Magnesium(Mg)alloys that have both antibacterial and osteogenic properties are suitable candidates for orthopedic implants.However,the fabrication of ideal Mg implants suitable for bone repair remains challenging beca...Magnesium(Mg)alloys that have both antibacterial and osteogenic properties are suitable candidates for orthopedic implants.However,the fabrication of ideal Mg implants suitable for bone repair remains challenging because it requires implants with interconnected pore structures and personalized geometric shapes.In this study,we fabricated a porous 3D-printed Mg-Nd-Zn-Zr(denoted as JDBM)implant with suitable mechanical properties using selective laser melting technology.The 3D-printed JDBM implant exhibited cytocompatibility in MC3T3-E1 and RAW267.4 cells and excellent osteoinductivity in vitro.Furthermore,the implant demonstrated excellent antibacterial ratios of 90.0% and 92.1% for methicillin-resistant S.aureus(MRSA)and Escherichia coli,respectively.The 3D-printed JDBM implant prevented MRSA-induced implant-related infection in a rabbit model and showed good in vivo biocompatibility based on the results of histological evaluation,blood tests,and Mg2+deposition detection.In addition,enhanced inflammatory response and TNF-α secretion were observed at the bone-implant interface of the 3D-printed JDBM implants during the early implantation stage.The high Mg^(2+)environment produced by the degradation of 3D-printed JDBM implants could promote M1 phenotype of macrophages(Tnf,iNOS,Ccl3,Ccl4,Ccl5,Cxcl10,and Cxcl2),and enhance the phagocytic ability of macrophages.The enhanced immunoregulatory effect generated by relatively fast Mg^(2+)release and implant degradation during the early implantation stage is a potential antibacterial mechanism of Mg-based implant.Our findings indicate that 3D-printed porous JDBM implants,having both antibacterial property and osteoinductivity,hold potential for future orthopedic applications.展开更多
Repetitive implant-related infections(IRIs)are devastating complications in orthopedic surgery,threatening implant survival and even the life of the host.Biofilms conceal bacterial-associated antigens(BAAs)and result ...Repetitive implant-related infections(IRIs)are devastating complications in orthopedic surgery,threatening implant survival and even the life of the host.Biofilms conceal bacterial-associated antigens(BAAs)and result in a"cold tumor"-like immune silent microenvironment,allowing the persistence of IRIs.To address this challenge,an iron-based covalent organic framed nanoadjuvant doped with curcumin and platinum(CFCP)was designed in the present study to achieve efficient treatment of IRIs by inducing a systemic immune response.Specifically,enhanced sonodynamic therapy(SDT)from CFCP combined with iron ion metabolic interference increased the release of bacterial-associated double-stranded DNA(dsDNA).Immunogenic dsDNA promoted dendritic cell(DC)maturation through activation of the stimulator of interferon gene(STING)and amplified the immune stimulation of neutrophils via interferon-β(IFN-β).At the same time,enhanced BAA presentation aroused humoral immunity in B and T cells,creating long-term resistance to repetitive infections.Encouragingly,CFCP served as neoadjuvant immunotherapy for sustained antibacterial protection on implants and was expected to guide clinical IRI treatment and relapse prevention.展开更多
基金supported by the National Natural Science Foundation of China(81972058,81902194,81902201,and 51821001)National Key R&D Program of China(2016YFC1100600,subproject 2016YFC1100604)+4 种基金Multicenter Clinical Research Project of Shanghai Jiao Tong University School of Medicine,China(DLY201506)High Technology and Key Development Project of Ningbo,China(2019B10102)Shanghai Municipal Key Clinical Specialty,China(shslczdzk06701)National Facility for Translational Medicine(Shanghai),China(TMSZ-2020-207)the Interdisciplinary Program of Shanghai Jiao Tong University,China(YG2019QN2019).
文摘Magnesium(Mg)alloys that have both antibacterial and osteogenic properties are suitable candidates for orthopedic implants.However,the fabrication of ideal Mg implants suitable for bone repair remains challenging because it requires implants with interconnected pore structures and personalized geometric shapes.In this study,we fabricated a porous 3D-printed Mg-Nd-Zn-Zr(denoted as JDBM)implant with suitable mechanical properties using selective laser melting technology.The 3D-printed JDBM implant exhibited cytocompatibility in MC3T3-E1 and RAW267.4 cells and excellent osteoinductivity in vitro.Furthermore,the implant demonstrated excellent antibacterial ratios of 90.0% and 92.1% for methicillin-resistant S.aureus(MRSA)and Escherichia coli,respectively.The 3D-printed JDBM implant prevented MRSA-induced implant-related infection in a rabbit model and showed good in vivo biocompatibility based on the results of histological evaluation,blood tests,and Mg2+deposition detection.In addition,enhanced inflammatory response and TNF-α secretion were observed at the bone-implant interface of the 3D-printed JDBM implants during the early implantation stage.The high Mg^(2+)environment produced by the degradation of 3D-printed JDBM implants could promote M1 phenotype of macrophages(Tnf,iNOS,Ccl3,Ccl4,Ccl5,Cxcl10,and Cxcl2),and enhance the phagocytic ability of macrophages.The enhanced immunoregulatory effect generated by relatively fast Mg^(2+)release and implant degradation during the early implantation stage is a potential antibacterial mechanism of Mg-based implant.Our findings indicate that 3D-printed porous JDBM implants,having both antibacterial property and osteoinductivity,hold potential for future orthopedic applications.
基金supported by the National Natural Science Foundation of China(82272512,82102586)the Natural Science Foundation of Anhui Province,Distinguishing Youth Project(2108085J40)+1 种基金Anhui Provincial Scientific Research Compilation Project(2022AH051251,2022AH010076)Research Funds of Centre for Leading Medicine and Advanced Technologies of IHM(2023IHM01070,2023IHM01074).
文摘Repetitive implant-related infections(IRIs)are devastating complications in orthopedic surgery,threatening implant survival and even the life of the host.Biofilms conceal bacterial-associated antigens(BAAs)and result in a"cold tumor"-like immune silent microenvironment,allowing the persistence of IRIs.To address this challenge,an iron-based covalent organic framed nanoadjuvant doped with curcumin and platinum(CFCP)was designed in the present study to achieve efficient treatment of IRIs by inducing a systemic immune response.Specifically,enhanced sonodynamic therapy(SDT)from CFCP combined with iron ion metabolic interference increased the release of bacterial-associated double-stranded DNA(dsDNA).Immunogenic dsDNA promoted dendritic cell(DC)maturation through activation of the stimulator of interferon gene(STING)and amplified the immune stimulation of neutrophils via interferon-β(IFN-β).At the same time,enhanced BAA presentation aroused humoral immunity in B and T cells,creating long-term resistance to repetitive infections.Encouragingly,CFCP served as neoadjuvant immunotherapy for sustained antibacterial protection on implants and was expected to guide clinical IRI treatment and relapse prevention.
