3D-Printable, Self-Stiffening (4D) and Shape Morphing Hydrogel through Single-Step Orthogonal Crosslinking of Phenolic Biopolymers for Dynamic Tissue Engineering

This study presents a multicomponent hydrogel composed of silk fibroin (SF), tyramine-modified hyaluronic acid (HA_Tyr), and tyramine-modified gelatin (G_Tyr) that undergoes enzymatic orthogonal crosslinking via phenolic group interactions. The resulting SHG hydrogel demonstrates self-stiffening and shape-morphing properties (4D behavior) when exposed to physiological conditions (37 °C, PBS), due to SF conformational folding and fibril formation. The extrusion-based 3D-printable hydrogel allows precise geometrical fabrication, and exhibits tunable mechanical properties, excellent biocompatibility, and proangiogenic behavior in the CAM assay, making it a strong candidate for dynamic and fibrillar tissue regeneration.