Jiménez-Holguín Javier, Lozano Daniel, Saiz-Pardo Melchor, de Pablo David, Ortega Luis, Enciso Silvia, Fernández-Tomé Blanca, Díaz-Güemes Idoia, Sánchez-Margallo Francisco Miguel, Portolés María Teresa, Arcos Daniel
Departamento de Química en Ciencias Farmacéuticas, Facultad de Farmacia, Universidad Complutense de Madrid, Instituto de Investigación Sanitaria Hospital 12 de Octubre i+12, Plaza Ramón y Cajal s/n, 28040 Madrid, Spain.
Departamento de Química en Ciencias Farmacéuticas, Facultad de Farmacia, Universidad Complutense de Madrid, Instituto de Investigación Sanitaria Hospital 12 de Octubre i+12, Plaza Ramón y Cajal s/n, 28040 Madrid, Spain; CIBER de Bioingeniería, Biomateriales y Nanomedicina, Instituto de Salud Carlos III, 28040 Madrid, Spain.
Biomater Adv. 2025 Apr;169:214168. doi: 10.1016/j.bioadv.2024.214168. Epub 2024 Dec 30.
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, Sr cation has been widely considered for this purpose as part of the composition of MBGs. MBGs of chemical composition 75SiO-25-x CaO-5PO-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 Sr 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 Sr 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 Sr 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 Sr 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.
从生物活性介孔玻璃（MBG）中局部递送治疗性离子被认为是治疗严重骨缺损再生疗法中最具前景的策略之一。在这些离子中，Sr阳离子作为MBG成分的一部分，已被广泛用于此目的。通过蒸发诱导自组装（EISA）法制备了化学组成为75SiO₂ - 25 - xCaO - 5PO₄ - xSrO（x = 0、2.5和5（mol%））的MBG。当这些生物陶瓷用模拟体液（SBF）处理时，锶的掺入并不影响无锶MBG的磷灰石形成能力。体外细胞活力表明，MC3T3 - E1前成骨细胞的增殖不受Sr阳离子存在的影响，而碱性磷酸酶（ALP）活性以及Runx2、ALP和血管内皮生长因子（VEGF）的基因表达随Sr含量增加而升高。此外，人脐静脉内皮细胞（HUVEC）的细胞增殖和VEGF表达也随Sr含量增加。在这项工作中，我们首次展示了含Sr的MBG在植入腔洞性缺损后，对大型动物模型（绵羊）骨再生的影响。组织形态计量学分析和免疫组织化学表明，Sr离子的掺入极大地增强了MBG的骨再生潜力。从这个意义上说，MBG和含Sr - MBG的测量骨化面积分别为7%和20%。此外，MBG和含Sr - MBG新形成小梁的厚度分别为15μm和30μm。Sr介导的骨形成增强可能是由于破骨细胞生成的短暂抑制以及由于内皮细胞增殖和血管内皮生长因子表达增加导致的成骨 - 血管生成增加。
