clickECM: Development of a cell-derived extracellular matrix with azide functionalities

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2017
Autor:innen
Ruff, S. M.
Keller, Silke
Tovar, Günter
Bach, Monika
Kluger, Petra
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Acta Biomaterialia. 2017, 52, pp. 159-170. ISSN 1742-7061. eISSN 1878-7568. Available under: doi: 10.1016/j.actbio.2016.12.022
Zusammenfassung

In vitro cultured cells produce a complex extracellular matrix (ECM) that remains intact after decellularization. The biological complexity derived from the variety of distinct ECM molecules makes these matrices ideal candidates for biomaterials. Biomaterials with the ability to guide cell function are a topic of high interest in biomaterial development. However, these matrices lack specific addressable functional groups, which are often required for their use as a biomaterial. Due to the biological complexity of the cell-derived ECM, it is a challenge to incorporate such functional groups without affecting the integrity of the biomolecules within the ECM. The azide-alkyne cycloaddition (click reaction, Huisgen-reaction) is an efficient and specific ligation reaction that is known to be biocompatible when strained alkynes are used to avoid the use of copper (I) as a catalyst. In our work, the ubiquitous modification of a fibroblast cell-derived ECM with azides was achieved through metabolic oligosaccharide engineering by adding the azide-modified monosaccharide Ac4GalNAz (1,3,4,6-tetra-O-acetyl-N-azidoacetylgalactosamine) to the cell culture medium. The resulting azide-modified network remained intact after removing the cells by lysis and the molecular structure of the ECM proteins was unimpaired after a gentle homogenization process. The biological composition was characterized in order to show that the functionalization does not impair the complexity and integrity of the ECM. The azides within this "clickECM" could be accessed by small molecules (such as an alkyne-modified fluorophore) or by surface-bound cyclooctynes to achieve a covalent coating with clickECM.

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Fachgebiet (DDC)
540 Chemie
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Cell-derived extracellular matrix; Metabolic oligosaccharide engineering; Biorthogonal click chemistry; Surface modification; Tissue engineering
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ISO 690RUFF, S. M., Silke KELLER, Daniel E. WIELAND, Valentin WITTMANN, Günter TOVAR, Monika BACH, Petra KLUGER, 2017. clickECM: Development of a cell-derived extracellular matrix with azide functionalities. In: Acta Biomaterialia. 2017, 52, pp. 159-170. ISSN 1742-7061. eISSN 1878-7568. Available under: doi: 10.1016/j.actbio.2016.12.022
BibTex
@article{Ruff2017-04-01click-37431,
  year={2017},
  doi={10.1016/j.actbio.2016.12.022},
  title={clickECM: Development of a cell-derived extracellular matrix with azide functionalities},
  volume={52},
  issn={1742-7061},
  journal={Acta Biomaterialia},
  pages={159--170},
  author={Ruff, S. M. and Keller, Silke and Wieland, Daniel E. and Wittmann, Valentin and Tovar, Günter and Bach, Monika and Kluger, Petra}
}
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