Immunomodulatory properties of graphene oxide for osteogenesis and angiogenesis

Int J Nanomedicine. 2018 Sep 26:13:5799-5810. doi: 10.2147/IJN.S170305. eCollection 2018.

Abstract

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 investi gated 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: HUVECs; RAW264.7 cells; angiogenesis; bone marrow mesenchymal stem cells; graphene oxide; osteo-immunomodulatory; osteogenesis.

MeSH terms

  • Animals
  • Cell Differentiation / drug effects
  • Cell Differentiation / genetics
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Cell Survival / genetics
  • Culture Media, Conditioned / pharmacology
  • Endocytosis / drug effects
  • Gene Expression Regulation / drug effects
  • Graphite / pharmacology*
  • Human Umbilical Vein Endothelial Cells / cytology
  • Human Umbilical Vein Endothelial Cells / drug effects
  • Human Umbilical Vein Endothelial Cells / metabolism
  • Humans
  • Immunologic Factors / pharmacology*
  • Immunomodulation / drug effects
  • Inflammation / genetics
  • Inflammation / pathology
  • Macrophages / cytology
  • Macrophages / drug effects
  • Macrophages / ultrastructure
  • Mesenchymal Stem Cells / cytology
  • Mesenchymal Stem Cells / drug effects
  • Mesenchymal Stem Cells / metabolism
  • Mice
  • Neovascularization, Physiologic / drug effects*
  • Neovascularization, Physiologic / genetics
  • Osteogenesis / drug effects*
  • RAW 264.7 Cells
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Signal Transduction / drug effects

Substances

  • Culture Media, Conditioned
  • Immunologic Factors
  • RNA, Messenger
  • graphene oxide
  • Graphite