Local delivery of naringin in beta-cyclodextrin modified mesoporous bioactive glass promotes bone regeneration: from anti-inflammatory to synergistic osteogenesis and osteoclastogenesis

Abstract

The bone immune response dominated by macrophages plays an indispensable role in the osteogenesis of bone defects. Moreover, moderate polarization of macrophages against inflammatory M2 has been proved to promote osteogenesis. Therefore, the addition of anti-inflammatory agents to bioactive bone repair materials facilitates efficient bone regeneration by regulating the polarization of macrophages. Bioactive glass (BG) has been widely used for bone defect repair. However, BG alone cannot effectively inhibit the inflammatory response caused by in vivo biomaterial implantation, and finally cannot achieve satisfactory bone repair effect. Herein, the design of mesoporous bioactive glass nanoparticles (MBG) modified with β-cyclodextrin (CD-MBG) is reported. Our research shows that the anti-inflammatory drug naringin (NG) is loaded into CD-MBG (NG@CD-MBG), which achieves a sustained release within 6 days. In vitro studies reveal that NG@CD-MBG promotes better transformation of macrophages to the M2 phenotype than MBG inhibiting macrophage inflammatory responses, while the induced local immune microenvironment synergistically facilitates osteogenesis and inhibits osteoclastogenesis. Furthermore, in vivo high expression of osteogenesis-related genes in the microenvironment stimulated by NG@CD-MBG significantly promotes new bone formation in the femoral defect model of rats. The results indicate that the combination of MBG and NG has a synergistic effect on immunomodulating osteogenesis and osteoclastogenesis, providing a novel idea for the development of bone biomaterials with favorable bone immunomodulatory properties.