Injectable gelatin-oligo-catechol conjugates for tough thermosensitive bioadhesion

Extracellular matrix-derived biomaterials, such as gelatin-based hy-drogels, are attractive candidates for sealing internal leakages. However, gelatin derivatives are brittle and suffer from poor adhe-sion. Modifications of gelatin with adhesive catechol moieties have been limited to low degrees of substitution. Here, we propose oxidative oligomerization of catecholic compounds (namely, caf-feic acid [CA]) prior to the coupling reaction to augment the num-ber and availability of grafted catechol groups per carbodiimide conjugation reaction, thereby achieving robust bioadhesion. Ex vivo adhesion tests on pig lungs suggests -33 improvement in adhesion strength compared with gelatin methacryloyl controls due to their enhanced cohesion (i.e., X5.33 and X11.53 improve-ments in stretchability and toughness, respectively). Functionaliza-tion of gelatin with CA oligomers enables rapid formation of physical gels upon exposure to room temperature, tunes the vis-cosity of the gelatin-caffeic acid pre-gel solution for controllable injectability onto multiply curved tissues, and boosts the antioxi-dant effects of CA.