The treatment of refractory bone defects is a major clinical challenge,especially in steroid-associated osteonecrosis(SAON),which is characterized by insufficient osteogenesis and angiogenesis.Herin,a microenvironment...The treatment of refractory bone defects is a major clinical challenge,especially in steroid-associated osteonecrosis(SAON),which is characterized by insufficient osteogenesis and angiogenesis.Herin,a microenvironment responsiveness scaffold composed of poly-L-lactide(PLLA),and manganese dioxide(MnO_(2))nanoparticles is designed to enhance bone regeneration by scavenging endogenous reactive oxygen species(ROS)and modulating immune microenvironment in situ.A catalase-like catalytic reaction between MnO_(2)and endogenous hydrogen peroxide(H_(2)O_(2))generated at the bone defect area,which typically becomes acidic and ROS-rich,triggers on-demand release of oxygen and M^(n2+),significantly ameliorating inflammatory response by promoting M2-type polarization of macrophages,reprograming osteoimmune microenvironment conducive to angiogenesis and osteogenesis.Furthermore,the fundamental mechanisms were explored through transcriptome sequencing analysis,revealing that PLLA/MnO_(2)scaffolds(PMns)promote osteogenic differentiation by upre-gulating the TGF-β/Smad signaling pathway in human bone marrow mesenchymal stem cells(hBMSCs).Overall,the PMns exhibit superior immunomodulatory,excellent osteogenic-angiogenic properties and promising can-didates as bone graft substitutes for therapy clinical refractory bone defects.展开更多
基金financially supported by the National Natural Science Foundation of China(81871767)Shenzhen Medical Research Funds(B2302050)+4 种基金Guangdong Basic and Applied Basic Research Foundation(No.2022B1515120046,2023A1515010087,2023A1515011315)Shenzhen Key Laboratory of Digital Surgical Printing Project(ZDSYS201707311542415)Shenzhen Science and Technology Program(JCYJ20220818103417037,JCYJ20210324115814040,JCYJ 20210324102206016,JSGG20210629144538010,KJZD20230923115200002)Shenzhen Development and Reform Program(XMHT20220106001)the Shenzhen Basic Research General Project(JCYJ20220531100408019).
文摘The treatment of refractory bone defects is a major clinical challenge,especially in steroid-associated osteonecrosis(SAON),which is characterized by insufficient osteogenesis and angiogenesis.Herin,a microenvironment responsiveness scaffold composed of poly-L-lactide(PLLA),and manganese dioxide(MnO_(2))nanoparticles is designed to enhance bone regeneration by scavenging endogenous reactive oxygen species(ROS)and modulating immune microenvironment in situ.A catalase-like catalytic reaction between MnO_(2)and endogenous hydrogen peroxide(H_(2)O_(2))generated at the bone defect area,which typically becomes acidic and ROS-rich,triggers on-demand release of oxygen and M^(n2+),significantly ameliorating inflammatory response by promoting M2-type polarization of macrophages,reprograming osteoimmune microenvironment conducive to angiogenesis and osteogenesis.Furthermore,the fundamental mechanisms were explored through transcriptome sequencing analysis,revealing that PLLA/MnO_(2)scaffolds(PMns)promote osteogenic differentiation by upre-gulating the TGF-β/Smad signaling pathway in human bone marrow mesenchymal stem cells(hBMSCs).Overall,the PMns exhibit superior immunomodulatory,excellent osteogenic-angiogenic properties and promising can-didates as bone graft substitutes for therapy clinical refractory bone defects.
