Magnesium(Mg)and its alloys as temporary medical implants with biodegradable and properly mechanical properties have been investigated for a long time.There are already three kinds of biodegradable Mg implants which a...Magnesium(Mg)and its alloys as temporary medical implants with biodegradable and properly mechanical properties have been investigated for a long time.There are already three kinds of biodegradable Mg implants which are approved by Conformite Europeene(CE)or Korea Food and Drug Administration(KFDA),but not China Food and Drug Administration(CFDA,now it is National Medical Products Administration,NMPA).As we know,Chinese researchers,surgeons,and entrepreneurs have tried a lot to research and develop biodegradable Mg implants which might become other new approved implants for clinical applications.So in this review,we present the representative Mg implants of three categories,orthopedic implants,surgical implants,and intervention implants and provide an overview of current achievement in China from academic publications and Chinese patents.We would like to provide a systematic way to translate Mg and its alloy implants from experiment designs to clinical products.展开更多
Tantalum exhibits excellent biocompatibility and good chemical stability, which has been employed in dental and orthopedic applications.The local microenvironment of the surface of implants influence determines the su...Tantalum exhibits excellent biocompatibility and good chemical stability, which has been employed in dental and orthopedic applications.The local microenvironment of the surface of implants influence determines the surrounding cell responses.In this work, nano-dimpled structure on the surface of pure tantalum was fabricated by electrochemical anodization.The surface morphology of the nano-dimpled structure was observed, and the dimensions of the nano-dimpled structure were measured by scanning electron microscopy(SEM).The surface roughness of the sample with nano-dimpled structure was measured by atomic force microscopy(AFM).The results show that the diameter of nano-dimpled ranges from 40 to 180 nm, and the higher the applied voltage, the larger the diameter.Moreover, nano-dimpled structure has good hydrophilicity.In vitro results show that nano-dimpled structure can promote the adhesion and proliferation of mouse cranial anterior bone(MC-3T3-E1) cells.The filopodia of MC-3T3-E1 cells can be fully extended on this nano-dimpled structure.On the surface of the nano-dimpled structure with a dimple size of 40 nm, the cells have the longest aspect ratio.The small dimple size of the nanodimpled structure is beneficial to cell proliferation and osteogenic differentiation.展开更多
Relapse and metastasis of tumor may occur for osteosarcoma(OS)patients after clinical resection.Conventional metallic scaffolds provide sufficient mechanical support to the defected bone but fail to eradicate recurrin...Relapse and metastasis of tumor may occur for osteosarcoma(OS)patients after clinical resection.Conventional metallic scaffolds provide sufficient mechanical support to the defected bone but fail to eradicate recurring tumors.Here we report that biodegradable magnesium(Mg)wirebased implant can inhibit OS growth.In brief,the Mg wires release Mg ions to activate the transport of zinc finger protein Snail1 from cytoplasm to cell nucleus,which induces apoptosis and inhibits proliferation of OS cells through a parallel antitumor signaling pathway of miRNA-181d-5p/TIMP3 and miRNA-181c-5p/NLK downstream.Simultaneously,the hydrogen gas evolution from Mg wires eliminates intracellular excessive reactive oxygen species,by which the growth of bone tumor cells is suppressed.The subcutaneous tumor-bearing experiment of OS cells in nude mice further confirms that Mg wires can effectively inhibit the growth of tumors and prolong the survival of tumor-bearing mice.In addition,Mg wires have no toxicity to normal cells and tissues.These results suggest that Mg implant is a potential anti-tumor scaffold for OS patients.展开更多
