. However, the major drawbacks of currently existing scaffolds are associated with inappropriate degradability, biocompatibility and surface functionality in the case of scaffold based on synthetic polymers and, on the other hand, with poor mechanical properties and batch-to-batch variation in scaffold quality in the case of those prepared from natural biopolymers. Thus, there is an ongoing demand to engineer functional three-dimensional (3D) scaffolds with advanced properties. In this respect, polyHIPE materials prepared by high internal phase emulsion (HIPE) templating are very attractive synthetic scaffolds with clear benefits associated with the unique interconnected porous structure, providing pathways for cell migration, proliferation and vascularization due to effective transportation of fluids carrying nutrients, gasses, and metabolic waste. However, till now HIPE templating has been mainly limited to non-degradable synthetic polymers. Synthetic polypeptides, prepared by ring opening polymerization (ROP) of cyclic N-carboxyanhydride (NCA) monomers, are on the other hand distinguished by all the desired chemical properties a material used for the 3D scaffolding should possess since they combine the modular nature of synthetic polymers together with inherent biocompatibility and biodegradability of natural polymers. However, so far they have not been prepared in the form of scaffolds with controlled morphology suitable for optimal cell growth. There is thus a niche for advanced macroporous, synthetic biomimetic scaffolds that would combine all key requirements to support the 3D cell growth and enable the integration with living cells. This challenge will be approached through the design, fabrication, and characterization of synthetic polypeptide-based polyHIPE scaffolds with unique 3D interconnected porous structure, varying chemical composition, degradation rate, and suitable mechanical properties by employing two different synthetic approaches. In the first approach linear polypeptides of different chemical composition will be first synthesized, which will be afterwards cross-linked in HIP emulsion to prepare the soft polypeptide polyHIPE hydrogels. On the other hand, the second approach will apply ROP of NCAs directly in the continuous phase of HIP emulsion using NCA-based cross-linkers to prepare the solid polypeptide-based polyHIPEs. For this purpose, the choice of a suitable combination of the HIPE type (water-in-oil (W/O), oil-in-water (O/W) or oil-in-oil (O/O) emulsion), and ROP of the appropriately selected NCAs will be studied. The merits of the newly developed synthetic polypeptide-based polyHIPE scaffolds will be assessed through the in vitro studies. Moreover, we will focus on establishing and understanding the relationships between the synthesis, structure, properties, and scaffold function during cell culture in order to assess the perspectives for “bottom-up” and “top-down” designed strategies for the production of emulsion templated synthetic polypeptide scaffolds suitable for tissue engineering. Ultimately, this project is expect to result in a new generation of scaffolds which will integrate all the necessary properties that high-performance scaffolds should have for cell culturing and tissue engineering.
Significance for science
The proposed project discloses a promising alternative to currently available 3D scaffolds for cell culturing, tissue engineering and regenerative medicine since it offers clear benefits by combining morphological features of polyHIPE materials with unique properties of synthetic polypeptides. Such a combination is until now an unsolved challenge yet, and thus, the proposed project’s outcomes go beyond the current state-of-the-art in this scientific field. The resulting high performance emulsion-templated synthetic polypeptide-based polyHIPE scaffolds that intended to be developed in this project, present advanced polymeric scaffolds hitherto unexplored. Such scaffolds will integrate all important properties in a single piece material needed to create functional and implantable, biodegradable scaffold, and therefore, they will represent a new generation of biocompatible and biodegradable macroporous scaffolds distinguished by appropriate architecture, dimensional stability and suitable functionality. The results expected from the proposed research project will be relevant to the development of polymer science since high performance polyHIPE scaffolds based on synthetic polypeptides are intended to be prepared by a new synthetic methodology involving ring opening polymerization of N-carboxyanhydrides monomers within a continuous phase of the HIPE which has not been tackled yet, and remains a major challenge to polymer scientists. We expect that findings acquired during the project execution will be, due to multidisciplinary nature of the project, relevant also to colloid, material, and biochemistry scientific community. Last but not least, relevance of the results expected from the proposed research project will be important not only for the development of basic science, but also from the applicative point of view since degradable macroporous scaffolds with well-defined morphology and functionality follow the demands for new materials and technologies in biomedical applications, especially for cell culturing, tissue engineering and regenerative medicine. The project’s outcomes will have a significant impact on enforcement of macroporous scaffolds in a very competitive and rapidly growing field of polymeric scaffold design for tissue engineering. The results of the proposed project might have also a great market potential due to an economically attractive process that will be used for the preparation of synthetic polypeptide-based polyHIPEs. Different market analyses in bone tissue engineering for example show the increased demand for bone grafts substitutes. For example, the EU market for bone graft substitute products was valued at $177 million in 2010 and is expected to rise 17 percent annually, reaching the value of $461 million in 2016 as predicted by the MedTech Insight.[ M. A. Velasco et al., Biomed Res Inter 2015, 729076]
Significance for the country
The proposed project discloses a promising alternative to currently available 3D scaffolds for cell culturing, tissue engineering and regenerative medicine since it offers clear benefits by combining morphological features of polyHIPE materials with unique properties of synthetic polypeptides. Such a combination is until now an unsolved challenge yet, and thus, the proposed project’s outcomes go beyond the current state-of-the-art in this scientific field. The resulting high performance emulsion-templated synthetic polypeptide-based polyHIPE scaffolds that intended to be developed in this project, present advanced polymeric scaffolds hitherto unexplored. Such scaffolds will integrate all important properties in a single piece material needed to create functional and implantable, biodegradable scaffold, and therefore, they will represent a new generation of biocompatible and biodegradable macroporous scaffolds distinguished by appropriate architecture, dimensional stability and suitable functionality. The results expected from the proposed research project will be relevant to the development of polymer science since high performance polyHIPE scaffolds based on synthetic polypeptides are intended to be prepared by a new synthetic methodology involving ring opening polymerization of N-carboxyanhydrides monomers within a continuous phase of the HIPE which has not been tackled yet, and remains a major challenge to polymer scientists. We expect that findings acquired during the project execution will be, due to multidisciplinary nature of the project, relevant also to colloid, material, and biochemistry scientific community. Last but not least, relevance of the results expected from the proposed research project will be important not only for the development of basic science, but also from the applicative point of view since degradable macroporous scaffolds with well-defined morphology and functionality follow the demands for new materials and technologies in biomedical applications, especially for cell culturing, tissue engineering and regenerative medicine. The project’s outcomes will have a significant impact on enforcement of macroporous scaffolds in a very competitive and rapidly growing field of polymeric scaffold design for tissue engineering. The results of the proposed project might have also a great market potential due to an economically attractive process that will be used for the preparation of synthetic polypeptide-based polyHIPEs. Different market analyses in bone tissue engineering for example show the increased demand for bone grafts substitutes. For example, the EU market for bone graft substitute products was valued at $177 million in 2010 and is expected to rise 17 percent annually, reaching the value of $461 million in 2016 as predicted by the MedTech Insight.[ M. A. Velasco et al., Biomed Res Inter 2015, 729076]
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