Manipulating Mg/Ca ratios in MgO-CaO-SiO2 bioactive glass for achieving accelerated osteogenic differentiation of human adipose-derived stem cells

Abstract

Cell-containing biomaterial is a promising material for treating nonunion or critical bone defect. Human adipose-derived stem cells (hADSCs) are suitable for bone repair due to their abundance in the abdomen, thighs, and buttocks. However, the low osteogenic capacities of hADSCs hinder their extended development for bone regeneration application. The present goal explores a novel MgO-CaO-SiO₂ bioactive glass with suitable Mg/Ca ratios to enhance the osteogenic differentiation and bioactivity of hADSCs. The synthetic bioglass can be expressed as xMgO-(2-x)CaO-SiO₂ (abbreviated as Mg_(x)Ca_(2-x)Si₂, x = 0, 0.25, 0.5, 0.75, and 1). The expression levels of osteoblast-related genes (i.e., BMP2, RUNX2, DLX5, COL1A1, BGLAP2, and SPP1) were evaluated by reverse transcription-quantitative PCR (RT-PCR). The proteins involved in the p38/Akt/ERK signaling pathways were analyzed with Western blots. The results indicated that the extractions from the Mg_(x)Ca_(2-x)Si₂ bioglass promoted hADSCs proliferation. Among the Mg_(x)Ca_(2-x)Si₂ bioglass with different Mg/Ca ratios, the bioglass with a low Mg/Ca ratio (x = 0.25) presented greater osteogenic differentiation of hADSCs by promoting the p38 signaling pathway. Interestingly, the bioglass with low Mg/Ca ratio (x = 0.25) further presented on osteogenic potential with greater osteointegration in rat femoral defect model. This work provides the optimal Mg/Ca ratio in Mg_(x)Ca_(2-x)Si₂ bioglass to promote the osteogenic induction of hADSCs and bone regeneration.

Keywords: Bone engineering; Human adipose-derived stem cells; MgO-CaO-SiO(2) bioactive glass; Osteogenesis.