Suckerin Colloids and Hydrogels With Low Immunogenicity as Resorbable and Hemostatic Tissue Adhesives for Wound Healing

ABSTRACT Squid sucker ring teeth proteins (suckerins) have recently been shown to exhibit higher molecular‐level adhesion than mussel adhesive proteins–a well‐known class of wet‐resistant adhesive proteins–and can also assemble into nanoparticles in aqueous conditions. Herein, we present recombinant suckerin‐12 colloids and hydrogels as bioadhesives with strong wet adhesion and excellent in vivo biocompatibility. These colloids and hydrogels displayed low cytotoxicity, minimal immunogenicity, and negligible hemolysis, while outperforming fibrin glue in hemostasis, skin cell proliferation and migration, wound closure, and healing. Suckerin hydrogels formulated via riboflavin‐mediated di‐tyrosine crosslinking preserved β‐sheet content and elasticity at an optimal crosslinking density, resulting in enhanced adhesion, hemocompatibility, and in vivo wound closure. Transcriptomic analysis further revealed regulation of genes associated with hemostasis, angiogenesis, proliferation, and re‐epithelialization, with minimal immune activation. Together, these findings establish suckerin‐based adhesives as promising next‐generation biomedical materials that combine scalability, stability under oxidative conditions, and superior performance for external wound repair.