Control of Crosslinking for Tailoring Collagen-based Scaffolds Stability and Mechanics
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Davidenko, N., Schuster, C., Bax, D., Raynal, N., Farndale, R., Best, S., & Cameron, R. (2015). Control of Crosslinking for Tailoring Collagen-based Scaffolds Stability and Mechanics. Acta Biomaterialia, 25 131-142. https://doi.org/10.1016/j.actbio.2015.07.034
We provide evidence to show that the standard reactant concentrations used in tissue engineering to cross-link collagen-based scaffolds are up to 100 times higher than required for mechanical integrity in service, and stability against degradation in an aqueous environment. We demonstrate this with a detailed and systematic study by comparing scaffolds made from (a) collagen from two different suppliers, (b) gelatin (a partially denatured collagen) and (c) 50% collagen-50% gelatin mixtures. The materials were processed, using lyophilisation, to produce homogeneous, highly porous scaffolds with isotropic architectures and pore diameters ranging from 130-260m. Scaffolds were cross-linked using a carbodiimide treatment, to establish the effect of the variations in crosslinking conditions (down to very low concentrations) on the morphology, swelling, degradation and mechanical properties of the scaffolds. Carbodiimide concentration of 11.5mg/ml was defined as the standard (100%) and was progressively diluted down to 0.1%. It was found that 10fold reduction in the carbodiimide content led to the significant increase (almost 4fold) in the amount of free amine groups (primarily on collagen lysine residues) without compromising mechanics and stability in water of all resultant scaffolds. The importance of this finding is that, by reducing cross-linking, the corresponding cell-reactive carboxylate anions (collagen glutamate or aspartate residues) that are essential for integrin-mediated binding remain intact. Indeed, a 10-fold reduction in carbodiimide crosslinking resulted in near native-like cell attachment to collagen scaffolds. We have demonstrated that controlling the degree of cross-linking, and hence retaining native scaffold chemistry, offers a major step forward in the biological performance of collagen- and gelatin-based tissue engineering scaffolds.
Tissue engineering, Scaffolds, Collagen, Gelatin, Crosslinking
Publication Reference: https://www.repository.cam.ac.uk/handle/1810/249083
The authors would like to thank the British Heart Foundation (Grants NH/11/1/28922 and RG/09/003/27122) and the ERC Advanced Grant 320598 3D-E for providing financial support for this project. D. V. Bax is funded by the Peoples Programme of the EU 7th Framework Programme (RAE no: PIIF-GA-2013-624904) and also supported by an EPSRC IKC Proof of Concept Award.
British Heart Foundation (NH/11/1/28922)
British Heart Foundation (RG/09/003/27122)
European Research Council (320598)
EPSRC (via University of Leeds) (unknown)
External DOI: https://doi.org/10.1016/j.actbio.2015.07.034
This record's URL: https://www.repository.cam.ac.uk/handle/1810/249120
Attribution 2.0 UK: England & Wales
Licence URL: http://creativecommons.org/licenses/by/2.0/uk/