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
Porous titanium alloy is currently widely used in clinical treatment of orthopaedic diseases for its lower elastic modulus and ability to integrate with bone tissue.At the micro-level,cells can respond to different ge...Porous titanium alloy is currently widely used in clinical treatment of orthopaedic diseases for its lower elastic modulus and ability to integrate with bone tissue.At the micro-level,cells can respond to different geometries,and at the macro-level,the geometric design of implants will also affect the biological function of cells.In this study,three kinds of porous scaffolds with square,triangular and circle rod shapes were designed and 3D printed.This study observed the proliferation and differentiation of MC3T3-E1 cells during surface culture of the three types of scaffolds.It also evaluated the characteristics of the three scaffolds by means of compression tests and scanning electron microscopy to provide a reference for the design of porous titanium alloy implants for clinical applications.The trends of cell proliferation and gene expression between the three types of scaffolds were observed after treatment with two inhibitors.The results show that the square rod porous scaffolds have the best proliferative and osteogenic activities,and these findings may be due to differences in piezo-type mechanosensitive ion channel component 1(Piezo1)and Yes-associated protein(YAP)expression caused by the macro-geometric topography.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.
基金This study was carried out at the 3D Printing Innovation Research Centre of the Ninth People's Hospital Affiliated to the School of Medicine of Shanghai Jiao Tong University,and the authors thank the founding support from the Shanghai Municipal Key Clinical Specialty-Biomedical Materials(shslczdzk06701)the 3-year Action Plan of Shen kang Development Centre(SHDC2020CR2019B)+2 种基金the Huangpu District Industrial Support Fund(XK2020009)the Shanghai Engineering Research Centre of Innovative Orthopedic Instruments and Personalized Medicine(19DZ2250200)the Industry Standard Study on 3D Printing Personalized Titanium Alloy Pelvic Reconstruction Prosthesis(21DZ2201500).
文摘Porous titanium alloy is currently widely used in clinical treatment of orthopaedic diseases for its lower elastic modulus and ability to integrate with bone tissue.At the micro-level,cells can respond to different geometries,and at the macro-level,the geometric design of implants will also affect the biological function of cells.In this study,three kinds of porous scaffolds with square,triangular and circle rod shapes were designed and 3D printed.This study observed the proliferation and differentiation of MC3T3-E1 cells during surface culture of the three types of scaffolds.It also evaluated the characteristics of the three scaffolds by means of compression tests and scanning electron microscopy to provide a reference for the design of porous titanium alloy implants for clinical applications.The trends of cell proliferation and gene expression between the three types of scaffolds were observed after treatment with two inhibitors.The results show that the square rod porous scaffolds have the best proliferative and osteogenic activities,and these findings may be due to differences in piezo-type mechanosensitive ion channel component 1(Piezo1)and Yes-associated protein(YAP)expression caused by the macro-geometric topography.
