The key to managing fracture is to achieve stable internal fixation,and currently,biologically and mechanically appropriate internal fixation devices are urgently needed.With excellent biocompatibility and corrosion r...The key to managing fracture is to achieve stable internal fixation,and currently,biologically and mechanically appropriate internal fixation devices are urgently needed.With excellent biocompatibility and corrosion resistance,titanium–niobium alloys have the potential to become a new generation of internal fixation materials for fractures.However,the role and mechanism of titanium–niobium alloys on promoting fracture healing are still undefined.Therefore,in this study,we systematically evaluated the bone-enabling properties of Ti45Nb via in vivo and in vitro experiments.In vitro,we found that Ti45Nb has an excellent ability to promote MC3T3-E1 cell adhesion and proliferation without obvious cytotoxicity.Alkaline phosphatase(ALP)activity and alizarin red staining and semiquantitative analysis showed that Ti45Nb enhanced the osteogenic differentiation of MC3T3-E1 cells compared to the Ti6Al4V control.In the polymerase chain reaction experiment,the expression of osteogenic genes in the Ti45Nb group,such as ALP,osteopontin(OPN),osteocalcin(OCN),type 1 collagen(Col-1)and runt-related transcription factor-2(Runx2),was significantly higher than that in the control group.Meanwhile,in the western blot experiment,the expression of osteogenic-related proteins in the Ti45Nb group was significantly increased,and the expression of PI3K–Akt-related proteins was also higher,which indicated that Ti45Nb might promote fracture healing by activating the PI3K–Akt signaling pathway.In vivo,we found that Ti45Nb implants accelerated fracture healing compared to Ti6Al4V,and the biosafety of Ti45Nb was confirmed by histological evaluation.Furthermore,immunohistochemical staining confirmed that Ti45Nb may promote osteogenesis by upregulating the PI3K/Akt signaling pathway.Our study demonstrated that Ti45Nb exerts an excellent ability to promote fracture healing as well as enhance osteoblast differentiation by activating the PI3K/Akt signaling pathway,and its good biosafety has been confirmed,which indicates its clinical translation potential.展开更多
To solve the problems of low precision of weak feature extraction,heavy reliance on labor and low efficiency of weak feature extraction in X-ray weld detection image of ultra-high voltage(UHV)equipment key parts,an au...To solve the problems of low precision of weak feature extraction,heavy reliance on labor and low efficiency of weak feature extraction in X-ray weld detection image of ultra-high voltage(UHV)equipment key parts,an automatic feature extraction algorithm is proposed.Firstly,the original weld image is denoised while retaining the characteristic information of weak defects by the proposed monostable stochastic resonance method.Then,binarization is achieved by combining Laplacian edge detection and Otsu threshold segmentation.Finally,the automatic identification of weld defect area is realized based on the sequential traversal of binary tree.Several characteristic analysis dimensions are established for weld defects of UHV key parts,including defect area,perimeter,slenderness ratio,duty cycle,etc.The experiment using theweld detection image of the actual production site shows that the proposedmethod can effectively extract theweak feature information ofweld defects and further provide reference for decision-making.展开更多
Complicated and large acetabular bone defects present the main challenges and difficulty in the revision of total hip arthroplasty(THA).This study aimed to explore the advantages of three-dimensional(3D)printing techn...Complicated and large acetabular bone defects present the main challenges and difficulty in the revision of total hip arthroplasty(THA).This study aimed to explore the advantages of three-dimensional(3D)printing technology in the reconstruction of such acetabular bone defects.We retrospectively analyzed the prognosis of four severe bone defects around the acetabulum in three patients who were treated using 3D printing technology.Reconstruction of bone defect by conventional methods was difficult in these patients.In this endeavor,we used radiographic methods,related computer software such as Materialise's interactive medical image control system and Siemens NX software,and actual surgical experience to estimate defect volume,prosthesis stability,and installation accuracy,respectively.Moreover,a Harris hip score was obtained to evaluate limb function.It was found that bone defects could be adequately reconstructed using a 3D printing prosthesis,and its stability was reliable.The Harris hip score indicated a very good functional recovery in all three patients.In conclusion,3D printing technology had a good therapeutic effect on both complex and large bone defects in the revision of THA.It was able to achieve good curative effects in patients with large bone defects.展开更多
