In vitro and in vivo study of concentrated growth factor (CGF) mediating macrophage polarization in bone defect repair

Abstract

Concentrated growth factor (CGF) is widely applied in clinical practice, but whether it has bone promoting effects and its mechanism of action are still the focus of discussion. In this study, in vitro experiments demonstrate that CGF can promote the expression of Arg-1 in BMDM cells, facilitating their polarization towards the M2 macrophages and encouraging the secretion of IL-10 and VEGF-A. CGF modulates M1 macrophages by reducing the expression of iNOS, while enhancing Arg-1 expression, thereby converting them to M2 macrophages. This is accompanied by a decrease in the secretion of TNF-$\alpha$ and IL-1β, and an increase in the secretion of IL-10 and VEGF-A. Mechanistically, CGF promotes the phosphorylation of STAT3, which in turn induces M2 macrophage polarization, suggesting that the function of CGF-mediated macrophages may be associated with the STAT3 signaling pathway. Moreover, CGF-mediated macrophages were found to enhance osteoblast activity, increasing the expression of ALP, RUNX2, and BMP-2, and improving cell migration capabilities. In vivo experiments showed that CGF could early recruit M2 macrophages to the bone defect site, promoting the expression of bone formation-related proteins such as ALP and BMP-2, and accelerating bone tissue regeneration. In summary, our study demonstrates that CGF can induce bone repair and regeneration by promoting immune modulation and macrophage polarization.