Conformationally regulated“nanozyme-like”cerium oxide with multiple free radical scavenging activities for osteoimmunology modulation and vascularized osseointegration  

作　　者：Shusen Bao Dongmei Yu Zhen Tang Hao Wu Hao Zhang Ning Wang Yichao Liu Hai Huang Chaozong Liu Xiaokang Li Zheng Guo 

机构地区：[1]Department of Orthopedics,Tangdu Hospital,Fourth Military Medical University,Xi’an,710038,China [2]University College London,UCL Institute of Orthopaedics and Musculo-Skeletal Science,M14 the Royal National Orthopaedic Hospital,Stanmore,HA74LP,United Kingdom [3]Department of Orthopedics,No.903 Hospital of PLA Joint Logistic Support Force,Hangzhou,310000,China [4]Department of Burn Surgery,Xijing Hospital,Fourth Military Medical University,Xi’an,710038,China

出　　处：《Bioactive Materials》2024年第4期64-79,共16页生物活性材料（英文）

基　　金：supported by grants from the National Key Research and Development Program of China(grant number 2017YFC1104900);the National Natural Science Foundation of China(No.82372124,51871239,and 51771227);the support from the Incubation Program of China Army Medical Science and Technology Youth Training Program(No.17QNP021);the Everest Program of Air Force Military Medical University(No.2020ZFC002)。

摘　　要：Given post-operative aseptic loosening in orthopedic disease treatment,osteointegration occurs at the bone-implant interface as a holistic process,including immunoregulation(e.g.,macrophage polarization),angiogenesis and osteogenesis in sequence.In order to achieve early rapid and satisfactory osseointegration,different nano-shaped(nanocone,nanopolyhedron and nanoflower abbr.NC,NP&NF)cerium oxide(CeO_(2-x))coatings,endowed with“nanozyme-like”activities for multiple free radical elimination and osteoimmunology regulation,were hydrothermally synthesized on titanium alloy(TC4).In vitro cell experiments showed that nano-CeO_(2-x) coated TC4 not only induced polarization of RAW264.7 cells toward M2 phenotype,but also promoted angiogenesis and vascularization of endothelial cells along with differentiation and mineralization of osteogenic precursor cells.Improvements in M2-polarized macrophage,angiogenesis,and bone regeneration were further confirmed in a rat femoral condyle model.Among the above three nano-morphologies,NF exhibited the best osseoinetegration.RNA sequencing and mechanism exploration suggested that the inhibition of PI3K-AKT signaling pathway was essential for immunomodulatory capacity of NF.In conclusion,it provided promising insights into the immunomodulatory exploitation of orthopedic implants.

关 键 词：“Nanozyme-like”cerium oxide Durable redox activation Free radical scavenging Osteoimmunology modulation Vascularized osseointegration 

分 类 号：R68[医药卫生—骨科学]