Department of Prosthodontics, Oral Bioengineering and regenerative medicine Lab, Ninth People's Hospital affiliated to Shanghai Jiao, Tong University, School of Medicine, 639 Zhizaoju Road, Shanghai, 200011, China.
Clinical Research Center, Shanghai Jiading Central Hospital, 1 Chengbei Road, Shanghai, 201800, China.
Adv Healthc Mater. 2016 Jun;5(11):1299-309. doi: 10.1002/adhm.201500824. Epub 2016 Mar 4.
Graphene has been studied for its in vitro osteoinductive capacity. However, the in vivo bone repair effects of graphene-based scaffolds remain unknown. The aqueous soluble graphene oxide-copper nanocomposites (GO-Cu) are fabricated, which are used to coat porous calcium phosphate (CaP) scaffolds for vascularized bone regeneration. The GO-Cu nanocomposites, containing crystallized CuO/Cu2 O nanoparticles of ≈30 nm diameters, distribute uniformly on the surfaces of the porous scaffolds and maintain a long-term release of Cu ions. In vitro, the GO-Cu coating enhances the adhesion and osteogenic differentiation of rat bone marrow stem cells (BMSCs). It is also found that by activating the Erk1/2 signaling pathway, the GO-Cu nanocomposites upregulate the expression of Hif-1α in BMSCs, resulting in the secretion of VEGF and BMP-2 proteins. When transplanted into rat with critical-sized calvarial defects, the GO-Cu-coated calcium phosphate cement (CPC) scaffolds (CPC/GO-Cu) significantly promote angiogenesis and osteogenesis. Moreover, it is observed via histological sections that the GO-Cu nanocomposites are phagocytosed by multinucleated giant cells. The results suggest that GO-Cu nanocomposite coatings can be utilized as an attractive strategy for vascularized bone regeneration.
石墨烯的体外成骨能力已经得到了研究。然而，基于石墨烯的支架在体内的骨修复效果尚不清楚。我们制备了水溶性氧化石墨烯-铜纳米复合材料（GO-Cu），并用其来涂覆多孔磷酸钙（CaP）支架，以实现血管化骨再生。GO-Cu 纳米复合材料含有约 30nm 直径的结晶化 CuO/Cu2O 纳米颗粒，均匀分布在多孔支架的表面，并能持续释放 Cu 离子。体外实验表明，GO-Cu 涂层能增强大鼠骨髓基质干细胞（BMSCs）的黏附与成骨分化。我们还发现，GO-Cu 纳米复合材料通过激活 Erk1/2 信号通路，上调 BMSCs 中 Hif-1α 的表达，从而促进 VEGF 和 BMP-2 蛋白的分泌。将 GO-Cu 涂覆的磷酸钙骨水泥（CPC/GO-Cu）支架移植到大鼠临界颅骨缺损模型中，能显著促进血管生成和骨生成。此外，组织切片观察到多核巨细胞吞噬了 GO-Cu 纳米复合材料。这些结果表明，GO-Cu 纳米复合材料涂层可用作一种有吸引力的血管化骨再生策略。
