Graphene oxide-functionalized nanocomposites promote osteogenesis of human mesenchymal stem cells via enhancement of BMP-SMAD1/5 signaling pathway.
Graphene oxide-functionalized nanocomposites promote osteogenesis of human mesenchymal stem cells via enhancement of BMP-SMAD1/5 signaling pathway.
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DOI：
10.1016/j.biomaterials.2021.121082
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发表时间：
2021-10
期刊：
影响因子：
14
通讯作者：
Lin H
中科院分区：
文献类型：
--
作者：
Li Z;Xiang S;Lin Z;Li EN;Yagi H;Cao G;Yocum L;Li L;Hao T;Bruce KK;Fritch MR;Hu H;Wang B;Alexander PG;Khor KA;Tuan RS;Lin H
能够利用干细胞内在成骨潜能的生物材料为加速骨再生和修复提供了一种有前途的策略。以前，我们使用甲基丙烯酸明胶（GelMA）为基础的支架，以实现从人骨髓间充质干细胞（hMSCs）的骨形成。在这项研究中，我们的目的是通过将基于氧化石墨烯（GO）的纳米片掺入GelMA中来进一步增强hMSC成骨。体外实验结果表明，包封在新开发的纳米复合材料中的hMSCs具有高活力和代谢活性。GO的掺入显著增加了载有hMSC的构建体内的矿化，这通过用二氧化硅涂覆的氧化石墨烯（SiGO）替代GO而进一步增加。机制分析表明，纳米片增强了内源性骨形态发生蛋白（BMP）的产生、保留和生物活性，从而在不存在外源性骨诱导生长因子的情况下实现稳健的成骨。具体地，通过用LDN-193189处理抑制BMP信号传导途径来消除纳米片的骨诱导作用。使用小鼠皮下植入模型在体内进一步测试该技术的骨形成潜力，其中载有hMSC的GO/GelMA和SiGO/GelMA样品分别导致比GelMA对照组大108倍和385倍的骨体积。总之，这些结果证明了基于GO的纳米片在增强hMSC的成骨能力方面的生物活性和作用机制，并突出了利用纳米材料如GO和SiGO用于骨组织工程应用的潜力。这项研究证明了氧化石墨烯纳米片在增强骨再生中的作用机制。
Biomaterials that can harness the intrinsic osteogenic potential of stem cells offer a promising strategy to accelerate bone regeneration and repair. Previously, we had used methacrylated gelatin (GelMA)-based scaffolds to achieve bone formation from human mesenchymal stem cells (hMSCs). In this study, we aimed to further enhance hMSC osteogenesis by incorporating graphene oxide (GO)-based nanosheets into GelMA. In vitro results showed high viability and metabolic activities in hMSCs encapsulated in the newly developed nanocomposite. Incorporation of GO markedly increased mineralization within hMSC-laden constructs, which was further increased by replacing GO with silica-coated graphene oxide (SiGO). Mechanistic analysis revealed that the nanosheet enhanced the production, retention, and biological activity of endogenous bone morphogenetic proteins (BMPs), resulting in robust osteogenesis in the absence of exogenous osteoinductive growth factors. Specifically, the osteoinductive effect of the nanosheets was abolished by inhibiting the BMP signaling pathway with LDN-193189 treatment. The bone formation potential of the technology was further tested in vivo using a mouse subcutaneous implantation model, where hMSCs-laden GO/GelMA and SiGO/GelMA samples resulted in bone volumes 108 and 385 times larger, respectively, than the GelMA control group. Taken together, these results demonstrate the biological activity and mechanism of action of GO-based nanosheets in augmenting the osteogenic capability of hMSCs, and highlights the potential of leveraging nanomaterials such as GO and SiGO for bone tissue engineering applications. This study demonstrates the mechanism of action of graphene oxide nanosheets in augmenting bone regeneration.
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