Deting Xue,1,* Erman Chen,1,* Huiming Zhong,2,* Wei Zhang,1 Shengdong Wang,1 Muhammad Umar Joomun,1 Tianyi Yao,3 Yanbin Tan,1 ShiSheng Lin,3 Qiang Zheng,1 Zhijun Pan1 1Department of Orthopaedics, The Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang University, Hangzhou 310009, People’s Republic of China; 2Department of Emergency, The Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang University, Hangzhou 310009, People’s Republic of China; 3Department of Information Science and Electronic Engineering and State Key Laboratory of Modern Optical Instrumentation, Zhejiang University, Hangzhou 310027, People’s Republic of China *These authors contributed equally to this work Background: The osteo-immunomodulatory properties of biomaterials play an important role in the outcomes of bone regeneration. Graphene oxide (GO) has been widely applied in many research fields due to its unique properties. However, the immunomodulatory properties of GO as a biomaterial for bone tissue engineering are still unclear. Materials and methods: In this study, we evaluated the Inflammatory response of RAW264.7 cells influenced by GO. Then the osteogenic differentiation of BMSCs, and angiogenic differentiation of human umbilical vein endothelial cells (HUVECs) by stimulation with GO/RAW 264.7-conditioned culture medium were accessed. We also further investigated the possible mechanisms underlying the osteo- and angio-immunomodulatory effects of GO. Results: Our results showed that GO stimulates the secretion of oncostatin M, tumor necrosis factor alpha and other factors through the nuclear factor-κB pathway. GO/RAW264.7-conditioned medium promoted the osteogenic differentiation of BMSCs, stimulated upregulation of the HUVECs of vascular-related receptors, and promoted their tube formation in vitro. Conclusion: In conclusion, our research shows that GO, as a biomaterial, can induce the formation of a beneficial osteo-immunomodulatory environment and is a promising biomaterial for bone tissue engineering. Keywords: graphene oxide, osteo-immunomodulatory, bone marrow mesenchymal stem cells, osteogenesis, angiogenesis, RAW264.7 cells, HUVECs
