Synthesis of Entirely Protein-Based Hydrogels by Enzymatic Oxidation Enabling Water-Resistant Bioadhesion and Stem Cell Encapsulation

Growing complexity in modern surgery and guided tissue repair calls for new materials capable of dual functions—water-resistant adhesion to biological tissues and stem cell encapsulation/delivery. Here, we demonstrate the creation of entirely recombinant protein-based adhesive hydrogels by leveraging the sequence derived from natural adhesive molecules—mussel foot protein-3 (Mfp-3), in vitro enzymatic oxidation mediated by recombinant tyrosinase and genetically encoded SpyTag/SpyCatcher chemistry. The resulting materials exhibited varied stiffness dependent on the polymer concentration, strong water-resistant adhesion to porcine skin, and excellent compatibility with 3D stem cell culture. The presence of SpyCatcher domains within the protein networks also enabled postgelation decoration with SpyTagged proteins under mild physiological conditions. These results point to a new approach for designing genetically programmable materials that enable both water-resistant bioadhesion and stem cell encapsulation f...