Caracterização estrutural e avaliação in vitro e in vivo do estímulo angiogênico do cobalto incorporado em vidro bioativo e desenvolvimento de scaffolds híbridos de poli (álcool vinílico) / vidro bioativo contendo cobalto

Abstract

Angiogenesis has been studied in therapies such as the treatment of peripheral vascular insufficiency, antigenic therapies and reduction of blood flow that can compromise tissues, and it is also an important process in tissue regeneration approaches using biomaterials. Biomaterials comprise a representative fraction of the products used in the health area. Among these, bioactive glasses (BGs) have demonstrated flexibility in composition that allows the incorporation of different ions with physiological activities and therapeutic properties. Cobalt (Co) is a therapeutic ion that stimulates the formation of new blood vessels by activating vascular endothelial growth factor A (VEGFA), and by the hypoxia inducible factor 1 subunit A (HIF1A). Hybrid scaffolds made of poly (vinyl alcohol) and bioactive glass appear as a promising strategy to accelerate bone tissue repair. However, the effects of glasses incorporated with Co on angiogenesis need to be investigated in more detail. There are also no studies on hybrid scaffolds, using the sol-gel method and a foaming method, with the direct incorporation of the therapeutic ion cobalt. In this context, this work aimed to develop, characterize and evaluate BGs derived from the sol-gel process, containing cobalt in its structure, and of hybrid scaffolds containing Co. Structural analyzes confirmed the presence of Co in the structure of bioactive glasses and hybrid scaffolds. The in vitro viability of cells exposed to different concentrations of the ionic product (IP) of the materials has not been altered. It was demonstrated, through the tube formation test with HUVECS, that the IP of the BG containing 2.5%Co mimics the performance of VEGFA in the induction of blood vessels formation. It was also observed an increase in the expression of the VEGFA and H1F1A genes, after 14 hours of contact with the IP. Through in vivo studies in Wistar rats, it was shown that the BG incorporated with Co in its structure was able to increase the expression of VEGFA and H1F1A, characterizing a stimulation of the angiogenesis process due to the release of Co. For the hybrid scaffolds after the incorporation of Co, the formation of hydroxyapatite and excellent cell viability were observed in in vitro tests. The incorporation of Co in BGs and hybrid scaffolds proved to be a promising strategy to improve its potential for angiogenesis and tissue engineering.