Silk Hydrogels Crosslinked by the Fenton Reaction

Abstract

Here, the Fenton reaction is used to prepare silk hydrogels through oxidation of tyrosine residues in silk fibroin, leading to dityrosine crosslinking. At pH 5.7, gelation occurs rapidly within 30 s, and the resultant opaque gels show soft properties with a storage modulus of ~100 Pa. The addition of ascorbic acid to the Fenton reaction increases the dityrosine bonds in the hydrogels but has little effect on the rheological or mechanical properties. The results indicate that Fe(III) ions significantly This article is protected by copyright. All rights reserved. 2 interacted with silk fibroin during the Fenton reaction, most likely binding to sites such as tyrosine, glutamate, and aspartate residues, triggering the formation of β-sheet structures that may impede dityrosine bond formation due to steric hindrance. The use of an iron chelator or the operation of the Fenton reaction at pH 9.2 enables control over the interaction of Fe(III) ions with silk fibroin, achieving a hydrogel with improved optical properties and enhanced dityrosine bond formation.Hydrogels prepared by the Fenton reaction are cytocompatible as L929 mouse fibroblasts remain viable and are proliferative when seeded on the hydrogels. The results offer a useful approach to generate chemically crosslinked silk fibroin hydrogels without the use of enzyme-catalyzed reactions for biomedical applications.

Rapid and cytocompatible cell-laden silk hydrogel formation via riboflavin-mediated crosslinking

“…Generally, the absorption bands at 1640-1655 cm À1 are associated with the random coils, while the bands at 1610-1630 cm À1 are indicative of a b-sheet conformation. [33][34][35] For all samples (Fig. S3, ESI †), the presence of absorption bands at 1640-1655 cm À1 was observed, which are associated to the random coils.…”

Photo-Crosslinked Silk Fibroin for 3D Printing

“…Furthermore, exogenous enzymes after crosslinking can be entrapped in the hydrogels, as the mesh size of the molecular networks is small, and this could have an adverse impact on cells and elicits a harmful immune response unless human-derived peroxidase is used [ 45 ]. The Fenton reaction is another option to covalently crosslink silk fibroin via dityrosine bonds and is promising for 3D printing [ 46 , 47 ].…”

Silk Biomaterials for Bone Tissue Engineering

“…[ 86–88 ] Unlike tough native silk fibers, most of the regenerated silk materials are weak and brittle due to the loss of compact hydrogen bonding at the inter‐molecular level. [ 89 ] Different modification strategies such as enzyme crosslinking, [ 90 ] physical crosslinking, [ 91 ] and biomineralization [ 92 ] were developed to optimize the preparation process of silk biomaterials with better hierarchical structures and crystalline compositions. Strong demand remains to improve the mechanical strength of the regenerated silk materials used in BTE.…”