Enhanced bone regeneration with BMP-2 loaded functional nanoparticle–hydrogel complex

As an efficient sustained release system of BMP-2, a functional nanoparticle–hydrogel complex, composed of heparin-functionalized nanoparticles and fibrin gel, was developed and used as a bone graft. In vivo bone formation was evaluated by soft X-ray, histology, alkaline phosphatase (ALP) activity, immunostaining, and mineral content analysis, based on the rat calvarial critical size defect model. Significantly improved and effective bone regeneration was achieved with the recombinant BMP-2 (4 μg) loaded nanoparticle–fibrin gel complex, as compared to bare fibrin gel, the nanoparticle–fibrin gel complex without BMP-2, or even the BMP-2 loaded fibrin gel. These improvements included areas such as radiodensity, the bone-specific ALP activity, the osteocalcin immunoreactivity, and the ratios of calcium and phosphate contents with respect to normal bone in the regenerated bone area. The remodeling process of new bone developed with BMP-2 was significantly enhanced, and more mature and highly-mineralized bone was obtained by utilizing the functional nanoparticle–hydrogel complex. These results indicate that the nanoparticle–fibrin gel complex can be a promising candidate for a new bone defect replacement matrix, and an enhanced BMP-2 carrier.