Efficient catechol functionalization of biopolymeric hydrogels for effective multiscale bioadhesion

Hydrogels are promising soft materials for the delivery of therapeutic cells and cargo molecules. Inspired by mussel adhesion chemistry, hydrogels based on catechol (Cat)-modified polysaccharides have been developed to enhance hydrogel-tissue interactions. However, due to the inevitable side reactions such as self-polymerization of dopamine involved in the conventional catechol conjugation process, the efficiency of catechol conjugation to polymers is typically low, leading to insufficient stability, low mechanical strength, and poor adhesiveness of these catechol-modified hydrogels. In this study, we report a new approach to synthesize catechol-functionalized hyaluronic acid with improved degree of substitution. Due to the significantly increased conjugated Cat groups, the obtained HA-Cat hydrogels not only can adhere to tissue samples under wet conditions but also can capture cell adhesion proteins to enhance cell attachment and spreading. Meanwhile, owing to the extensive Cat-protein interactions, these hydrogels can also facilitate long-term release of protein-based therapeutic cargoes, such as the osteoinductive BMP-2 protein, thereby effectively promoting osteogenic differentiation of stem cells. These findings show that the HA-Cat hydrogels are ideal carriers of therapeutic cells and drugs for tissue regeneration.