In regenerative medicine of vascularized tissues, there is a great interest in the use of biomaterials that are able to stimulate angiogenesis, a process necessary for rapid revascularization to allow the transport and exchange of oxygen, nutrients, growth factors and cells that take part in tissue repair and/or regeneration. An increasing number of publications have shown that bioactive glasses stimulate angiogenesis. Because it has been established that boron (B) may play a role in angiogenesis, the aim of this study was to assess the in vivo angiogenic effects of the ionic dissolution products that from a bioactive glass (BG) in the 45S5 system doped with 2 wt% B 2 O 3 (45S5.2B). The pro-angiogenic capacity of 45S5.2B BG was assessed on the vasculature of the embryonic quail chorioallantoic membrane (CAM).Ionic dissolution products from 45S5.2B BG increased angiogenesis. This is quantitatively evidenced by the greater expression of integrin a v b 3 and higher vascular density in the embryonic quail CAM. The response observed at 2 and 5 days post-treatment was equivalent to that achieved by applying 10 mg mL À1 of basic fibroblast growth factor. These results show that the ionic dissolution products released from the bioactive glass 45S5.2B stimulate angiogenesis in vivo. The effects observed are attributed to the presence the ionic dissolution products, which contained 160 AE 10 mM borate.

Since lithium (Li+) plays roles in angiogenesis, the localized and controlled release of Li+ ions from bioactive glasses (BGs) represents a promising alternative therapy for the regeneration and repair of tissues with a high degree of vascularization. Here, microparticles from a base 45S5 BG composition containing (wt %) 45% SiO2, 24.5% Na2O, 24.5% CaO, and 6% P2O5, in which Na2O was partially substituted by 5% Li2O (45S5.5Li), were obtained. The results demonstrate that human umbilical vein endothelial cells (HUVECs) have greater migratory and proliferative response and ability to form tubules in vitro after stimulation with the ionic dissolution products (IDPs) of the 45S5.5Li BG. The results also show the activation of the canonical Wnt/β-catenin pathway and the increase in expression of proangiogenic cytokines insulin like growth factor 1 (IGF1) and transforming growth factor beta (TGFβ). We conclude that the IDPs of 45S5.5Li BG would act as useful inorganic agents to improve tissue repair and regeneration, ultimately stimulating HUVECs behavior in the absence of exogenous growth factors.