Biodegradable dual-crosslinked adhesive glue for fixation and promotion of osteogenesis

Abstract The effective fixation of fracture fragments is the foundation for the smooth healing process of fracture. Due to the presence of small fracture fragments, the comminuted fracture cannot be fixed under high mechanical strength leading to the bone nonunion and delayed healing. In this study, the primary crosslinked injectable bone glue was fabricated by the Schiff base reaction between low substitution degree methacrylate gelatin (GelMa) and Oxidized dextran (oDex) covalently crosslinked with Aminated mesoporous bioactive glass nanoparticles (AMBGN), then the second crosslinked bone glue was formed among small fracture fragments after the irradiation. By this method, the osteogenic dual-crosslinking biodegradable bone glue was synthesized with enhanced mechanical capability. This bone glue was biocompatible and biodegradable, in addition, after the second crosslinking, the mechanical strength was 2.1 times higher than that in primary cross-linking. Moreover, the dual-crosslinked bone glue also exhibited excellent adhesion ability on the isolated rat bone tissues. Additionally, the bone glue can increase the proliferation of bone marrow mesenchymal stem cells (BMSCs) and enhance the expression of Alkaline phosphatase (ALP) and the deposition of calcium nodules with the up-regulating expression of the osteogenic protein (Runx2) and adhesin (Vinculin) in vitro. Furthermore, the bone glue also presented enhanced osteogenesis in the rat calvarial critical-size defect models in vivo. Overall, this osteogenic dual-crosslinking biodegradable bone glue with high mechanical strength provided a new approach in treating the comminuted fracture fragments.