Osteogenic differentiation and immune response of human bone-marrow-derived mesenchymal stem cells on injectable calcium-silicate-based bone grafts

Calcium silicate cement (CSC) is biocompatible and possesses in vitro bioactivity. The aim of this study was to improve the handling and enhance osteogenic and immune properties of CSC by the addition of adjuvants to modify the cement. Human bone-marrow-derived mesenchymal stem cells were used to study the osteogenic behavior and immune response of cells on hybrid cements with added gelatin (GLT) and chitosan oligosaccharides (COS), which are analogs of the extracellular matrix components collagen and glycosaminoglycan, respectively. The addition of COS to the liquid phase slightly prolonged the setting time of CSC, whereas GLT in the solid phase significantly (p<0.05) extended the hydration reaction. However, the addition of GLT appreciably improved the injectability of CSC, compared to COS. Cell viability was higher on CSC-COS than on the CSC control or on CSC-GLT at all culture times. The hybrid bone cements elicited less immune response than the CSC control. Additionally, COS inhibited expression of inducible nitric oxide synthase and interleukin-1 and activated interleukin-10 more effectively than GLT. Osteocalcin production and bone sialoprotein production were higher, and more calcium was detected in human bone-marrow-derived mesenchymal stem cells cultured on a CSC-GLT-COS surface than on CSC, CSC-GLT, or CSC-COS. These synergistic improvements in injectability, immune response, and osteogenesis suggest that the combination of bioactive calcium silicate, GLT, and COS has potential for use in clinical applications.