A NOVEL LITHIUM-DOPED 45S5 BIOACTIVE GLASS WITH POTENTIAL TO STIMULATE ANGIOGENESIS

VARGAS, GE; HARO DURAND, LA; VERA MESONES, R; FANOVICH, MA; GORUSTOVICH, A

Madrid

Congreso; Conference on Cardiovascular Development, Disease and Repair; 2013

CNIC

Recent experimental evidence shows that lithium (Li) stimulates the in vitro secretion of growth factors with pro-angiogenic activity. The controlled and localized release of Li ions from bioactive glasses might prove a promising therapeutic alternative to initiate angiogenesis and achieve neovascularization in tissue repair and/or regeneration procedures. The aim of this work was to assess the angiogenic effects of the ionic dissolution products of new bioactive glasses based on 45S5-type glass (% weight): 45% SiO2, 24.5% Na2O, 24.5% CaO, 6% P2O5 doped with 1% (45S5.1Li) or 5% Li2O (45S5.5Li). The ionic dissolution products were obtained by incubating 1% w/v particles (<5 µm) of bioactive glass in egg water at 37ºC in an orbital shaker for 72 h. The determination of soluble ions lixiviated from the bioactive glasses was conducted through inductively coupled plasma mass spectrometry (ICP-MS). In vivo angiogenesis assays were carried out on dechorionated zebrafish embryos (Danio rerio) at 48 h post fecundation (hpf). The embryos were incubated for 24 h at 28.5°C in 6-well culture plates containing either 5 mL egg water (control) or egg water enriched with the ionic dissolution products. We carried out 3 replicates with n=15 embryos per treatment. The embryos were anesthetized with tricaine and processed for the subsequent morphometric analysis of the subintestinal vascular plexus, through enzyme-histochemical identification of endogenous alkaline phosphatase, following the methodology described by Kamei et al (Methods Cell Biol 2010; 100:27-54). In all cases we observed the embryonic development expected for the incubation time assessed. The results obtained showed that only the ionic dissolution products of 45S5 bioactive glass doped with 5% Li2O (45S5.5Li) exhibited pro-angiogenic capability. The positive effects can be attributed to the release of 0.20 mM Li from 45S5.5Li microparticles.