Ionic dissolution products of Cerium-doped bioactive glass nanoparticles promote cellular osteogenic differentiation and extracellular matrix formation of human bone marrow derived mesenchymal stromal cells
Fabian Westhauser, Felix Rehder, Simon Decker, Elke Kunisch, Arash Moghaddam, Kaifu Zheng, Aldo R. Boccaccini
Abstract
Abstract Cerium (Ce) is a promising candidate ion for application in bone tissue engineering (BTE) since it reduces the presence of reactive oxygen species. Ce-doped mesoporous bioactive glass nanoparticles (MBGNs) serving as vectors for the local application of Ce already demonstrated stimulating effects on the expression of pro-osteogenic genes in Saos-2 cells. So far, there is no evidence available about the effects of Ce-doped MBGNs on the viability, osteogenic differentiation and the formation of the osseous extracellular matrix (ECM) of primary human bone marrow-derived mesenchymal stromal cells (BMSCs). Therefore, in this study, the biocompatibility of the ionic dissolution products (IDPs) of MBGNs containing increasing concentrations of CeO 2 (0.05 MCe-MBGNs, composition in mol%: 86.6SiO 2 -12.1CaO-1.3CeO 2 ; and 0.2 MCe-MBGNs, composition in mol%: 86.0SiO 2 -11.8CaO-2.2CeO 2 ) and unmodified MBGNs (composition in mol%: 86SiO 2 -14CaO) was evaluated using human BMSCs. Eventually, the impact of the MBGNs’ IDPs on the cellular osteogenic differentiation and their ability to build and mature a primitive osseous ECM was assessed. The Ce-doped MBGNs had a positive influence on the viability and stimulated the cellular osteogenic differentiation of human BMSCs evaluated by analyzing the activity of alkaline phosphate as a marker enzyme for osteoblasts in the present setting. Furthermore, the formation and calcification of a primitive osseous ECM was significantly stimulated in the presence of Ce-doped MBGNs in a positive concentration-dependent manner as demonstrated by an elevated presence of collagen and increased ECM calcification. The results of this in-vitro study show that Ce-doped MBGNs are attractive candidates for further application in BTE.