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Immunological investigations of oligoethylene glycols functionalized with desaminotyrosine and desaminotyrosyltyrosine

Published online by Cambridge University Press:  02 July 2013

Konstanze K. Julich-Gruner ,
Toralf Roch ,
Nan Ma ,
Axel T. Neffe  and
Andreas Lendlein
Konstanze K. Julich-Gruner
Affiliation:
Institute of Biomaterial Science and Berlin-Brandenburg Centre for Regenerative Therapies, Helmholtz-Zentrum Geesthacht, Kantstrasse 55, 14513 Teltow, Germany
Toralf Roch
Affiliation:
Institute of Biomaterial Science and Berlin-Brandenburg Centre for Regenerative Therapies, Helmholtz-Zentrum Geesthacht, Kantstrasse 55, 14513 Teltow, Germany
Nan Ma
Affiliation:
Institute of Biomaterial Science and Berlin-Brandenburg Centre for Regenerative Therapies, Helmholtz-Zentrum Geesthacht, Kantstrasse 55, 14513 Teltow, Germany
Axel T. Neffe
Affiliation:
Institute of Biomaterial Science and Berlin-Brandenburg Centre for Regenerative Therapies, Helmholtz-Zentrum Geesthacht, Kantstrasse 55, 14513 Teltow, Germany
Andreas Lendlein
Affiliation:
Institute of Biomaterial Science and Berlin-Brandenburg Centre for Regenerative Therapies, Helmholtz-Zentrum Geesthacht, Kantstrasse 55, 14513 Teltow, Germany
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Abstract

Biomaterials require thorough in vitro testing before being applied in vivo. Unwanted contaminations of biomaterials but also their intrinsic properties can cause uncontrolled immune response leading to severe consequences for the patient. Therefore, immunological evaluation of materials for biomedical applications is mandatory before entering clinical application. In order to introduce physical netpoints, the aromatic compounds desaminotyrosine (DAT) and desaminotyrosyl-tyrosine (DATT) were successfully used to functionalize linear and star-shaped oligoethylene glycol (lOEG and sOEG) as previously described. The materials showed properties of surfactants and have potential to be used for solubilization of lipophilic drugs in water. Furthermore, the materials are susceptible for H2O2 degradation as determined by MALDI-ToF MS analyses. This is important for potential in vivo applications, as macrophages can release reactive oxygen species (ROS) under inflammatory conditions. As it is known that surfactant solutions of high concentration can lead to cell lysis, the effects of OEG-DAT(T) solutions on murine RAW macrophages were investigated. Even at highest OEG-DAT(T) concentration of 1000 µg·mL-1 the viability of the RAW cells was not significantly impaired. Additionally, the polymers were incubated with whole human blood and the production of inflammatory cytokines such as the tumor necrosis factor (TNF)-α and interleukin (IL)-6 was determined. Only at high concentrations, the OEG-DAT(T) solution induced low levels of TNF-α and IL-6, indicating that a mild inflammatory reaction could be expected when such high OEG-DAT(T) concentrations are applied in vivo. Similarly, the OEG-DAT(T) solution did not induce ROS in monocytes and neutrophils after incubation with whole human blood. Conclusively, the data presented here demonstrate that OEG-DAT(T) do not lead to a substantial activation of the innate immune mechanisms and could therefore be investigated for solubilizing pharmaceutical agents.

Keywords

biomaterialpolymerbiological
Type
Articles
Information
MRS Online Proceedings Library (OPL) , Volume 1569: Symposium NN – Advanced Materials for Biological and Biomedical Applications , 2013 , pp. 9 - 14
Copyright
Copyright © Materials Research Society 2013 

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References

REFERENCES

Opal, S.M., Contrib Nephrol, 167, 14 (2010).CrossRefGoogle Scholar
Roch, T., Pierce, B.F., Zaupa, A., Jung, F., Neffe, A.T., and Lendlein, A., Macromol Symp, 309-310, 182 (2011).CrossRefGoogle Scholar
Zaupa, A., Neffe, A.T., Pierce, B.F., Nöchel, U., and Lendlein, A., Biomacromolecules, 12, 75 (2011).CrossRefGoogle Scholar
Julich-Gruner, K.K., Neffe, A.T., and Lendlein, A., J. Appl. Biomater. Function. Mater., 10, 170 (2012).Google Scholar
Roch, T., Cui, J., Kratz, K., Lendlein, A., and Jung, F., Clin Hemorheol Microcirc, 50, 131 (2012).Google Scholar
Wischke, C., Mathew, S., Roch, T., Frentsch, M., and Lendlein, A., J Control Release, 164, 299 (2012).10.1016/j.jconrel.2012.06.034CrossRefGoogle Scholar
Berg, B., Solberg, H., Nilsson, J., and Tryding, N., John Wiley & Sons Chichester (UK), 55 (1981).Google Scholar
Gräsbeck, R., Alström, T., and N. workshop, Wiley, Chichester.Google Scholar
Lange, M., Braune, S., Luetzow, K., Richau, K., Scharnagel, N., Weinhart, M., Neffe, A.T., Jung, F., Haag, R., and Lendlein, A., Macromol. Rapid Commun., 33, 1487 (2012).CrossRefGoogle Scholar
Zanoni, I., Ostuni, R., Capuano, G., Collini, M., Caccia, M., Ronchi, A.E., Rocchetti, M., Mingozzi, F., Foti, M., Chirico, G., Costa, B., Zaza, A., Ricciardi-Castagnoli, P., and Granucci, F., Nature, 460, 264 (2009).CrossRefGoogle Scholar
Quinn, M.T. and Schepetkin, I.A., J Innate Immun, 1, 509 (2009).CrossRefGoogle Scholar