Photo-Cross-Linking Approach to Engineering Small Tyrosine-Containing Peptide Hydrogels with Enhanced Mechanical Stability

Peptide-based supramolecular hydrogels have been extensively explored in biomaterials owing to their unique bioactive, stimulus-responsive, and biocompatible features. However, peptide-based hydrogels often have low mechanical stability with storage moduli of 10-1000 Pa. They are susceptible to mechanical destruction and solvent erosion, greatly hindering their practical application. Here, we present a photo-cross-linking strategy to enhance the mechanical stability of a peptide-based hydrogel by 10(4)-fold with a storage modulus of ~100 kPa, which is one of the highest reported so far for hydrogels made of small peptide molecules. This method is based on the ruthenium-complex-catalyzed conversion of tyrosine to dityrosine upon light irradiation. The reinforcement of the hydrogel through photo-cross-linking can be achieved within 2 min thanks to the fast reaction kinetics. The enhancement of the mechanical stability was due to the formation of a densely entangled fibrous network of peptide dimers through a dityrosine linkage. We showed that in order to implement this method successfully, the peptide sequence should be rationally designed to avoid the cross talk between self-assembly and cross-linking. This method is convenient and versatile for the enhancement of the mechanical stability of tyrosine-containing peptide-based hydrogels. We anticipate that the photo-cross-linked supramolecular hydrogels with much improved mechanical stability will find broad applications in tissue engineering and drug controlled release.