Multi-targeted B and Co co-doped 45S5 bioactive glasses with angiogenic potential for bone regeneration

Many elements, such as copper, cobalt (Co), strontium, magnesium and boron (B) have been used for single or multiple doping of bioactive glasses to promote angiogenesis during bone regeneration. However, few works have focused on promoting angiogenesis through stimulating several different signalling pathways which can be called a multi-target approach. In this study, 45S5 bioactive glass (BG) co-doped with B and Co was prepared by conventional melt quenching method. The synergistic effect of the two co-doping elements on angiogenesis promotion was expected. ATR-Fourier transform infrared spectroscopy, energy-dispersive X-ray spectroscopy and inductively coupled plasma-optical emission spectrometry were used to characterize the composition, element distribution and ion release of the samples, respectively. Results showed that the compositions of all samples were consistent with the design compositions and all elements were homogeneously distributed in the bulk glass. Different contents of B and Co led to different release rates of these elements. All samples showed bioactivity after immersion in simulated body fluid, regardless of the amount of doped B and Co. The 1% and 0.1% extracts of all samples did not show any cytotoxicity to MG-63 and ST-2 cells. Compared with single B or Co doping, the B and Co dual doped sample led to a stronger increase of the secretion of vascular endothelial growth factor from ST-2 cells, which supports and confirms the synergistic effect on angiogenesis of B and Co as co-doping elements in 45S5 BG.