Interactions between bone cells and neurocytes are crucial for endosseous nerve and ensuing bone regeneration.However,absence of neural stem cells in bone makes the innervation of implant osseointegration a major chal...Interactions between bone cells and neurocytes are crucial for endosseous nerve and ensuing bone regeneration.However,absence of neural stem cells in bone makes the innervation of implant osseointegration a major challenge.Herein,a nanorod-like array of sodium hydrogen titanate(ST)co-doped with Co^(2+)and Co^(3+),namely STC_(h) that behaves as a reactive oxygen species(ROS)-scavenging enzyme,was hydrothermally formed on Ti substrate.We show that the doped Co^(2+)and Co^(3+)locate at TiO_(6) octahedral interlayers and within octahedra of STC_(h) lattice,appearing releasable and un-releasable,respectively,leading to an increase in Co^(3+)/Co^(2+)ratio and enzyme activity of the array with immersion.The nanoenzyme-released Co^(2+)triggers macrophages(Ms)towards M1 phenotype,then the nanoenzyme scavenges extracellular ROS inducing M1-to-M2 transition.The neurogenic factors secreted by STC_(h)-regulated MΦs,in combination with the released Co^(2+),promote mesenchymal stem cells to differentiate into neurons and Schwann cells compared to sole Co^(2+)and sT.STC_(h) array greatly enhances nerve reconstruction,type-H capillary formation and ensuing osseointegration in normal rat bone,and antibacteria via engulfing S.aureus by MΦs and osteogenesis in infective case.This nanoenzyme provides an alternative strategy to orchestrate endosseous nerve regeneration for osseointegration without loading exogenous neurotrophins in implants.展开更多
基金the National Key Research and Development Program of China(Grant No.2023YFC2412600)National Natural Science Foundation of China(Grant No.51971171).
文摘Interactions between bone cells and neurocytes are crucial for endosseous nerve and ensuing bone regeneration.However,absence of neural stem cells in bone makes the innervation of implant osseointegration a major challenge.Herein,a nanorod-like array of sodium hydrogen titanate(ST)co-doped with Co^(2+)and Co^(3+),namely STC_(h) that behaves as a reactive oxygen species(ROS)-scavenging enzyme,was hydrothermally formed on Ti substrate.We show that the doped Co^(2+)and Co^(3+)locate at TiO_(6) octahedral interlayers and within octahedra of STC_(h) lattice,appearing releasable and un-releasable,respectively,leading to an increase in Co^(3+)/Co^(2+)ratio and enzyme activity of the array with immersion.The nanoenzyme-released Co^(2+)triggers macrophages(Ms)towards M1 phenotype,then the nanoenzyme scavenges extracellular ROS inducing M1-to-M2 transition.The neurogenic factors secreted by STC_(h)-regulated MΦs,in combination with the released Co^(2+),promote mesenchymal stem cells to differentiate into neurons and Schwann cells compared to sole Co^(2+)and sT.STC_(h) array greatly enhances nerve reconstruction,type-H capillary formation and ensuing osseointegration in normal rat bone,and antibacteria via engulfing S.aureus by MΦs and osteogenesis in infective case.This nanoenzyme provides an alternative strategy to orchestrate endosseous nerve regeneration for osseointegration without loading exogenous neurotrophins in implants.
