Bacterial infection is a major issue after artificial bone transplantation due to the absence of antibacterial function of bone scaffold,which seriously causes the transplant failure and even amputation in severe case...Bacterial infection is a major issue after artificial bone transplantation due to the absence of antibacterial function of bone scaffold,which seriously causes the transplant failure and even amputation in severe cases.In this study,oxygen vacancy(OV)defects Fe-doped Ti O2(OV-FeTiO2)nanoparticles were synthesized by nano TiO2and Fe3O4via high-energy ball milling,which was then incorporated into polycaprolactone/polyglycolic acid(PCLGA)biodegradable polymer matrix to construct composite bone scaffold with good antibacterial activities by selective laser sintering.The results indicated that OV defects were introduced into the core/shell-structured OV-FeTiO2nanoparticles through multiple welding and breaking during the high-energy ball milling,which facilitated the adsorption of hydrogen peroxide(H2O2)in the bacterial infection microenvironment at the bone transplant site.The accumulated H2O2could amplify the Fenton reaction efficiency to induce more hydroxyl radicals(·OH),thereby resulting in more bacterial deaths through·OH-mediated oxidative damage.This antibacterial strategy had more effective broad-spectrum antibacterial properties against Gram-negative Escherichia coli(E.coli)and Gram-positive Staphylococcus aureus(S.aureus).In addition,the PCLGA/OV-FeTiO2scaffold possessed mechanical properties that match those of human cancellous bone and good biocompatibility including cell attachment,proliferation and osteogenic differentiation.展开更多
Bacterial infection is a major problem following bone implant surgery.Moreover,poly-l-lactic acid/carbon nanotube/hydroxyapatite(PLLA/CNT/HAP)bone scaffolds possess enhanced mechanical properties and show good bioacti...Bacterial infection is a major problem following bone implant surgery.Moreover,poly-l-lactic acid/carbon nanotube/hydroxyapatite(PLLA/CNT/HAP)bone scaffolds possess enhanced mechanical properties and show good bioactiv-ityregardingbonedefectregeneration.Inthisstudy,wesynthesizedsilver(Ag)-dopedCNT/HAP(CNT/Ag-HAP)nanohybrids via the partial replacing of calcium ions(Ca2+)in the HAP lattice with silver ions(Ag+)using an ion doping technique under hydrothermal conditions.Specifically,the doping process was induced using the special lattice structure of HAP and the abundant surface oxygenic functional groups of CNT,and involved the partial replacement of Ca2+in the HAP lattice by doped Ag+as well as the in situ synthesis of Ag-HAP nanoparticles on CNT in a hydrothermal environment.The result-ing CNT/Ag-HAP nanohybrids were then introduced into a PLLA matrix via laser-based powder bed fusion(PBF-LB)to fabricate PLLA/CNT/Ag-HAP scaffolds that showed sustained antibacterial activity.We then found that Ag+,which pos-sesses broad-spectrum antibacterial activity,endowed PLLA/CNT/Ag-HAP scaffolds with this activity,with an antibacterial effectiveness of 92.65%.This antibacterial effect is due to the powerful effect of Ag+against bacterial structure and genetic material,as well as the physical destruction of bacterial structures due to the sharp edge structure of CNT.In addition,the scaffold possessed enhanced mechanical properties,showing tensile and compressive strengths of 8.49 MPa and 19.72 MPa,respectively.Finally,the scaffold also exhibited good bioactivity and cytocompatibility,including the ability to form apatite layers and to promote the adhesion and proliferation of human osteoblast-like cells(MG63 cells).展开更多
