Improved osteogenesis and angiogenesis of magnesium-doped calcium phosphate cement viamacrophage immunomodulationElectronic supplementary information (ESI) available: XRD analysis of magnesium–calcium phosphate cement samples. Isotype control data of flow cytometry. ALP activity of BMSCs and sprouting analysis of HUVECs in transwell co-culture system. See DOI: 10.1039/c6bm00290k

Immune responses are vital for bone regeneration and play an essential role in the fate of biomaterials after implantation. As a kind of plastic cell, macrophages are central regulators of the immune response during the infection and wound healing process including osteogenesis and angiogenesis. Magnesium–calcium phosphate cement (MCPC) has been reported as a promising candidate for bone repair with promoted osteogenesis both in vitroand in vivo. However, relatively little is known about the effects of MCPC on immune response and the following outcome. In this study, we investigated the interactions between macrophages and MCPC. Here we found that the pro-inflammatory cytokines including TNF-α and IL-6 were less expressed and the bone repair related cytokine of TGF-β1 was up-regulated by macrophages in MCPC extract. Furthermore, the enhanced osteogenic capacity of BMSCs and angiogenic potential of HUVECs were acquired in vitroby the MCPC-induced immune microenvironment. These findings suggest that MCPC is able to facilitate bone healing by endowing favorable osteoimmunomodulatory properties and influencing crosstalk behavior between immune cells and osteogenesis-related cells.