Enhanced osteogenesis, angiogenesis and inhibited osteoclastogenesis of a calcium phosphate cement incorporated with strontium doped calcium silicate bioceramic

Abstract

Biologically active ions doped calcium phosphates to stimulate osteogenesis, angiogenesis and suppress osteoclastogenesis is a promising strategy for accelerating osteoporotic bone repair. Among them, silicon (Si) and strontium (Sr) ions are beneficial for new bone and vessel regeneration. In this study, Si and Sr were jointly introduced into calcium phosphate cement (CPC) by incorporating strontium doped calcium silicate (Sr-CS) to stimulate osteoporotic bone repair. Sr-CS prolonged the setting time of CPC, but hardly altered the compressive strength and injectability. More thin-lamellar and cluster-like apatite crystals were formed on the surface of Si and Sr co-doped CPC during in vitro mineralization. Besides, CPC with Sr-CS could controllably and sustainedly release Ca, Si and Sr ions. The cell experiments showed 10Sr-CS/CPC and 20Sr-CS/CPC (10 and 20 mol.% doping content of Sr in Sr-CS, respectively) significantly promoted the proliferation, ALP activity, osteogenesis-related genes (ALP, Runx2, Col-I and OC) and proteins (Col I and OC) expression of mBMSCs. The extracts of 10Sr-CS/CPC and 20Sr-CS/CPC also effectively enhanced the angiogenesis-related gene (eNOs) of human umbilical vein endothelial cells (HUVECs) and more interconnected circles formed when the 20Sr-CS/CPC extract was added. Furthermore, the release of Si and Sr ions from 20Sr-CS/CPC extract suppressed the TRAP activity and the expression of osteoclastogenesis-related genes (TRAP and MMP9) in RAW264.7 cells. These results together indicate 20Sr-CS/CPC with enhanced osteogenesis and angiogenesis, proper setting properties and suppressed osteoclastogenesis has a great potential for stimulating osteoporotic bone regeneration.