Borosilicate bioactive glasses with added Mg/Sr enhances human adipose-derived stem cells osteogenic commitment and angiogenic properties

Abstract

<p>Bioactive glasses are one of the most promising materials for applications in bone tissue engineering. In this study, the focus was on borosilicate bioactive glasses with composition 47.12 SiO<sub>2</sub> - 6.73 B<sub>2</sub>O<sub>3</sub> - 21.77-x-y CaO - 22.65 Na<sub>2</sub>O - 1.72 P<sub>2</sub>O<sub>5</sub> - x MgO - y SrO (mol%). These compositions are based on silicate S53P4 bioactive glass, from where 12.5% of SiO<sub>2</sub> is replaced with B<sub>2</sub>O<sub>3</sub>, and additionally, part of CaO is substituted for MgO and/or SrO. The impact of ion release, both as extract and in direct contact, on human adipose-derived stem cells’ (hADSCs) viability, proliferation, ECM maturation, osteogenic commitment and endothelial marker expression was assessed. Osteogenic media supplements were utilized with the extracts, and in part of the direct cell/material culturing conditions. While it has been reported in other studies that boron release can induce cytotoxicity, the glasses in this study supported cells viability and proliferation. Moreover, borosilicate’s, especially with further Mg/Sr substitutions, upregulated several osteogenic markers (such as RUNX2a, OSTERIX, DLX5, OSTEOPONTIN), as well as angiogenic factors (e.g., vWF and PECAM-1). Furthermore, the studied glasses supported collagen-I production even in the absence of osteogenic supplements, when hADSCs were cultured in contact with the glasses, suggesting that while the bioactive glass degradation products are beneficial for osteogenesis, the glasses surface physico-chemical properties play a significant role on hADSCs differentiation. This study brings critical information on the impact of bioactive glass compositional modification to control glass dissolution and the subsequent influence on stem cells proliferation and differentiation. Furthermore, the role of the material surface chemistry on promoting cell differentiation is reported. Graphical Abstract: (Figure presented.)</p>