Conformational Transition‐Driven Self‐Folding Hydrogel Based on Silk Fibroin and Gelatin for Tissue Engineering Applications

Self-folding is a rapidly evolving method for converting flat objects into three-dimensional (3D) structures. However, because there are few materials with suitable properties, the application of self-folding in tissue engineering has been hindered greatly. Herein, a novel self-folding hydrogel using conformational transition mechanism is developed by employing photocrosslinkable silk fibroin and gelatin composite hydrogel. It is hypothesized that differences in the amount of beta-sheet (β-sheet) formation between the upper and lower layers will supply additional folding stress and drive the self-folding behavior of a bilayer patch, which can improve the mechanical properties and long-term stability of the self-folded structure. In this study, the impact of various proportions of β-sheets in composite hydrogels on their swelling, mechanics, and internal microstructures are investigated. Subsequently, the folding process parameters are optimized, and diffusion through the folded tubular structure is studied with a perfusion test. Finally, it is proven that the self-folding hydrogel system is cytocompatible and can be utilized to build a 3D coculture system of "endothelial cells-smooth muscle cells". These findings suggest that the self-folding hydrogel can be a promising candidate for applications in blood vessel tissue engineering and regenerative medicine.