Nano-vibration exciter:Hypoxia-inducible factor 1 signaling pathway-mediated extracellular vesicles as bioactive glass substitutes for bone regeneration  

作　　者：Zetao Wang Qiyuan Dai Huitong Luo Xiyuan Han Qi Feng Xiaodong Cao 

机构地区：[1]School of Materials Science and Engineering,South China University of Technology,Guangzhou,510641,PR China [2]National Engineering Research Centre for Tissue Restoration and Reconstruction,Guangzhou,510006,PR China [3]Key Laboratory of Biomedical Engineering of Guangdong Province,South China University of Technology,Guangzhou,510006,PR China [4]Key Laboratory of Biomedical Materials and Engineering of the Ministry of Education,South China University of Technology,Guangzhou,510006,PR China [5]Zhongshan Institute of Modern Industrial Technology of SCUT,Zhongshan,Guangdong,528437,PR China

出　　处：《Bioactive Materials》2024年第10期460-473,共14页生物活性材料（英文）

基　　金：supported by the National Key R&D Program of China(2023YFB3810200);the National Natural Science Foundation of China(Grant No.52272276,52073103,52203164);the Fundamental Research Funds for the Central Universities(No.2022ZYGXZR105);the Project funded by China Postdoctoral Science Foundation(No.2022M711183);the Science and Technology Planning Project of Guangzhou(2023A04J0971).

摘　　要：Bioactive glasses(BG)play a vital role in angiogenesis and osteogenesis through releasing functional ions.However,the rapid ion release in the early stage will cause excessive accumulation of metal ions,which in turn leads to obvious cytotoxicity,long-term inflammation,and bone repair failure.Inspired by the vibration exciter,small extracellular vesicles(sEVs)obtained by treating mesenchymal stem cells with copper-doped bioactive glass(CuBG-sEVs),is prepared as a nano-vibration exciter.The nano-vibration exciter can convert the ion signals of CuBG into biochemical factor signals through hypoxia-inducible factor 1(HIF-1)signaling pathway and its activated autophagy,so as to better exert the osteogenic activity of BG.The results showed that CuBG extracts could significantly improve the enrichment of key miRNAs and increase the yield of CuBG-sEVs by activating HIF-1 signaling pathway and its activated autophagy.Cell experiments showed that CuBG-sEVs are favor to cell recruitment,vascularization and osteogenesis as the enrichment of key miRNAs.The animal experiments results showed that CuBG-sEVs stimulated angiogenesis mediated by CD31 and promoted bone regeneration by activating signaling pathways related to osteogenesis.These findings underscored the significant potential of sEVs as alternative strategies to better roles of BG.

关 键 词：Copper-doped bioactive glass Extracellular vesicles HIF-1Α Bone regeneration 

分 类 号：R318[医药卫生—生物医学工程]