Hostname: page-component-cd9895bd7-q99xh Total loading time: 0 Render date: 2024-12-23T23:52:09.490Z Has data issue: false hasContentIssue false
  • English
  • Français

Immuno-compatibility of desaminotyrosine and desaminotyrosyl tyrosine functionalized star-shaped oligo(ethylene glycol)s with different molecular weights

Published online by Cambridge University Press:  08 April 2015

Toralf Roch ,
Konstanze K. Julich-Gruner ,
Axel T. Neffe ,
Nan Ma  and
Andreas Lendlein
Toralf Roch
Affiliation:
Institute of Biomaterial Science and Berlin-Brandenburg Center for Regenerative Therapies (BCRT), Helmholtz-Zentrum Geesthacht, Kantstr. 55, 14513 Teltow, Germany; Helmholtz Virtual Institute − Multifunctional Biomaterials for Medicine, Teltow and Berlin, Germany;
Konstanze K. Julich-Gruner
Affiliation:
Institute of Biomaterial Science and Berlin-Brandenburg Center for Regenerative Therapies (BCRT), Helmholtz-Zentrum Geesthacht, Kantstr. 55, 14513 Teltow, Germany;
Axel T. Neffe
Affiliation:
Institute of Biomaterial Science and Berlin-Brandenburg Center for Regenerative Therapies (BCRT), Helmholtz-Zentrum Geesthacht, Kantstr. 55, 14513 Teltow, Germany; Helmholtz Virtual Institute − Multifunctional Biomaterials for Medicine, Teltow and Berlin, Germany;
Nan Ma
Affiliation:
Institute of Biomaterial Science and Berlin-Brandenburg Center for Regenerative Therapies (BCRT), Helmholtz-Zentrum Geesthacht, Kantstr. 55, 14513 Teltow, Germany; Helmholtz Virtual Institute − Multifunctional Biomaterials for Medicine, Teltow and Berlin, Germany; Institute of Chemistry and Biochemistry, Department of Biology, Chemistry and Pharmacy, Freie Universität Berlin, Takustr. 3, 14195 Berlin, Germany
Andreas Lendlein
Affiliation:
Institute of Biomaterial Science and Berlin-Brandenburg Center for Regenerative Therapies (BCRT), Helmholtz-Zentrum Geesthacht, Kantstr. 55, 14513 Teltow, Germany; Helmholtz Virtual Institute − Multifunctional Biomaterials for Medicine, Teltow and Berlin, Germany; Institute of Chemistry and Biochemistry, Department of Biology, Chemistry and Pharmacy, Freie Universität Berlin, Takustr. 3, 14195 Berlin, Germany
Get access

Abstract

Polymer-based therapeutic strategies require biomaterials with properties and functions tailored to the demands of specific applications leading to an increasing number of newly designed polymers. For the evaluation of those new materials, comprehensive biocompatibility studies including cyto-, tissue-, and immunocompatibility are essential. Recently, it could be demonstrated that star-shaped amino oligo(ethylene glycol)s (sOEG) with a number average molecular weight of 5 kDa and functionalized with the phenol-derived moieties desaminotyrosine (DAT) or desaminotyrosyl tyrosine (DATT) behave in aqueous solution like surfactants without inducing a substantial cytotoxicity, which may qualify them as solubilizer for hydrophobic drugs in aqueous solution. However, for biomedical applications the polymer solutions need to be free of immunogenic contaminations, which could result from inadequate laboratory environment or contaminated starting material. Furthermore, the materials should not induce uncontrolled or undesired immunological effects arising from material intrinsic properties. Therefore, a comprehensive immunological evaluation as perquisite for application of each biomaterial batch is required. This study investigated the immunological properties of sOEG-DAT(T) solutions, which were prepared using sOEG with number average molecular weights of 5 kDa, 10 kDa, and 20 kDa allowing analyzing the influence of the sOEG chain lengths on innate immune mechanisms. A macrophage-based assay was used to first demonstrate that all DAT(T)-sOEG solutions are free of endotoxins and other microbial contaminations such as fungal products. In the next step, the capacity of the different DAT(T)-functionalized sOEG solutions to induce cytokine secretion and generation of reactive oxygen species (ROS) was investigated using whole human blood. It was observed that low levels of the pro-inflammatory cytokines interleukin(IL)-1β and IL-6 were detected for all sOEG solutions but only when used at concentrations above 250 µg·mL-1. Furthermore, only the 20 kDa sOEG-DAT induced low amounts of ROS-producing monocytes. Conclusively, the data indicate that the materials were not contaminated with microbial products and do not induce substantial immunological adverse effects in vitro, which is a prerequisite for future biological applications.

Keywords

biomedicalbiomaterialpolymer
Type
Articles
Information
MRS Online Proceedings Library (OPL) , Volume 1718: Symposium B – Multifunctional Polymeric and Hybrid Materials , 2015 , pp. 97 - 102
Copyright
Copyright © Materials Research Society 2015 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

REFERENCES

Lu, Y. and Park, K., Int. J. Pharm., 453, 198 (2013).CrossRefGoogle Scholar
Tan, C., Wang, Y., and Fan, W., Pharmaceutics, 5, 201 (2013).CrossRefGoogle Scholar
Julich-Gruner, K. K., Neffe, A. T., and Lendlein, A., J. Appl. Biomater. Funct. Mater., 10, 170 (2012).Google Scholar
Julich-Gruner, K. K., Roch, T., Ma, N., Neffe, A.T., Lendlein, A., Immunological investigations of oligoethylene glycols functionalized with desaminotyrosine and desaminotyrosyltyrosine, Mater. Res. Soc. Symp. Proc. 1569, 9–14 (2013)CrossRefGoogle Scholar
Roch, T., Schulz, C., Jung, F., Ma, N., and Lendlein, A., Clin. Hemorheol. Microcirc., 57, 203 (2014).Google Scholar
Berg, B., Solberg, H., Nilsson, J., and Tryding, N., in: Reference Values in Laboratory Medicine. The Current State of the Art, edited by Gräsbeck, R. and Alström, T. (John Wiley & Sons, Chichester, 1981), pp. 55–64.Google Scholar
Ulbricht, J., Jordan, R., and Luxenhofer, R., Biomaterials, 35, 4848 (2014).CrossRefGoogle Scholar
Kader, K. N. and Coyle, C. H., J. Biomed. Mater. Res. B Appl. Biomater., 83, 138 (2007).CrossRefGoogle Scholar
Amulic, B., Cazalet, C., Hayes, G. L., Metzler, K. D., and Zychlinsky, A., Annu. Rev. Immunol., 30, 459 (2012).CrossRefGoogle Scholar