Glycine max L.accumulates a large amount of isoflavonoid compounds,which is beneficial for plant defense,plant-microbe symbiotic interactions,and human health.Several CYP450 subfamily genes are involved in the flavono...Glycine max L.accumulates a large amount of isoflavonoid compounds,which is beneficial for plant defense,plant-microbe symbiotic interactions,and human health.Several CYP450 subfamily genes are involved in the flavonoid biosynthetic pathway in plants.In the present study,we found 24 CYP82 subfamily genes were differentially expressed in various tissues of soybean,in Phytophthora sojae-infected soybean varieties and in soybean hairy roots treated with cell wall glucan elicitor.Six of them(GmCYP82A2,GmCYP82A3,GmCYP82A4,GmCYP82A23,GmCYP82C20 and GmCYP82D26)were co-expressed with other known isoflavonoid pathway genes in soybean.Their enzymatic activity in yeast feeding assays showed that only GmCYP82D26 was able to convert naringenin to daidzein with both aryl migration and dehydration function.When GmCYP82D26 was over-expressed in soybean hairy roots,the contents of the two major isoflavonoid aglycones in soybean(daidzein and genistein)were reduced,but total flavonoids were not affected.When GmCYP82D26 was suppressed by RNAi in the hairy roots,daidzein content was decreased but genistein content was increased,with unchanged total flavonoid content.GmCYP82D26 was found to be localized in the endoplasmic reticulum at subcellular level when transiently expressed in tobacco leaf epidermis.GmCYP82D26 gene was preferentially expressed in roots,with low expression level in other tissues in soybean.Homology modeling and molecular docking showed that GmCYP82D26 could form hydrogen bond with both HEM and naringenin at C5-OH and C4 carbonyl.All these results indicated that GmCYP82D26 possesses new and dual enzymatic activity,which bridges the two branches(daidzein and genistein branch)of isoflavonoid pathway in soybean.展开更多
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
Regeneration of Intervertebral disc(IVD)is a scientific challenge because of the complex structure and composition of tissue,as well as the difficulty in achieving bionic function.Here,an anatomically correct IVD scaf...Regeneration of Intervertebral disc(IVD)is a scientific challenge because of the complex structure and composition of tissue,as well as the difficulty in achieving bionic function.Here,an anatomically correct IVD scaffold composed of biomaterials,cells,and growth factors were fabricated via three-dimensional(3D)bioprinting technology.Connective tissue growth factor(CTGF)and transforming growth factor-β3(TGF-β3)were loaded onto polydopamine nanoparticles,which were mixed with bone marrow mesenchymal stem cells(BMSCs)for regenerating and simulating the structure and function of the nucleus pulposus and annular fibrosus.In vitro experiments confirmed that CTGF and TGF-β3 could be released from the IVD scaffold in a spatially controlled manner,and induced the corresponding BMSCs to differentiate into nucleus pulposus like cells and annulus fibrosus like cells.Next,the fabricated IVD scaffold was implanted into the dorsum subcutaneous of nude mice.The reconstructed IVD exhibited a zone-specific matrix that displayed the corresponding histological and immunological phenotypes:primarily type II collagen and glycosaminoglycan in the core zone,and type I collagen in the surrounding zone.The testing results demonstrated that it exhibited good biomechanical function of the reconstructed IVD.The results presented herein reveal the clinical application potential of the dual growth factors-releasing IVD scaffold fabricated via 3D bioprinting.However,the evaluation in large mammal animal models needs to be further studied.展开更多
Dear Editor,Human cell-based and personalized in vitro cartilage models are urgently needed for osteoarthritis treatment in pre-clinical regenerative medicine development.Cellular self-assemblies and condensations of ...Dear Editor,Human cell-based and personalized in vitro cartilage models are urgently needed for osteoarthritis treatment in pre-clinical regenerative medicine development.Cellular self-assemblies and condensations of the appropriate stem cells could initiate the formation of transient tissue structures programmed for specific organogenesis processes.1 This recapitulation of developmental events has previously been demonstrated for the formation of cardiac,epithelial and liver organoids.However,there has been very limited progress in the development of human cartilage organoids for osteoarthritis(OA).2 Here,we describe the fabrication of functional bioengineered cartilage organoid suitable for OA treatment.Briefly,agarose microwell inserts for formation of a high number of synovial mesenchymal stromal cell(SMSC)organoids with homogeneous size distribution were created as previously described by Leijten et al.33D-cultured SMSC organoids were generated and phenotypically analyzed for potential applications in OA modeling and treatment(Fig.1a).展开更多
基金This work was supported by the National Natural Science Foundation of China(Nos.81972058,81902194 and 82202680)the Science and Technology Commission of Shanghai Municipality(No.22YF1422900)+3 种基金the Shanghai Municipal Key Clinical Specialty,China(No.shslczdzk06701)the National Facility for Translational Medicine(Shanghai),China(No.TMSZ-2020-207)the Shanghai Engineering Research Center of Orthopedic Innovative Instruments and Personalized Medicine Instruments and Personalized Medicine(No.19DZ2250200)the Key R&D Program of Ningxia,China(Nos.2020BCH01001 and 2021BEG02037).
