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.

Automated summary

By oxidative oligomerization of catecholic compounds, gelatin can be functionalized with caffeic acid (CA) oligomers to enhance its bioadhesive properties. Ex vivo adhesion tests on pig lungs showed a 33-fold improvement in adhesion strength compared to gelatin methacryloyl controls, with increased toughness and stretchability. Functionalization with CA oligomers also allows for rapid gel formation at room temperature, adjustable viscosity for injectability, and enhanced antioxidant effects.