Cross-linking and decoration of polysialic acid

• Applicant: Professor Dr. Andreas Kirschning
• Subject Area: Biological and Biomimetic Chemistry ; Organic Molecular Chemistry - Synthesis and Characterisation
• Term: from 2004 to 2012
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 5471076

• Final Report Year: 2014

Final Report Abstract

Various polysialic acid derivatives have been prepared, such as azide and alkyne functionalized polysialic acid, methacrylated polysialic acid and aldehyde functionalized polysialic acid. The modified polysialic acid derivatives were used to prepare hydrogels, which were studied as cellular scaffolds for neural tissue engineering. Polysialic acid based hydrogels were formed via different crosslinking methods. Azide and alkyne decorated polysialic acid derivatives were used as “clickable” macromolecular precursors and in the presence of Cu-catalyst. Since copper is potentially cytotoxic for organisms, the metal-free “click” linkage is more favored for generation of polysialic acid hydrogels. Together with the corresponding azides, oxanorbornadiene modified polysialic acid created hydrogel without any addition catalyst or reagent. Photo-induced radical crosslinking is also an appropriate approach for the preparation of hydrogels using methacrylated polymers. Finally, hydrazone linked polysialic acid hydrogels have been synthesized, which turned out to be instable and liquefied after a few hours. Nevertheless, blends of aldehyde modified polySia and hydrazide decorated alginate or hyaluronate can generate very stable and flexible hydrogels. In order to improve cell adhesion, polysialic acid was decorated with RGD-peptides via “click” reaction or imine formation. These hydrogels were also tested in cell cultures but surprisingly no significant improvement of cell adhesion could be detected. In this project, neuraminic acid was successfully modified at two positions (C-1 and C-5) with various functional groups. C-1 modification was accomplished via coupling of neuraminic acid and 3-azidopropan-1-amine or propargylamine. N-acyl derivatizations were established from various substituents and deacetylated neuraminic acid. At first, the substituents were transferred into their corresponding NHS-ester. Subsequently, the NHS-esters were coupled to the amino group of neuraminic acid to afford different neuraminic acid derivatives. Finally, methacrylate modified neuraminic acid was synthesized directly from methacrylic anhydride and deacetylated neuraminic acid under mild conditions.

Publications

• Chemical decoration of polysialic acid using “click”chemistry. 18. Nachwuchswissenschaftler-Symposium ”Bioorganische Chemie”, Hannover, Germany, 28. – 30.09.2009
  Y. Su, J. Palecek, A. Kirschning, G. Dräger
  
• (2010) Carbohydrates. In: Handbook of Biodegradable Polymers, Schröter, M.; Lendlein, A. (Eds.), Wiley-VCH, Weinheim, pp 155-193
  G. Dräger, S. Dumitriu, A. Krause, L. Möller, L.
  
• (2010). Fiber scaffolds of polysialic acid via electrospinning for peripheral nerve regeneration. J. Mater. Sci. Mater. Med., 21, 2115-2124
  Assmann, U., Szentivanyi, A., Stark, Y., Scheper, T., Berski, S., Dräger, G., and Schuster, R.H.
  
• (2010). In vivo evaluation of polysialic acid as part of tissue-engineered nerve transplants. Tissue Eng Part A, 16, 3085-3098
  Haastert-Talini, K., Schaper-Rinkel, J., Schmitte, R., Bastian, R., Mühlenhoff, M., Schwarzer, D., Dräger, G., Su, Y., Scheper, T., Gerardy-Schahn, R., and Grothe, C.
  
• (2010). Synthesis of new polysialic acid derivatives. Macromol. Biosci., 10, 1028-1033
  Su, Y., Kasper, C., Kirschning, A., Dräger, G., and Berski, S.
  
• Chemical Modification of Polysialic Acid for the Production of Scaffold Materials for Tissue Engineering. 459. WE-Heraeus-Seminar: Degradable Polymers as Biomaterials, Bad Honnef, Germany, 30.05 - 02 06.2010
  Y. Su, P. Krohn, A. Kirschning, G. Dräger
  
• Synthesis of PolySia Scaffold material for Tissue Engineering using “Click” chemistry. i-PolyMat 2010, Kerkrade, Netherland, 16 - 19 May 2010
  Y. Su, A. Kirschning, G. Dräger
  
• Towards Biocomaptible Medical Devices: Functionalization of TPX with RGD Peptides. Europolymer Conference 2011, Gargnano, Italy, 29.05-03.06.2011. Sialoglyco 2010, Potsdam, Germany, 21.-26.08.2010
  L. Möller, C. Hess, J. Paleček, Y. Su, A. Haverich, A. Kirschning, G. Dräger
  
• Functionalization of Polysialic Acid Towards 3DScaffold for the Application in Tissue Engineering. Europolymer Conference 2011, Gargnano, Italy, 29.05-03.06.2011
  Y. Su, J. Paleček, A. Kirschning, G. Dräger
  
• Immobilization of polysialic acid on nanoporous silica particles. European Society for Biomaterials 2011, Dublin, Ireland 4.-8.9.2011
  A. Neumann, S. Böhm, I. Bice, T. Scheper, A. Christel, S. Williams, P. Behrens, Y. Su, G. Dräger, A. Kirschning, U. Wangenheim, R. Schuster, R. Gerady-Schahn, C. Kasper
  
• (2013). Copper mediated and copper free click decoration of polysialic acid for RGD-modification and hydrogel formation. Macromolecular Symposia, 334, 82-91
  Su, Y., Palecek, J., Kirschning, A., and Dräger, G.
  
• (2013). Towards a biocompatible artificial lung: Covalent functionalization of poly(4-methylpent-1-ene) (TPX) with cRGD pentapeptide. Beilstein. J. Org. Chem., 9, 270-277
  Möller, L., Hess, C., Palecek, J., Su, Y., Haverich, A., Kirschning, A., and Dräger, G.