PLGA/BGP/Nef Porous Composite Restrains Osteoclasts by Inhibiting the NF-κB Pathway, Enhances IGF-1-mediated Osteogenic Differentiation and Promotes Bone Regeneration

BackgroundNovel bone substitutes are urgently needed in experimental research and clinical orthopaedic applications. There are many traditional Chinese medicines that have effects on bone repair. However, application of natural medicines in traditional Chinese medicine to bone tissue engineering and its mechanism were rarely reported.ResultsIn this study, the osteogenic ability of bioactive glass particles (BGPs) and the osteogenic and osteoclastic ability of neferine (Nef) were fused into PLGA-based bone tissue engineering materials for bone regeneration. BGPs were prepared by spray drying and calcination. Particles and Nef were then mixed with PLGA solution to prepare porous composites by the phase conversion method. Here we showed that Nef inhibited proliferation and enhanced ALP activity of MC3T3-E1 cells in a dose- and time-dependent manner. And the composites containing Nef could also inhibit RANKL-induced osteoclast formation (p < 0.05). Mechanistically, the PLGA/BGP/Nef composite downregulated the expression of NFATC1 by inhibiting the NF-& kappa;B pathway to restrain osteoclasts. In the other hands, PLGA/BGP/Nef composite was first demonstrated to effectively activate the IGF-1R/PI3K/AKT/mTOR pathway to enhance IGF-1-mediated osteogenic differentiation. The results of animal experiments show that the material can effectively promote the formation and maturation of new bone in the skull defect site.ConclusionsThe PLGA/BGP/Nef porous composite can restrain osteoclasts by inhibiting the NF-& kappa;B pathway, enhance IGF-1-mediated osteogenic differentiation and promotes bone regeneration, and has the potential for clinical application.