Supramolecular Cross-Links in Mussel-Inspired Tissue Adhesives

Here we introduce a tissue-adhesive patch with orthogonal cohesive and adhesive chemistries; supramolecular ureido-4-pyrimidinone (UPy) cross-links provide cohesive strength, and catechols provide mussel-inspired tissue adhesion. In the development of tissue-adhesive biomaterials, prior research has focused on forming strong adhesive interfaces in wet conditions, leaving the use of supramolecular cross-links for cohesive strength underexplored. In developing this adhesive patch, the influence of the comonomers' composition and amphiphilicity on adhesion was investigated by lap shear adhesion to wet tissue. We determined failed lap joints' failure mechanism using catechol-specific Arnow's stain and identified formulations with improved cohesive strength. The adhesive materials were cytocompatible in mammalian cell conditioned media viability studies. We found that using orthogonal motifs to independently control adhesives' cohesive and adhesive strengths resulted in stronger tissue adhesion. The design principles presented here advance the development of wet tissue adhesives and could allow for the future design of biomaterials with desirable stimuli-responsive properties.