Department of Orthopedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China,
The Education Ministry Key Lab of Resource Chemistry, Shanghai Key Laboratory of Rare Earth Functional Materials, Shanghai Normal University, Shanghai 200234, China,
Int J Nanomedicine. 2019 Feb 11;14:1085-1100. doi: 10.2147/IJN.S193576. eCollection 2019.
Biomaterial-induced osteogenesis is mainly related to hierarchically porous structures and bioactive components. Rare earth elements are well known to promote osteogenesis and stimulate bone repair; however, the underlying biological effects of gadolinium (Gd) element on bone regeneration are not yet known.
In this study, we successfully fabricated gadolinium-doped bioglass (Gd-BG) scaffolds by combining hollow mesoporous Gd-BG microspheres with chitosan and evaluated in vitro effects and underlying mechanisms with Cell Counting Kit-8, scanning electron microscopy, alkaline phosphatase, Alizarin red staining, and polymerase chain reaction. Cranial defect model of rats was constructed to evaluate their in vivo effects.
The results indicated that Gd-BG scaffolds could promote the proliferation and osteogenic differentiation of human bone marrow-derived mesenchymal stem cells (hBMSCs). Mechanistically, the Akt/GSK3β signaling pathway was activated by the Gd-BG scaffolds. The enhancing effect of Gd-BG scaffolds on the osteogenic differentiation of hBMSCs was inhibited by the addition of LY294002, an inhibitor of Akt. Moreover, the in vivo cranial defect model of rats indicated that the Gd-BG scaffolds could effectively promote bone regeneration.
Both in vitro and in vivo results suggested that Gd-BG scaffolds have promising applications in bone tissue engineering.
生物材料诱导成骨主要与分级多孔结构和生物活性成分有关。众所周知，稀土元素能促进成骨并刺激骨修复；然而，钆（Gd）元素对骨再生的潜在生物学效应尚不清楚。
在这项研究中，我们成功地通过将中空介孔 Gd-BG 微球与壳聚糖结合，制备了掺钆生物玻璃（Gd-BG）支架，并通过细胞计数试剂盒-8、扫描电子显微镜、碱性磷酸酶、茜素红染色和聚合酶链反应评估了其体外效应和潜在机制。构建大鼠颅缺损模型来评估其体内效应。
结果表明，Gd-BG 支架可以促进人骨髓间充质干细胞（hBMSCs）的增殖和成骨分化。在机制上，Gd-BG 支架激活 Akt/GSK3β 信号通路。通过添加 Akt 的抑制剂 LY294002，抑制了 Gd-BG 支架对 hBMSCs 成骨分化的增强作用。此外，大鼠体内颅缺损模型表明，Gd-BG 支架能有效促进骨再生。
体内外结果均表明，Gd-BG 支架在骨组织工程中有广阔的应用前景。
