Visible-Light-Curable Catechol-Reinforced Gelatin Bioglue for Rapid Hemostasis and Engineered Tissue Assembly

Hydrogel-based tissue adhesives hold promise for diverse biomedical applications, yet achieving strong, durable adhesion to wet, dynamic biological surfaces remains challenging. The catechol-containing amino acid 3,4-dihydroxy-l-phenylalanine (DOPA) is a crucial functional motif in mussel-inspired adhesives and has been extensively investigated for incorporation into various biomaterials. However, conventional approaches of DOPA incorporation and subsequent crosslinking have shown limited potential for clinical translation. We developed a bioinspired strategy involving pH-controlled enzymatic conversion of tyrosine residues in porcine gelatin into DOPA. The resulting catechol-functionalized gelatin was blended with native tyrosine-rich gelatin to form a hybrid adhesive hydrogel, termed DOPA-tyrosine gelatin (DTG) bioglue. DTG was designed to achieve (a) rapid visible-light-driven ruthenium-based crosslinking for structural integrity and (b) enhanced interfacial adhesion via DOPA-mediated interactions with tissue surface. Its shear-thinning and fast-curing properties enable its use as a bioink for both extrusion-based and digital-light-processing 3-dimensional bioprinting. We demonstrated the DTG-assisted tissue-tissue integration for large-area construct assembly, addressing current volumetric fabrication limitations in microextrusion bioprinting. Moreover, it demonstrated superior hemostatic performance in rat liver and vascular injury models. Collectively, DTG bioglue is a promising candidate for next-generation adhesive biomaterial for regenerative medicine and surgical applications.