Cobalt-containing bioactive glass mimics vascular endothelial growth factor A and hypoxia inducible factor 1 function.

Bioactive glasses (BGs) have shown great potential for tissue regeneration and their composition flexibility allows the incorporation of different ions with physiological activities and therapeutic properties in the glass network. Among the many ions that could be incorporated, cobalt (Co) is a significant one, as it mimics hypoxia, triggering the formation of new blood vessels by the vascular endothelial growth factor A (VEGFA), due to the stabilizing effect on the hypoxia inducible factor 1 subunit alpha (HIF1A), an activator of angiogenesis-related genes, and is therefore of great interest for tissue engineering applications. However, despite its promising properties, the effects of glasses incorporated with Co on angiogenesis, through human umbilical cord vein endothelial cells (HUVECs) studies, need to be further investigated. Therefore, this work aimed to evaluate the biocompatibility and angiogenic potential of a new sol-gel BG, derived from the SiO2 -CaO-P2 O5 -CoO system. The structural evaluation showed the predominance of an amorphous glass structure, and the homogeneous presence of cobalt in the samples was confirmed. in vitro experiments showed that Co-containing glasses did not affect the viability of HUVECs, stimulated the formation of tubes and the gene expression of HIF1A and VEGFA. in vivo experiments showed that Co-containing glasses stimulated VEGFA and HIF1A expression in blood vessels and cell nuclei, respectively, in the deep dermis layer of the dorsal region of rats, featuring considerable local stimulation of the angiogenesis process due to Co-release. Co-containing glasses showed therapeutic effect, and Co incorporation is a promising strategy for obtaining materials with superior angiogenesis properties for tissue engineering applications.

Synthesis, characterization and cytocompatibility of spherical bioactive glass nanoparticles for potential hard tissue engineering applications.

Nanotechnology offers a new strategy to develop novel bioactive materials, given that nano-scaled biomaterials exhibit an enhanced biocompatibility and bioactivity. In this work, we developed a method for the synthesis of spherical bioactive glass nanoparticles (BGNP) aimed at producing biomaterials for potential use in the repair of hard tissues. The BGNP were prepared using the sol-gel process based on the reaction of alkoxides and other precursors in aqueous media for obtaining the oxide-ternary system with the stoichiometric proportion of 60% SiO2, 36% CaO and 4% P2O5. The system was extensively characterized by Fourier transform infrared, x-ray diffraction and scanning electron microscope/energy-dispersive x-ray spectroscopy with regard to chemical composition, crystallinity and morphology. Moreover, the results suggested the BGNP to be highly bioactive, which was confirmed by the formation of a hydroxyapatite biomimetic layer on the material surfaces upon immersion in simulated body fluid solution. In addition, the bioactivity response toward the developed BGNPs was assessed by direct contact of osteoblast cells using resazurin and alkaline phosphatase assays. The new BGNP have presented a significant increase in the osteoblast in vitro cytocompatibility behavior as compared to similar micro-sized bioactive glass particles. Such improvement in the overall bioactive behavior of BGNP was attributed to the much higher surface area causing enhanced interactions at the cell-nanomaterial interfaces. Hence, based on the results, the BGNP produced are the biomaterials to be potentially utilized in hard tissue engineering applications.