The diazirine-mediated photo-crosslinking of collagen improves biomaterial mechanical properties and cellular interactions.

Autor: Ziverec A; Laboratory of Tissue Biology and Therapeutic Engineering, CNRS UMR 5305, University Claude Bernard-Lyon 1 and University of Lyon, 7 Passage du Vercors, 69367 Lyon Cedex 07, France., Bax D; Department of Materials Science and Metallurgy, University of Cambridge, 27 Charles Babbage Rd, Cambridge CB3 0FS, United Kingdom., Cameron R; Department of Materials Science and Metallurgy, University of Cambridge, 27 Charles Babbage Rd, Cambridge CB3 0FS, United Kingdom., Best S; Department of Materials Science and Metallurgy, University of Cambridge, 27 Charles Babbage Rd, Cambridge CB3 0FS, United Kingdom., Pasdeloup M; Laboratory of Tissue Biology and Therapeutic Engineering, CNRS UMR 5305, University Claude Bernard-Lyon 1 and University of Lyon, 7 Passage du Vercors, 69367 Lyon Cedex 07, France., Courtial EJ; 3dFAB, Univ Lyon, Université Lyon1, CNRS, INSA, CPE-Lyon, ICBMS, UMR 5246, 43, Bd du 11 novembre 1918, 69622 Villeurbanne, France., Mallein-Gerin F; Laboratory of Tissue Biology and Therapeutic Engineering, CNRS UMR 5305, University Claude Bernard-Lyon 1 and University of Lyon, 7 Passage du Vercors, 69367 Lyon Cedex 07, France., Malcor JD; Laboratory of Tissue Biology and Therapeutic Engineering, CNRS UMR 5305, University Claude Bernard-Lyon 1 and University of Lyon, 7 Passage du Vercors, 69367 Lyon Cedex 07, France. Electronic address: jean-daniel.malcor@ibcp.fr.
Jazyk: angličtina
Zdroj: Acta biomaterialia [Acta Biomater] 2024 May; Vol. 180, pp. 230-243. Date of Electronic Publication: 2024 Apr 02.
DOI: 10.1016/j.actbio.2024.03.033
Abstrakt: In tissue engineering, crosslinking with carbodiimides such as EDC is omnipresent to improve the mechanical properties of biomaterials. However, in collagen biomaterials, EDC reacts with glutamate or aspartate residues, inactivating the binding sites for cellular receptors and rendering collagen inert to many cell types. In this work, we have developed a crosslinking method that ameliorates the rigidity, stability, and degradation rate of collagen biomaterials, whilst retaining key interactions between cells and the native collagen sequence. Our approach relies on the UV-triggered reaction of diazirine groups grafted on lysines, leaving critical amino acid residues intact. Notably, GxxGER recognition motifs for collagen-binding integrins, ablated by EDC crosslinking, were left unreacted, enabling cell attachment, spreading, and colonization on films and porous scaffolds. In addition, our procedure conserves the architecture of biomaterials, improves their resistance to collagenase and cellular contraction, and yields material stiffness akin to that obtained with EDC. Importantly, diazirine-crosslinked collagen can host mesenchymal stem cells, highlighting its strong potential as a substrate for tissue repair. We have therefore established a new crosslinking strategy to modulate the mechanical features of collagen porous scaffolds without altering its biological properties, thereby offering an advantageous alternative to carbodiimide treatment. STATEMENT OF SIGNIFICANCE: This article describes an approach to improve the mechanical properties of collagen porous scaffolds, without impacting collagen's natural interactions with cells. This is significant because collagen crosslinking is overwhelmingly performed using carbodiimides, which results in a critical loss of cellular affinity. By contrast, our method leaves key cellular binding sites in the collagen sequence intact, enabling cell-biomaterial interactions. It relies on the fast, UV-triggered reaction of diazirine with collagen, and does not produce toxic by-products. It also supports the culture of mesenchymal stem cells, a pivotal cell type in a wide range of tissue repair applications. Overall, our approach offers an attractive option for the crosslinking of collagen, a prominent material in the growing field of tissue engineering.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: