Osteogenic-angiogenic coupled response of cobalt-containing mesoporous bioactive glasses in vivo

Abstract

The incorporation of cobalt ions into the composition of bioactive glasses has emerged as a strategy of interest for bone regeneration purposes. In the present work, we have designed a set of bioactive mesoporous glasses SiO2 -CaO-P2 O5 -CoO (Co-MBGs) with different amounts of cobalt. The physicochemi- cal changes introduced by the Co2 + ion, the in vitro effects of Co-MBGs on preosteoblasts and endothelial cells and their in vivo behaviour using them as bone grafts in a sheep model were studied. The results show that Co2 + ions neither destroy mesoporous ordering nor inhibit in vitro bioactive behaviour, ex- erting a dual role as network former and modifier for CoO concentrations above 3 % mol. On the other hand, the activity of Co-MBGs on MC3T3-E1 preosteoblasts and HUVEC vascular endothelial cells is de- pendent on the concentration of CoO present in the glass. For low Co-MBGs concentrations (1mg/ml) cell viability is not affected, while the expression of osteogenic (ALP, RUNX2 and OC) and angiogenic (VEGF) genes is stimulated. For Co-MBGs concentration of 5 mg/ml, cell viability decreases as a function of the CoO content. In vivo studies show that the incorporation of Co2 + ions to the MBGs improves the bone regeneration activity of these materials, despite the deleterious effect that this ion has on bone-forming cells for any of the Co-MBG compositions studied. This contradictory effect is explained by the marked increase in angiogenesis that takes place inside the bone defect, leading