Covalent conjugation of mechanically stiff graphene oxide flakes to three-dimensional collagen scaffolds for osteogenic differentiation of human mesenchymal stem cells
Covalent conjugation of mechanically stiff graphene oxide flakes to three-dimensional collagen scaffolds for osteogenic differentiation of human mesenchymal stem cells
复制标题
DOI：
10.1016/j.carbon.2014.11.029
复制
发表时间：
2015-03-01
期刊：
影响因子：
10.9
通讯作者：
Kim, Byung-Soo
中科院分区：
文献类型：
--
作者：
Kang, Seokyung;Park, Jong Bo;Kim, Byung-Soo
间充质干细胞(MSCs)在机械坚硬的基质上培养时，优先分化为成骨细胞。然而，作为临床批准的骨再生支架，胶原海绵为MSCs提供了柔软的微环境。在这里，我们证明了机械刚性氧化石墨烯(GO)薄片与三维(3D)胶原支架的共价连接改善了支架的力学性能，并促进了培养在支架上的人MSCs(HMSCs)的成骨分化。GO片材与胶原支架的共价偶联使支架的硬度提高了3倍，且不产生细胞毒性。与未修饰的胶原支架上培养的细胞相比，在GO-胶原支架上培养的hMSCs具有明显的成骨分化作用。在较硬的支架上观察到的增强的成骨分化可能是由MSC机械传感介导的，因为参与细胞与硬基质黏附的分子要么上调，要么被激活。这种3D GO-胶原支架可以为干细胞研究和整形外科再生医学提供一个强大的平台。(C)2014爱思唯尔有限公司。保留所有权利。
Mesenchymal stem cells (MSCs) preferentially differentiate to osteogenic lineage when cultured on mechanically stiff substrates. However, collagen sponges, clinically approved scaffolds for bone regeneration, provide soft microenvironment to MSCs. Here, we demonstrate that the covalent conjugation of mechanically stiff graphene oxide (GO) flakes to three-dimensional (3D) collagen scaffolds improves the mechanical properties of the scaffolds and promotes the osteogenic differentiation of human MSCs (hMSCs) cultured on the scaffolds. The covalent conjugation of GO flakes to collagen scaffolds increased the scaffold stiffness by 3-fold and did not cause cytotoxicity. hMSCs cultured on the GO-collagen scaffolds demonstrated significantly enhanced osteogenic differentiation compared to cells cultured on non-modified collagen scaffolds. The enhanced osteogenic differentiation observed on the stiffer scaffolds was likely mediated by MSC mechanosensing because molecules that are involved in cell adhesion to stiff substrates were either up-regulated or activated. The 3D GO-collagen scaffolds could offer a powerful platform for stem cell research and orthopedic regenerative medicine. (C) 2014 Elsevier Ltd. All rights reserved.