As the major cell precursors in osteogenesis, mesenchymal stem cells(MSCs) are indispensable for bone homeostasis and development. However, the primary mechanisms regulating osteogenic differentiation are controversia...As the major cell precursors in osteogenesis, mesenchymal stem cells(MSCs) are indispensable for bone homeostasis and development. However, the primary mechanisms regulating osteogenic differentiation are controversial. Composed of multiple constituent enhancers, super enhancers(SEs) are powerful cis-regulatory elements that identify genes that ensure sequential differentiation. The present study demonstrated that SEs were indispensable for MSC osteogenesis and involved in osteoporosis development. Through integrated analysis, we identified the most common SE-targeted and osteoporosis-related osteogenic gene,ZBTB16. ZBTB16, positively regulated by SEs, promoted MSC osteogenesis but was expressed at lower levels in osteoporosis.Mechanistically, SEs recruited bromodomain containing 4(BRD4) at the site of ZBTB16, which then bound to RNA polymerase IIassociated protein 2(RPAP2) that transported RNA polymerase Ⅱ(POL Ⅱ) into the nucleus. The subsequent synergistic regulation of POL Ⅱ carboxyterminal domain(CTD) phosphorylation by BRD4 and RPAP2 initiated ZBTB16 transcriptional elongation, which facilitated MSC osteogenesis via the key osteogenic transcription factor SP7. Bone-targeting ZBTB16 overexpression had a therapeutic effect on the decreased bone density and remodeling capacity of Brd4^(fl/fl)Prx1-cre mice and osteoporosis(OP) models.Therefore, our study shows that SEs orchestrate the osteogenesis of MSCs by targeting ZBTB16 expression, which provides an attractive focus and therapeutic target for osteoporosis.展开更多
基金supported by the following funds:The Natural Science Foundation of China(52275393,51935014,82072084)Hunan Provincial Natural Science Foundation of China(2021JJ20061)+4 种基金Jiangxi Provincial Natural Science Foundation of China(20224ACB204013)The Project of State Key Laboratory of Precision Manufacturing for Extreme Service PerformanceTechnology Innovation Platform Project of Shenzhen Institute of Information Technology 2020(PT2020E002)Guangdong Province Precision Manufacturing and Intelligent production education Integration Innovation Platform(2022CJPT019)Independent Exploration and Innovation Project of Central South University(1053320220553)。
文摘Bacterial infection is a major issue after artificial bone transplantation due to the absence of antibacterial function of bone scaffold,which seriously causes the transplant failure and even amputation in severe cases.In this study,oxygen vacancy(OV)defects Fe-doped Ti O2(OV-FeTiO2)nanoparticles were synthesized by nano TiO2and Fe3O4via high-energy ball milling,which was then incorporated into polycaprolactone/polyglycolic acid(PCLGA)biodegradable polymer matrix to construct composite bone scaffold with good antibacterial activities by selective laser sintering.The results indicated that OV defects were introduced into the core/shell-structured OV-FeTiO2nanoparticles through multiple welding and breaking during the high-energy ball milling,which facilitated the adsorption of hydrogen peroxide(H2O2)in the bacterial infection microenvironment at the bone transplant site.The accumulated H2O2could amplify the Fenton reaction efficiency to induce more hydroxyl radicals(·OH),thereby resulting in more bacterial deaths through·OH-mediated oxidative damage.This antibacterial strategy had more effective broad-spectrum antibacterial properties against Gram-negative Escherichia coli(E.coli)and Gram-positive Staphylococcus aureus(S.aureus).In addition,the PCLGA/OV-FeTiO2scaffold possessed mechanical properties that match those of human cancellous bone and good biocompatibility including cell attachment,proliferation and osteogenic differentiation.
基金the National Natural Science Foundation of China(Nos.52275393 and 51935014)Hunan Provincial Natural Science Foundation of China(Nos.2021JJ20061,2020JJ3047,and 2019JJ50588)+4 种基金Jiangxi Provincial Natural Science Foundation of China(No.20224ACB204013)the Project of State Key Laboratory of High Performance Complex ManufacturingTechnology Innovation Platform Project of Shenzhen Institute of Information Technology 2020(No.PT2020E002)Guangdong Province Precision Manufacturing and Intelligent Production Education Integration Innovation Platform(No.2022CJPT019)Independent Exploration and Innovation Project of Central South University(No.1053320220553).
