Silk Fibroin/GelMA-Based Hydrogels as a Platform for Tissue Adhesives and Tissue Engineering

Silk fibroin (SF) and gelatin methacryloyl (GelMA)-based hydrogels are emerging as promising biomaterials for various biomedical applications due to their unique physiological and physicochemical properties. This Review highlights the synergistic advantages of SF/GelMA hydrogels, focusing on their physicochemical tunability, biocompatibility, and multifunctionality. SF contributes to structural integrity and mechanical strength through the formation of crystalline β-sheet domains, while GelMA provides a photo-cross-linkable functionality, facilitating precise modulation of mechanical and structural properties beneficial for cell support. Various cross-linking strategies, including physical (ionic, hydrogen bonding, hydrophobic interaction, and crystalline formation) and chemical (covalent cross-linking, photo-cross-linking, and enzymatic), are explored to optimize SF/GelMA hydrogels for enhanced tissue adhesion and tissue (skin, muscle, cartilage, bone, tendon, and ligament) regeneration applications. Furthermore, we address the current key translational challenges such as long-term biostability, large-scale production, and immune-regulatory pathways for successful clinical implementation for applications in regenerative medicine, including tissue repair and tissue reconstruction.