Combined study on the action and mechanism of G-Rg1/Sr-CaS bone substitute material for ossification and pro-vascularization

Abstract

Neovascularization is important for bone repair, vascularization, and ossification during bone repair. Ginsenoside Rg1 (G-Rg1), which is the main extract of ginseng, has been shown to promote therapeutic angiogenesis. It has been studied in the field of biomaterials, but there is no relevant report in the field of bone substitute materials. In this study, we successfully prepared the bone substitute material combining calcium sulphate (Sr-CaS) with G-Rg1 on the basis of previous research work. In vitro experiments were carried out to verify the ossification of composites by using mouse bone marrow mesenchymal stem cells (BMMSCs) and the ossification was quantified by western blot. The related proteins in the key signaling pathways for the different concentrations of G-Rg1/Sr-CaS composite extract were studied to determine whether there was receptor competition and to find the optimal ratio parameters. The vascularization of the composite was verified in the human umbilical vein endothelial cells (HUVECs) model, and finally the coordination of pro-vascularization and ossification was evaluated in the mouse critical bone defect model. The results indicated that G-Rg1/Sr-CaS composites contributed to ossification in the mouse BMMSC model and vascularization in the HUVEC model. The G-Rg1/Sr-CaS composites resulted in significantly greater bone mineral densities and bone volume/total volume of the defect group compared to the control group. Histological analysis showed that the G-Rg1/SrCaS was resorbable with satisfactory biocompatibility. The doped strontium ions enhanced the bone repair performance of G-Rg1/Sr-CaS in the mouse model and the new substitute demonstrated promising results for clinical use.