Project Details
Projekt
FOR 548: Polysialic Acid: Towards the Evaluation of a New, Bio-identical Scaffold Material
Subject Area
Chemistry
Medicine
Thermal Engineering/Process Engineering
Medicine
Thermal Engineering/Process Engineering
Term
from 2004 to 2010
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 5471076
The rapidly growing knowledge and technical expertise in the field of transplantation medicine is paralleled by an urgent lack in organ availability and all projections indicate that this gap will continue to widen. A new interdisciplinary field "tissue engineering" has developed, attempting the de novo creation of organ substitutes. Crucial in tissue engineering strategies is the reconstruction of the organs complex three-dimensional architecture, where numerous specialised zones are combined to a functional "mosaic" and combined with extended capillary and neuronal networks.
Because normal cells in culture are unable to orient in three dimensions to reconstitute the tissue, the formation of artificial organs requires growth supports, the so called scaffolds. Scaffolds are essential to shape the organ structure and to provide the matrix for cells to attach to and proliferate. Moreover, scaffolds are required to physically integrate other tissues like nerves and vessels, which are required for function and nutrition of the transplant. On the other hand scaffolds may interfere with the function of the organ and therefore should not be permanent. The biodegradation of scaffolds is essential to release an autonomous organ. Ideally the breakdown of scaffolds parallels the process of organ formation. This in turn implies that the generated breakdown products must be inert to not harm the artificial organ. In fact, the search for scaffolding materials that fulfill this request of full biocompatibility and simultaneously have sufficient physico-chemical stability for being tailored into two- or three-dimensional objects is a major challenge in tissue engineering.
We suggest the testing of polysialic acid as putative scaffold material. Polysialic acid is a sugar polymer found as a component of neuronal tissue in all higher vertebrates. The biosynthesis of polysialic acid has been intensively studied and all enzymes involved in the reaction cascade have been cloned and are available to produce recombinant polysialic acid "in vitro". The multi-functionality of the sugar polymer, its long half-life in the circulation, and chemical versatility make it a most promising substrate in tissue engineering approaches. Polysialic acid specific phage born enzymes exist and enable the induced and controlled degradation of the polymer. Sugar oligomers that are products in the degradation reaction provide valuable nutrients for all animal cells.
Because normal cells in culture are unable to orient in three dimensions to reconstitute the tissue, the formation of artificial organs requires growth supports, the so called scaffolds. Scaffolds are essential to shape the organ structure and to provide the matrix for cells to attach to and proliferate. Moreover, scaffolds are required to physically integrate other tissues like nerves and vessels, which are required for function and nutrition of the transplant. On the other hand scaffolds may interfere with the function of the organ and therefore should not be permanent. The biodegradation of scaffolds is essential to release an autonomous organ. Ideally the breakdown of scaffolds parallels the process of organ formation. This in turn implies that the generated breakdown products must be inert to not harm the artificial organ. In fact, the search for scaffolding materials that fulfill this request of full biocompatibility and simultaneously have sufficient physico-chemical stability for being tailored into two- or three-dimensional objects is a major challenge in tissue engineering.
We suggest the testing of polysialic acid as putative scaffold material. Polysialic acid is a sugar polymer found as a component of neuronal tissue in all higher vertebrates. The biosynthesis of polysialic acid has been intensively studied and all enzymes involved in the reaction cascade have been cloned and are available to produce recombinant polysialic acid "in vitro". The multi-functionality of the sugar polymer, its long half-life in the circulation, and chemical versatility make it a most promising substrate in tissue engineering approaches. Polysialic acid specific phage born enzymes exist and enable the induced and controlled degradation of the polymer. Sugar oligomers that are products in the degradation reaction provide valuable nutrients for all animal cells.
DFG Programme
Research Units
Projects
- Biotechnological production; protein engineering (Applicants Gerardy-Schahn, Rita ; Scheper, Thomas )
- Characterization of material properties of polysialic acids (Applicant Bormann, Dirk )
- Cross-linking and decoration of polysialic acid (Applicant Kirschning, Andreas )
- Development of techniques for the production of 2D- and 3D-solids from polysialic acids and characterization of hierarchic self-organization structures (Applicant Schuster, Robert H. )
- Immobilization of polysialic acid on the surfaces of biometerials (Applicant Behrens, Peter )
- In vivo application of polySia-based materials in a rat model of peripheral nerve regeneration - Impact on morphological and functional regeneration (Applicant Grothe, Claudia )
- Interacitve testing and optimization of polySia matrices effects on cell systems based on DNA microarray techniques (Applicant Scheper, Thomas )
- Koordination der Forschungsgruppe 548 (Applicant Gerardy-Schahn, Rita )
- Modification of polysialic acid by derivatization and mineralization (Applicant Behrens, Peter )
- Purification and recombinant production of polysialic acid (Applicant Scheper, Thomas )
- Purification and recombinant production of polysialic acid (Applicant Kirschning, Andreas )
- Static and dynamic cultivation conditions to characterise matrix qualities of simple and complex polySia-based materials. Monitoring of cell parameters by DNA microarray and cell biological methods (Applicants Grothe, Claudia ; Kasper, Cornelia )
- Studies on the controlled degradation of polySia scaffolds (Applicant Gerardy-Schahn, Rita )
- Towards 3rd generation scaffolds: Enzyme design for in vitro production of natural and functionalized spolySia (Applicant Gerardy-Schahn, Rita )
Spokesperson
Professorin Dr. Rita Gerardy-Schahn
