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Electrochemically derived nanographene oxide activates endothelial tip cells and promotes angiogenesis by binding endogenous lysophosphatidic acid

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Bioactive Materials 2022年第3期7卷 92-104页

作者： Wenjing Liu Haiyun Luo Qinwei Wei Jia Liu Junrong Wu Yanli Zhang Lili Chen Wencai Ren Longquan Shao Stomatological Hospital Southern Medical UniversityGuangzhou510280China Guangdong Provincial Key Laboratory of Construction and Detection in Tissue Engineering Guangzhou510515China Shenyang National Laboratory for Materials Science Institute of Metal ResearchChinese Academy of SciencesShenyang110016China Stomatology Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan430022China

Graphene oxide(GO)exhibits good mechanical and physicochemical characteristics and has extensive application prospects in bone tissue engineering.However,its effect on angiogenesis is unclear,and its potential toxic effects are heavily disputed.Herein,we found that nanographene oxide(NGO)synthesized by one-step water electrolytic oxidation is smaller and shows superior biocompatibility.Moreover,NGO significantly enhanced angiogenesis in calvarial bone defect areas in vivo,providing a good microenvironment for bone regeneration.Endothelial tip cell differentiation is an important step in the initiation of angiogenesis.We verified that NGO activates endothelial tip cells by coupling with lysophosphatidic acid(LPA)in serum via strong hydrogen bonding interactions,which has not been reported.In addition,the mechanism by which NGO promotes angiogenesis was systematically studied.NGO-coupled LPA activates LPAR6 and facilitates the formation of migratory tip cells via hippo/Yes-associated protein(YAP)independent of reactive oxygen species(ROS)stimulation or additional complex modifications.These results provide an effective strategy for the application of electrochemically derived NGO and more insight into NGO-mediated angiogenesis.

关键词： Nanographene oxide Lysophosphatidic acid Hydrogen bonding Endothelial tip cell Hippo signalling

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