文摘The key to managing fracture is to achieve stable internal fixation,and currently,biologically and mechanically appropriate internal fixation devices are urgently needed.With excellent biocompatibility and corrosion resistance,titanium–niobium alloys have the potential to become a new generation of internal fixation materials for fractures.However,the role and mechanism of titanium–niobium alloys on promoting fracture healing are still undefined.Therefore,in this study,we systematically evaluated the bone-enabling properties of Ti45Nb via in vivo and in vitro experiments.In vitro,we found that Ti45Nb has an excellent ability to promote MC3T3-E1 cell adhesion and proliferation without obvious cytotoxicity.Alkaline phosphatase(ALP)activity and alizarin red staining and semiquantitative analysis showed that Ti45Nb enhanced the osteogenic differentiation of MC3T3-E1 cells compared to the Ti6Al4V control.In the polymerase chain reaction experiment,the expression of osteogenic genes in the Ti45Nb group,such as ALP,osteopontin(OPN),osteocalcin(OCN),type 1 collagen(Col-1)and runt-related transcription factor-2(Runx2),was significantly higher than that in the control group.Meanwhile,in the western blot experiment,the expression of osteogenic-related proteins in the Ti45Nb group was significantly increased,and the expression of PI3K–Akt-related proteins was also higher,which indicated that Ti45Nb might promote fracture healing by activating the PI3K–Akt signaling pathway.In vivo,we found that Ti45Nb implants accelerated fracture healing compared to Ti6Al4V,and the biosafety of Ti45Nb was confirmed by histological evaluation.Furthermore,immunohistochemical staining confirmed that Ti45Nb may promote osteogenesis by upregulating the PI3K/Akt signaling pathway.Our study demonstrated that Ti45Nb exerts an excellent ability to promote fracture healing as well as enhance osteoblast differentiation by activating the PI3K/Akt signaling pathway,and its good biosafety has been confirmed,which indicates its clinical translation potential.
文摘To solve the problems of low precision of weak feature extraction,heavy reliance on labor and low efficiency of weak feature extraction in X-ray weld detection image of ultra-high voltage(UHV)equipment key parts,an automatic feature extraction algorithm is proposed.Firstly,the original weld image is denoised while retaining the characteristic information of weak defects by the proposed monostable stochastic resonance method.Then,binarization is achieved by combining Laplacian edge detection and Otsu threshold segmentation.Finally,the automatic identification of weld defect area is realized based on the sequential traversal of binary tree.Several characteristic analysis dimensions are established for weld defects of UHV key parts,including defect area,perimeter,slenderness ratio,duty cycle,etc.The experiment using theweld detection image of the actual production site shows that the proposedmethod can effectively extract theweak feature information ofweld defects and further provide reference for decision-making.
基金This work is supported by National Key Research and Development Program of China(2016YFC1100600)the National Natural Science Foundation of China(81972058 and 81902194)the Multicenter Clinical Research Project of Shanghai Jiao Tong University School of Medicine(DLY201506).
文摘Complicated and large acetabular bone defects present the main challenges and difficulty in the revision of total hip arthroplasty(THA).This study aimed to explore the advantages of three-dimensional(3D)printing technology in the reconstruction of such acetabular bone defects.We retrospectively analyzed the prognosis of four severe bone defects around the acetabulum in three patients who were treated using 3D printing technology.Reconstruction of bone defect by conventional methods was difficult in these patients.In this endeavor,we used radiographic methods,related computer software such as Materialise's interactive medical image control system and Siemens NX software,and actual surgical experience to estimate defect volume,prosthesis stability,and installation accuracy,respectively.Moreover,a Harris hip score was obtained to evaluate limb function.It was found that bone defects could be adequately reconstructed using a 3D printing prosthesis,and its stability was reliable.The Harris hip score indicated a very good functional recovery in all three patients.In conclusion,3D printing technology had a good therapeutic effect on both complex and large bone defects in the revision of THA.It was able to achieve good curative effects in patients with large bone defects.
基金supported by the Agricultural Science and Technology Innovation Program (ASTIP-IAS10).
