Impact of UV- and carbodiimide-based crosslinking on the integrin-binding properties of collagen-based materials.
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Bax, D., Davidenko, N., Hamaia, S., Farndale, R., Best, S., & Cameron, R. (2019). Impact of UV- and carbodiimide-based crosslinking on the integrin-binding properties of collagen-based materials.. Acta biomaterialia, 100 280-291. https://doi.org/10.1016/j.actbio.2019.09.046
Collagen constructs are widely used for tissue engineering. These are frequently chemically crosslinked, using EDC, to improve their stability and tailor their physical properties. Although generally biocompatible, chemical crosslinking can modify crucial amino acid side chains, such as glutamic acid, that are involved in integrin-mediated cell adhesion. Instead UV crosslinking modifies aromatic side chains. Here we elucidate the impact that EDC, in combination with UV, exerts on the activity of integrin-binding motifs. By employing a model cell line that exclusively utilises integrin α2β1, we found that whilst EDC crosslinking modulated cell binding, from cation-dependent to cation-independent, UV-mediated crosslinking preserved native-like cell binding, proliferation and surface colonisation. Similar results were observed using a purified recombinant I-domain from integrin α1. Conversely, binding of the I-domain from integrin α2 was sensitive to UV, particularly at low EDC concentrations. Therefore, from this in vitro study, it appears that UV can be used to augment EDC whist retaining a specific subset of integrin-binding motifs in the native collagen molecule. These findings, delineating the EDC- and UV-susceptibility of cell-binding motifs, permit controlled cell adhesion to collagen-based materials through specific integrin ligation in vitro. However, in vivo, further consideration of the potential response to UV wavelength and dose is required in the light of literature reports that UV initiated collagen scission may lead to an adverse inflammatory response.
Cell Line, Tumor, Animals, Cattle, Humans, Carbodiimides, Collagen, Integrin alpha2beta1, Biocompatible Materials, Cross-Linking Reagents, Ultraviolet Rays, Cell Adhesion, Cell Proliferation, Cell Movement, Protein Binding, Platelet Adhesiveness, Protein Domains
The authors would like to thank the EPSRC [Fellowship EP/N019938/1] the ERC [Advanced Grant 320598 3D-E] and the British Heart Foundation [Special Project SP/15/7/31561] for providing financial support for this project. DVB was funded by the People's Programme of the EU 7th Framework Programme [RAE no: PIIF-GA-2013-624904].
European Research Council (320598)
British Heart Foundation (SP/15/7/31561)
European Commission (624904)
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External DOI: https://doi.org/10.1016/j.actbio.2019.09.046
This record's URL: https://www.repository.cam.ac.uk/handle/1810/297428
Attribution-NonCommercial-NoDerivatives 4.0 International
Licence URL: https://creativecommons.org/licenses/by-nc-nd/4.0/