Promoting bone regeneration of calcium phosphate cement by addition of PLGA microspheres and zinc silicate via synergistic effect of in -situ pore generation, bioactive ion stimulation and macrophage immunomodulation

Calcium phosphate cement (CPC) is an excellent bone graft material due to its self -setting, easiness to shape, good biocompatibility and osteoconductivity. However, low osteogenic activity and slow degra- dation rate of CPC severely influence its bone regeneration efficiency. Herein, zinc silicate (ZS) and poly (lactic -co -glycolic acid) (PLGA) microspheres were incorporated into CPC to overcome these issues. The addition of ZS obviously downregulated the expression of inflammatory -related genes (interleukin-1?, interleukin-6, and tumor necrosis factor a), while markedly upregulated the anti-inflammatory gene expression (interleukin-10). The incorporation of ZS significantly promoted the adhesion and prolifer- ation of mouse bone marrow stem cells (mBMSCs). In addition, macrophage -conditioned ZS/PLGA/CPC extracts profoundly promoted osteogenic differentiation of mBMSCs, and evidently suppressed osteo- clastogenesis of RAW264.7 cells. The optimum added amount of ZS was 10 wt.%. In vivo results also displayed that the addition of 10 wt.% ZS significantly improved bone repair effect of the composite. Therefore, the addition of ZS together with PLGA microspheres is a promising way for modifying the osteogenic activity and degradability of CPC via in -situ pore generation, promoting osteogenic differen- tiation and macrophage immunomodulation due to the simultaneous release of active silicon and zinc ions. (C) 2020 Elsevier Ltd. All rights reserved.