<b>Suckerin Colloids and Hydrogels with Low Immunogenicity as Resorbable and Hemostatic Tissue Adhesives for Wound Healing</b>

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 <i>vivo</i> 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 <i>in vivo </i>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.