Mussel-Inspired Injectable Hydrogel Adhesive Formed under Mild Conditions Features Near-Native Tissue Properties

Injectable hydrogel adhesives, especially those that can strongly adhere to tissues and feature near-native tissue mechanical properties, are desirable biomaterials for tissue repair. Compared to nonadhesive injectable hydrogels for minimally invasive delivery of therapeutic agents, they can better retain the delivered agents at targeted tissue locations and provide additional local physical barriers. However, regardless of recent advances, an ideal injectable hydrogel adhesive with both proper adhesion and mechanical matching between hydrogels and tissues is yet to be demonstrated with cytocompatible and efficient in situ curing methods. Inspired by marine mussels, where different mussel foot proteins (Mfps) function cooperatively to achieve excellent wet adhesion, we herein report a dual-mode-mimicking strategy by modifying gelatin (Gel) biopolymers with a single-type thiourea-catechol (TU-Cat) functionality to mimic two types of Mfps and their mode of action. This strategy features a minor, yet impactful modification of biopolymers, which gives access to collective properties of an ideal injectable hydrogel adhesive. Specifically, with TU-Cat functionalization of only ∼0.4-1.2 mol % of total amino acid residues, the Mfp-mimetic gelatin biopolymer (Gel-TU-Cat) can be injected and cured rapidly under mild and cytocompatible conditions, giving rise to tissue adhesive hydrogels with excellent matrix ductility, proper wet adhesion, and native tissue-like stress relaxation behaviors. Such a set of properties originating from our novel dual-mode-mimicking strategy makes the injectable hydrogel adhesive a promising platform for cell delivery and tissue repair.