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

  • 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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Metadaten
Name:Kluger, Petra
DOI:https://doi.org/10.1016/j.actbio.2016.12.022
ISSN:1742-7061
eISSN:1878-7568
Erschienen in:Acta biomaterialia : structure, property, function ; relationships in biomaterials
Publisher:Elsevier
Place of publication:Amsterdam
Document Type:Article
Language:English
Year of Publication:2017
Tag:biorthogonal click chemistry; cell-derived extracellular matrix; metabolic oligosaccharide engineering; surface modification; tissue engineering
Volume:52
Pagenumber:12
First Page:159
Last Page:170
Dewey Decimal Classification:540 Chemie
Open Access:Nein
Licence (German):License Logo  Lizenzbedingungen Elsevier