Self-healing injectable hydrogels with moist adhesion and osteogenic activity for bone tissue regeneration

Critical-sized bone defects caused by trauma, tumor resection, and congenital disorders remain a major clinical challenge in orthopedic and craniofacial surgery, and injectable self-healing hydrogels offer attractive advantages for bone repair owing to their minimally invasive delivery, adaptability to irregular defect geometries, and dynamic structural properties. In this study, an injectable self-healing hydrogel was developed by combining phenylboronic acid–modified hyaluronic acid (HA-PBA) with amine-functionalized poly(ethylene glycol diglycidyl ether) (p-EGDE), forming a dynamic network through synergistic boronic ester bonding and boron–nitrogen coordination. The gelation behavior, rheological properties, self-healing ability, wet adhesion, degradation profile, and cytocompatibility were systematically evaluated in vitro , and the osteogenic performance and systemic biosafety were further assessed in a rat critical-sized calvarial defect model. The resulting hydrogels exhibited rapid gelation, pronounced shear-thinning behavior, autonomous self-healing, tunable wet adhesion, and controllable degradation. In vitro CCK-8 assays demonstrated that the hydrogels and their precursor components exhibited no significant cytotoxicity toward bone marrow mesenchymal stem cells, with cell viability exceeding 90% at all tested concentrations (2–32 mg/mL) and time points (24–72 h). In vivo evaluation showed that HA-PBA/p-EGDE hydrogels significantly promoted bone regeneration compared with the control group, while histological analysis of major organs confirmed good systemic biosafety. These results indicate that HA-PBA/p-EGDE hydrogels represent a promising injectable scaffold for bone defect repair.