Engineering injectable bone/bioadhesive grafts delivery system with self-healing properties for bone regeneration

The incidence of open bone defects caused by high kinetic and potential energy injuries has significantly increased. Bone grafting, typically in the form of granules, is widely recognized as the most effective treatment. However, current bone graft system is not considered ideal due to issues such as mismatched shapes and dislocation. Additionally, bone defects are frequently associated with substantial bleeding, and bone graft system often fail to effectively seal and prevent leakage, increasing the post-operative complications. In this study, based on PEG active ester (Bi-PEG-SG) and gelatin, we developed a micro-scale calf bone granules/PEG-Gelatin bioadhesive grafts delivery system with self-healing properties, which not only possesses antioxidant properties but also demonstrates injectability, shape adaptability, adhesive capabilities and high bursting pressure. This system effectively addresses the displacement issues of bone grafts and shows significant sealing and hemostatic capabilities in models of femoral artery transection hemorrhage and rabbit femoral condyle bleeding. Furthermore, the bone/bioadhesive graft delivery system serves as a sustained-release carrier for vancomycin and recombinant human bone morphogenetic protein-2, demonstrating good antibacterial performance and enhancing the osteoinductive activity and osteogenic microenvironment of calf bone granules, thereby promoting the repair of bone defects. Overall, this system offers a promising alternative for the fabrication of bone granules delivery system, demonstrating significant potential as a treatment option for open bone defects.