文摘Glycine max L.accumulates a large amount of isoflavonoid compounds,which is beneficial for plant defense,plant-microbe symbiotic interactions,and human health.Several CYP450 subfamily genes are involved in the flavonoid biosynthetic pathway in plants.In the present study,we found 24 CYP82 subfamily genes were differentially expressed in various tissues of soybean,in Phytophthora sojae-infected soybean varieties and in soybean hairy roots treated with cell wall glucan elicitor.Six of them(GmCYP82A2,GmCYP82A3,GmCYP82A4,GmCYP82A23,GmCYP82C20 and GmCYP82D26)were co-expressed with other known isoflavonoid pathway genes in soybean.Their enzymatic activity in yeast feeding assays showed that only GmCYP82D26 was able to convert naringenin to daidzein with both aryl migration and dehydration function.When GmCYP82D26 was over-expressed in soybean hairy roots,the contents of the two major isoflavonoid aglycones in soybean(daidzein and genistein)were reduced,but total flavonoids were not affected.When GmCYP82D26 was suppressed by RNAi in the hairy roots,daidzein content was decreased but genistein content was increased,with unchanged total flavonoid content.GmCYP82D26 was found to be localized in the endoplasmic reticulum at subcellular level when transiently expressed in tobacco leaf epidermis.GmCYP82D26 gene was preferentially expressed in roots,with low expression level in other tissues in soybean.Homology modeling and molecular docking showed that GmCYP82D26 could form hydrogen bond with both HEM and naringenin at C5-OH and C4 carbonyl.All these results indicated that GmCYP82D26 possesses new and dual enzymatic activity,which bridges the two branches(daidzein and genistein branch)of isoflavonoid pathway in soybean.
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 National Key R&D Program of China(No.2018YFB1105600,No.2018YFA0703000)National Natural Science Foundation of China(No.81802131)Project funded by China Postdoctoral Science Foundation(No.2019T120347)and the fund of No.XK2019013.
文摘Regeneration of Intervertebral disc(IVD)is a scientific challenge because of the complex structure and composition of tissue,as well as the difficulty in achieving bionic function.Here,an anatomically correct IVD scaffold composed of biomaterials,cells,and growth factors were fabricated via three-dimensional(3D)bioprinting technology.Connective tissue growth factor(CTGF)and transforming growth factor-β3(TGF-β3)were loaded onto polydopamine nanoparticles,which were mixed with bone marrow mesenchymal stem cells(BMSCs)for regenerating and simulating the structure and function of the nucleus pulposus and annular fibrosus.In vitro experiments confirmed that CTGF and TGF-β3 could be released from the IVD scaffold in a spatially controlled manner,and induced the corresponding BMSCs to differentiate into nucleus pulposus like cells and annulus fibrosus like cells.Next,the fabricated IVD scaffold was implanted into the dorsum subcutaneous of nude mice.The reconstructed IVD exhibited a zone-specific matrix that displayed the corresponding histological and immunological phenotypes:primarily type II collagen and glycosaminoglycan in the core zone,and type I collagen in the surrounding zone.The testing results demonstrated that it exhibited good biomechanical function of the reconstructed IVD.The results presented herein reveal the clinical application potential of the dual growth factors-releasing IVD scaffold fabricated via 3D bioprinting.However,the evaluation in large mammal animal models needs to be further studied.
基金This work was funded by the National Key R&D Program of China(No.2018YFB1105600,No.2018YFA0703000)China National Natural Science Funds(No.51631009,No.81802122)+1 种基金Chinese post-doctoral funding(No.2019M661559)the Funds from Shanghai jiao tong university for the Clinical and Translational Research Center for 3D Printing Technology.
文摘Dear Editor,Human cell-based and personalized in vitro cartilage models are urgently needed for osteoarthritis treatment in pre-clinical regenerative medicine development.Cellular self-assemblies and condensations of the appropriate stem cells could initiate the formation of transient tissue structures programmed for specific organogenesis processes.1 This recapitulation of developmental events has previously been demonstrated for the formation of cardiac,epithelial and liver organoids.However,there has been very limited progress in the development of human cartilage organoids for osteoarthritis(OA).2 Here,we describe the fabrication of functional bioengineered cartilage organoid suitable for OA treatment.Briefly,agarose microwell inserts for formation of a high number of synovial mesenchymal stromal cell(SMSC)organoids with homogeneous size distribution were created as previously described by Leijten et al.33D-cultured SMSC organoids were generated and phenotypically analyzed for potential applications in OA modeling and treatment(Fig.1a).
