Catechol Derivative‐Based Bioadhesives: Molecular Design for Precision Medical Adhesion

ABSTRACT Acute tissue injuries demand bioadhesives with strong wet adhesion, biocompatibility, and mechanical adaptability. While mussel‐inspired catechol‐based adhesives hold promise, current designs often neglect the role of molecular diversity in tuning cohesion–adhesion dynamics. Inspired by the hierarchical branching of trees, where branch length and position determine fruit composition, we developed a structurally tunable bioadhesive platform by grafting five DOPA‐derived catechol derivatives—varying in side‐chain length and substituents—onto polyvinyl alcohol (PVA) via esterification. Computational, spectroscopic, structural, and mechanical analyses revealed that side‐chain length and substituents critically modulate the adhesive and cohesive properties of the hydrogels. Among these, the PVA‐CA system exhibited superior cohesion and adhesion across diverse substrates, attributed to the extended side chain and conjugated double bond of caffeic acid (CA) that enhance intramolecular packing and interfacial interactions. Ex vivo adhesion on porcine/canine cardiac, pulmonary, and intestinal tissues, along with in vivo studies in hepatic defect and skin wound models, confirmed strong adhesion, biocompatibility, and improved tissue regeneration of PVA‐CA hydrogel. This work establishes a programmable molecular design strategy for next‐generation wet‐tissue adhesives with broad biomedical potential.