The role of CaO/SiO2 ratio and P2O5 content in gel-derived bioactive glass-polymer composites in the modulation of their bioactivity and osteoinductivity in human BMSCs.

We obtained a range of PLGA-based composites containing sol-gel bioactive glasses (SBG) from the SiO2-CaO and SiO2-CaO-P2O5 systems. Eight SBGs with different CaO/SiO2 ratios with and without P2O5 were incorporated at 50% w/w to PLGA matrix and structured into thin films suitable for cell culture. The SBG/PLGA composites were examined for their bioactivity in simulated body fluid (SBF), ion release profile in culture media with and without cells, and osteoinductivity in standard human bone marrow stromal cell (hBMSC) cultures without osteogenic growth factors. Our results indicate different surface activity of composites depending on the presence/absence of P2O5 in SBG composition. Furthermore, ion release profile to culture medium differed depending on the presence/absence of cells. Direct culture of hBMSC on the SiO2-CaO/PLGA composite films resulted in elevated Runx-2 mRNA, opposite to low Runx-2 mRNA levels on SiO2-CaO-P2O5/PLGA films. All studied composites increased Osx mRNA levels. Whereas some of SiO2-CaO/PLGA composites did not elevate BMP-2 and -6 proteins in hBMSC cultures, high levels of these BMPs were present in all cultures on SiO2-CaO-P2O5/PLGA composites. All composites induced BMP-related Tak1 signalling, whereas Smad1 signalling was restricted mostly to composites containing three-component SBGs. ALP activity of hBMSC and BMP-related luciferase activity of mouse BRITE cells differed depending on whether the cells were stimulated with culture medium conditioned with SBG/PLGA composites or the cells were directly cultured on the composite surfaces. Altogether, beyond bioactivity and osteoinductivity of SBG/PLGA composites, our studies show key differences in the biological response to both the bioactive material dissolution products and upon direct cell-material contacts.