文摘Bacterial infection is a major problem following bone implant surgery.Moreover,poly-l-lactic acid/carbon nanotube/hydroxyapatite(PLLA/CNT/HAP)bone scaffolds possess enhanced mechanical properties and show good bioactiv-ityregardingbonedefectregeneration.Inthisstudy,wesynthesizedsilver(Ag)-dopedCNT/HAP(CNT/Ag-HAP)nanohybrids via the partial replacing of calcium ions(Ca2+)in the HAP lattice with silver ions(Ag+)using an ion doping technique under hydrothermal conditions.Specifically,the doping process was induced using the special lattice structure of HAP and the abundant surface oxygenic functional groups of CNT,and involved the partial replacement of Ca2+in the HAP lattice by doped Ag+as well as the in situ synthesis of Ag-HAP nanoparticles on CNT in a hydrothermal environment.The result-ing CNT/Ag-HAP nanohybrids were then introduced into a PLLA matrix via laser-based powder bed fusion(PBF-LB)to fabricate PLLA/CNT/Ag-HAP scaffolds that showed sustained antibacterial activity.We then found that Ag+,which pos-sesses broad-spectrum antibacterial activity,endowed PLLA/CNT/Ag-HAP scaffolds with this activity,with an antibacterial effectiveness of 92.65%.This antibacterial effect is due to the powerful effect of Ag+against bacterial structure and genetic material,as well as the physical destruction of bacterial structures due to the sharp edge structure of CNT.In addition,the scaffold possessed enhanced mechanical properties,showing tensile and compressive strengths of 8.49 MPa and 19.72 MPa,respectively.Finally,the scaffold also exhibited good bioactivity and cytocompatibility,including the ability to form apatite layers and to promote the adhesion and proliferation of human osteoblast-like cells(MG63 cells).
基金supported by the National Natural Science Foundation of China [82172385 to H.S., 82172349 to Y.W.]the Key-Area Research and Development Program of Guangdong Province [2019B020236001 to H.S.]+3 种基金the Shenzhen Key Medical Discipline Construction Fund [ZDSYS20190902092851024 to H.S.]the Natural Science Foundation of Guangdong Province [2020A1515010097 to Z.X.]the Shenzhen Outstanding Science and Technology Innovation Talents-Outstanding Youth Fund project [RCYX20210706092106042 to Z.X.]Funding for open access charge:Shenzhen Key Medical Discipline Construction Fund。
文摘As the major cell precursors in osteogenesis, mesenchymal stem cells(MSCs) are indispensable for bone homeostasis and development. However, the primary mechanisms regulating osteogenic differentiation are controversial. Composed of multiple constituent enhancers, super enhancers(SEs) are powerful cis-regulatory elements that identify genes that ensure sequential differentiation. The present study demonstrated that SEs were indispensable for MSC osteogenesis and involved in osteoporosis development. Through integrated analysis, we identified the most common SE-targeted and osteoporosis-related osteogenic gene,ZBTB16. ZBTB16, positively regulated by SEs, promoted MSC osteogenesis but was expressed at lower levels in osteoporosis.Mechanistically, SEs recruited bromodomain containing 4(BRD4) at the site of ZBTB16, which then bound to RNA polymerase IIassociated protein 2(RPAP2) that transported RNA polymerase Ⅱ(POL Ⅱ) into the nucleus. The subsequent synergistic regulation of POL Ⅱ carboxyterminal domain(CTD) phosphorylation by BRD4 and RPAP2 initiated ZBTB16 transcriptional elongation, which facilitated MSC osteogenesis via the key osteogenic transcription factor SP7. Bone-targeting ZBTB16 overexpression had a therapeutic effect on the decreased bone density and remodeling capacity of Brd4^(fl/fl)Prx1-cre mice and osteoporosis(OP) models.Therefore, our study shows that SEs orchestrate the osteogenesis of MSCs by targeting ZBTB16 expression, which provides an attractive focus and therapeutic target for osteoporosis.
