Bone regeneration in sheep model induced by strontium-containing mesoporous bioactive glasses

Abstract

Local delivery of therapeutic ions from bioactive mesoporous glasses (MBGs) is postulated as one of the most promising strategies for regenerative therapy of critical bone defects. Among these ions, Sr²⁺ cation has been widely considered for this purpose as part of the composition of MBGs. MBGs of chemical composition 75SiO₂-25-x CaO-5P₂O₅-xSrO with x = 0, 2.5 and 5 (% mol) were prepared by the evaporation induced self-assembly (EISA) method. Strontium incorporation did not affect the apatite forming ability of Sr-free MBG when these bioceramics are treated with simulated body fluid (SBF). In vitro cell viability showed that proliferation of MC3T3-E1 preosteoblast is not affected by the presence of Sr²⁺ cations, whereas ALP activity and gene expression of Runx2, ALP and VEGF is increased as a function of Sr content. Besides, cell proliferation and VEGF expression of HUVEC cells were also increased with the Sr²⁺ content. In this work, we present for the first time the effects of Sr containing MBGs on bone regeneration in a large animal model (sheep), after implantation in a cavitary defect. The histomorphometrical analysis and immunohistochemistry indicate that the incorporation of Sr²⁺ ion greatly enhances the osteoregenerating potential of MBGs. In this sense, the measured ossification areas were 7 % and 20 % for MBG and Sr-MBG, respectively. Besides, the thickness of the newly formed trabeculae was 15 μm and 30 μm for MBG and Sr-MBG, respectively. This enhancement of Sr²⁺ mediated bone formation would be justified by the transient osteoclastogenesis inhibition and the osteogenesis-angiogenesis increase due to the endothelial cell proliferation and increased vascular endothelial growth factor expression.