Osteogenic and angiogenic potential of molybdenum-containing mesoporous bioactive glass nanoparticles: An ionic approach to bone tissue engineering

Biomaterials intended for application in bone tissue engineering (BTE) ideally stimulate osteogenesis and angiogenesis simultaneously, as both mechanisms are of critical importance for successful bone regeneration. Mesoporous bioactive glass nanoparticles (MBGNs) can be tailored towards specific biological needs, for example by addition of ions like Molybdenum (Mo). While Mo has been shown to enhance osteogenic differentiation of human bone marrow-derived mesenchymal stromal cells (BMSCs) as well as their ability to form and mature a primitive osseous extracellular matrix (ECM), there are contradictory findings regarding its impact on angiogenesis. In this study, the effects of Mo-MBGNs (mol%: 70 SiO₂, 25 CaO, 5 MoO₃) on viability, proliferation, osteogenic differentiation, ECM formation and angiogenic response of BMSCs were compared to undoped MBGNs (in mol%: 70 SiO₂, 30 CaO) and a control group of BMSCs. Furthermore, a human umbilical vein endothelial cells tube formation assay and a chorioallantoic membrane-assay using fertilized chicken eggs were used to analyze angiogenic properties. Mo-MBGNs were cytocompatible and promoted the proliferation of BMSCs. Furthermore, Mo-MBGNs showed promising osteogenic properties as they enhanced osteogenic differentiation, ECM formation and maturation as well as the gene expression and protein production of relevant osteogenic factors in BMSCs. However, despite the promising outcome on osteogenic properties, the addition of Mo to MBGNs resulted in anti-angiogenic effects. Due to the high relevance of vascularization in-vivo, the anti-angiogenic properties of Mo-MBGNs might hamper their osteogenic properties and therefore might restrict their performance in BTE applications. These limitations can be overcome by the addition of ions with distinct pro-angiogenic properties to the Mo-MBGNs-composition. Due to their promising osteogenic properties, Mo-MBGNs constitute a suitable basis for further research in the field of ionic (growth factor free) BTE.