Preparation, mechanical properties and cytocompatibility of chemically crosslinked silk fibroin gradient hydrogel

Abstract To address the contradiction of ‘strong but brittle’ in traditional chemical cross-linked silk protein hydrogels, this paper proposes the GradEx-Cross strategy specifically involving the gradient concentration of glutaraldehyde (GTA) and the specific Schiff base cross-linking of tyrosine residues in silk protein. By distributing the GTA concentration from 3.0% at the core to 0.5% at the surface in a gradient pattern, a ‘hard core - soft shell’ heterogeneous network structure is constructed. This strategy utilizes the specific reaction between the phenolic hydroxyl groups of tyrosine residues and the aldehyde groups of glutaraldehyde to form stable covalent bonds, avoiding interference from multiple cross-linking agents and simultaneously optimizing the mechanical properties of the hydrogel. Experimental results show that the compressive strength of the prepared hydrogel reaches 0.85 ± 0.06 MPa, the elastic recovery rate after cyclic compression is >92%, and the β - folding content is increased by 42.8% compared to a uniform cross-linking system. This gradient cross-linking method provides a new path for the preparation of high-strength and high-elastic silk protein hydrogels, and has potential application value in cartilage repair and flexible biomaterials fields.