Müller Werner E G, Tolba Emad, Ackermann Maximilian, Neufurth Meik, Wang Shunfeng, Feng Qingling, Schröder Heinz C, Wang Xiaohong
ERC Advanced Investigator Grant Research Group at the Institute for Physiological Chemistry, University Medical Center of the Johannes Gutenberg University, Duesbergweg 6, D-55128 Mainz, Germany.
ERC Advanced Investigator Grant Research Group at the Institute for Physiological Chemistry, University Medical Center of the Johannes Gutenberg University, Duesbergweg 6, D-55128 Mainz, Germany.
Acta Biomater. 2017 Mar 1;50:89-101. doi: 10.1016/j.actbio.2016.12.045. Epub 2016 Dec 23.
Here we describe the fabrication process of amorphous strontium-polyphosphate microparticles ("Sr-a-polyP-MP"). The effects of these particles on growth and gene expression were investigated with SaOS-2 cells as well as with human mesenchymal stem cells (MSC) and compared with those particles prepared of amorphous calcium-polyphosphate ("Ca-a-polyP-MP") and of strontium salt. The results revealed a markedly higher stimulation of growth of MSC by "Sr-a-polyP-MP" compared to "Ca-a-polyP-MP" and a significant increase in mineralization of SaOS-2 cells, as well as an enhanced upregulation of the expression of the genes encoding for alkaline phosphatase and the bone morphogenetic protein 2 (BMP-2), likewise performed with SaOS-2 cells. On the other hand, "Sr-a-polyP-MP" only slightly changes the expression of the osteocyte-specific sclerostin, a negative regulator of the canonical Wnt signaling pathway and an inhibitor of bone cell differentiation as well as of mineralization in SaOS-2 cells. In contrast, "Ca-a-polyP-MP" strongly increased the steady-state expression of the SOST (sclerostin) gene. In animal studies poly(d,l-lactide-co-glycolide (PLGA) microspheres, containing polyP particles, were implanted into critical-size calvarial defects in rats. The results show that the amorphous Sr-polyP-containing microspheres caused an increased healing/mineralization of the bone defect even after short implantation periods of 8-12weeks, if compared to the β-tri-calcium phosphate control as well as to Ca-polyP. It is proposed that "Sr-a-polyP-MP" might elicit suitable properties to be applied as a regeneratively active implant material for bone repair.
In this manuscript, we fabricated amorphous strontium-polyphosphate microparticles ("Sr-a-polyP-MP") and studied their effects on bone mineral formation in vitro as well as in vivo. In vitro, those particles substantially increased the expression of the genes encoding for alkaline phosphatase, the bone morphogenetic protein 2 and the mineralization. In vivo, the "Sr-a-polyP-MP" packed into PLGA microspheres and implanted into critical-size calvarial defects in rats resulted in a speeded up of the healing/mineralization of the bone defect. Those properties qualify Sr-a-polyP as a suitable biomaterial for bone regenerative implants.
在此，我们描述了无定形锶 - 聚磷酸盐微粒（“Sr - a - polyP - MP”）的制备过程。以SaOS - 2细胞以及人间充质干细胞（MSC）研究了这些微粒对细胞生长和基因表达的影响，并与由无定形钙 - 聚磷酸盐（“Ca - a - polyP - MP”）和锶盐制备的微粒进行了比较。结果显示，与“Ca - a - polyP - MP”相比，“Sr - a - polyP - MP”对MSC生长的刺激作用明显更高，并且SaOS - 2细胞的矿化显著增加，同时在SaOS - 2细胞中，编码碱性磷酸酶和骨形态发生蛋白2（BMP - 2）的基因表达上调增强。另一方面，“Sr - a - polyP - MP”仅轻微改变骨细胞特异性硬化蛋白的表达，硬化蛋白是经典Wnt信号通路的负调节因子，也是骨细胞分化和SaOS - 2细胞矿化的抑制剂。相比之下，“Ca - a - polyP - MP”强烈增加了SOST（硬化蛋白）基因的稳态表达。在动物研究中，将含有聚P微粒的聚（d，l - 丙交酯 - 共 - 乙交酯）（PLGA）微球植入大鼠临界尺寸的颅骨缺损处。结果表明，与β - 磷酸三钙对照以及Ca - polyP相比，即使在短至8 - 12周的植入期后，含无定形Sr - polyP的微球也能使骨缺损的愈合/矿化增加。有人提出，“Sr - a - polyP - MP”可能具有适合作为骨修复的再生活性植入材料的特性。
在本论文中，我们制备了无定形锶 - 聚磷酸盐微粒（“Sr - a - polyP - MP”），并研究了它们在体外和体内对骨矿物质形成的影响。在体外，这些微粒显著增加了编码碱性磷酸酶、骨形态发生蛋白2的基因表达以及矿化。在体内，装入PLGA微球并植入大鼠临界尺寸颅骨缺损处的“Sr - a - polyP - MP”导致骨缺损的愈合/矿化加速。这些特性使Sr - a - polyP成为骨再生植入物的合适生物材料。
