Preparation of mussel-inspired injectable hydrogels based on dual-functionalized alginate with improved adhesive, self-healing, and mechanical properties

Injectable hydrogels have aroused much attention for the advantages such as minimally invasive surgery, avoidance of surgical trauma, and filling and repairing irregularly shaped tissue defects. Mussel-inspired injectable hydrogels can be immobilized on the surface of tissues, resulting in stable biomaterial-tissue integration. However, the commonly used biomimetic mussel-inspired hydrogels are prepared by the oxidation of catechol groups, which involves the introduction or production of cytotoxic substances. Moreover, mussel-inspired hydrogels generally display weak mechanical strength and poor adhesiveness because of the consumption of catechol groups during oxidation. Herein, we described a strategy to prepare mussel-inspired injectable hydrogels via the Schiff base reaction. We grafted dopamine, an adhesive motif discovered in the holdfast pads of mussels, to aldehyde-modified alginate backbones. A series of injectable mussel-inspired adhesive, self-healing hydrogels were fabricated by in situ crosslinking of hydrazide-modified poly(l-glutamic acid) (PLGA-ADH) and dual-functionalized alginate (catechol- and aldehyde-modified alginate, ALG-CHO-Catechol). Also, oxidized ALG-CHO-Catechol hydrogels and PLGA/ALG-CHO hydrogels were prepared for comparison. The effects of the crosslinking method, catechol grafting ratio and solid content on the mechanical properties, self-healing behavior, adhesive properties, and hemostatic ability were investigated. Compared with the observations for oxidized ALG-CHO-Catechol hydrogels, more reasonable gelation time and notably enhanced mechanical properties and adhesive behavior were detected in the PLGA/ALG-CHO-Catechol hydrogel system. The PLGA/ALG-CHO-Catechol hydrogels also displayed clear self-healing ability and good cytocompatibility. The strong bioadhesion endowed the PLGA/ALG-CHO-Catechol hydrogels with superior hemostatic performance. These results suggested that PLGA/ALG-CHO-Catechol hydrogel might have great potential as an antibleeding and tissue repair material.