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

Abstract 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 degradation 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-1β, interleukin-6, and tumor necrosis factor α), while markedly upregulated the anti-inflammatory gene expression (interleukin-10). The incorporation of ZS significantly promoted the adhesion and proliferation of mouse bone marrow stem cells (mBMSCs). In addition, macrophage-conditioned ZS/PLGA/CPC extracts profoundly promoted osteogenic differentiation of mBMSCs, and evidently suppressed osteoclastogenesis 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 differentiation and macrophage immunomodulation due to the simultaneous release of active silicon and zinc ions.