Dopamine-Modified Hyaluronic Acid Hydrogel Adhesives with Fast-Forming and High Tissue Adhesion

Commercial or clinical tissue adhesives are currently limited due to their weak bonding strength on wet biological tissue surface, low biological compatibility, and slow adhesion formation. Although catechol-modified hyaluronic acid (HA) adhesives are developed, they suffer from limitations: insufficient adhesiveness and overfast degradation, attributed to low substitution of catechol groups. In this study, we demonstrate a simple and efficient strategy to prepare mussel-inspired HA hydrogel adhesives with improved degree of substitution of catechol groups. Because of the significantly increased grafting ratio of catechol groups, dopamine-conjugated dialdehyde–HA (DAHA) hydrogels exhibit excellent tissue adhesion performance (i.e., adhesive strength of 90.0 ± 6.7 kPa), which are significantly higher than those found in dopamine-conjugated HA hydrogels (∼10 kPa), photo-cross-linkable HA hydrogels (∼13 kPa), or commercially available fibrin glues (2–40 kPa). At the same time, their maximum adhesion energy is 384.6 ± 26.0 J m–2, which also is 40–400-fold, 2–40-fold, and ∼8-fold higher than those of the mussel-based adhesive, cyanoacrylate, and fibrin glues, respectively. Moreover, the hydrogels can gel rapidly within 60 s and have a tunable degradation suitable for tissue regeneration. Together with their cytocompatibility and good cell adhesion, they are promising materials as new biological adhesives.