Hydrogen has been used to suppress tumor growth with considerable efficacy.Inhalation of hydrogen gas and oral ingestion of hydrogen-rich saline are two common systemic routes of hydrogen administration.We have develo...Hydrogen has been used to suppress tumor growth with considerable efficacy.Inhalation of hydrogen gas and oral ingestion of hydrogen-rich saline are two common systemic routes of hydrogen administration.We have developed a topical delivery method of hydrogen at targeted sites through the degradation of magnesium-based biomaterials.However,the underlying mechanism of hydrogen’s role in cancer treatment remains ambiguous.Here,we investigate the mechanism of tumor cell apoptosis triggered by the hydrogen released from magnesium-based biomaterials.We find that the localized release of hydrogen increases the expression level of P53 tumor suppressor proteins,as demonstrated by the in vitro RNA sequencing and protein expression analysis.Then,the P53 proteins disrupt the membrane potential of mitochondria,activate autophagy,suppress the reactive oxygen species in cancer cells,and finally result in tumor suppression.The anti-tumor efficacy of magnesium-based biomaterials is further validated in vivo by inserting magnesium wire into the subcutaneous tumor in a mouse.We also discovered that the minimal hydrogen concentration from magnesium wires to trigger substantial tumor apoptosis is 91.2μL/mm^(3)per day,which is much lower than that required for hydrogen inhalation.Taken together,these findings reveal the release of H2 from magnesium-based biomaterial exerts its anti-tumoral activity by activating the P53-mediated lysosome-mitochondria apoptosis signaling pathway,which strengthens the therapeutic potential of this biomaterial as localized anti-tumor treatment.展开更多
Lean alloy(low alloyed)is beneficial for long-term sustainable development of metal materials.Creating a nanocrystalline microstructure is a desirable approach to improve biodegradability and mechanical properties of ...Lean alloy(low alloyed)is beneficial for long-term sustainable development of metal materials.Creating a nanocrystalline microstructure is a desirable approach to improve biodegradability and mechanical properties of lean biomedical Mg alloy,but it is nearly impossible to realize.In the present study,the bulk nanocrystalline Mg alloy(average grain size:~70 nm)was successfully obtained by hot rolling process of a lean Mg-2wt.%Zn(Z2)alloy and both high strength((223 MPa(YS)and 260 MPa(UTS))and good corrosion resistance(corrosion rate in vivo:0.2 mm/year)could be achieved.The microstructure evolution during the rolling process was analyzed and discussed.Several factors including large strain,fine grains,strong basal texture,high temperature and Zn segregation conjointly provided the possibility for the activation of pyramidal<c+a>slip to produce nanocrystals.This finding could provide a new development direction and field of application for lean biomedical Mg alloys.展开更多
Magnesium(Mg)is a promising biomedical metal because of its biodegradability.The crevice between tissue and Mg implant can not be neglected in some implantation sites due to inducing crevice corrosion of Mg.In this pa...Magnesium(Mg)is a promising biomedical metal because of its biodegradability.The crevice between tissue and Mg implant can not be neglected in some implantation sites due to inducing crevice corrosion of Mg.In this paper,a new single mold was designed to build the in vitro experimental setup and four kinds of solutions,i.e.the deionized water(DW),the 0.9 wt.%sodium chloride solution(NaCl),the phosphate buffer saline(PBS)and the modified simulated body fluid(m-SBF)were used to explore necessary factors of crevice corrosion in Mg.It was observed that crevice corrosion in Mg sheets would occur in NaCl and PBS solution under 0.2,0.5 and 0.8 mm crevice thickness.And it was found that there were two necessary factors,i.e.chloride ion and crevice dimension,in crevice corrosion.For the high-purity Mg cannulated screws,crevice corrosion could occur inside tunnel when immersed in PBS.展开更多
基金funded by the National Key Research and Development Program of China(No.2018YFC1106600,No.2016YFC1102400)the Natural Science Foundation of China(NSFC No.51571142).
文摘Magnesium(Mg)and its alloys as temporary medical implants with biodegradable and properly mechanical properties have been investigated for a long time.There are already three kinds of biodegradable Mg implants which are approved by Conformite Europeene(CE)or Korea Food and Drug Administration(KFDA),but not China Food and Drug Administration(CFDA,now it is National Medical Products Administration,NMPA).As we know,Chinese researchers,surgeons,and entrepreneurs have tried a lot to research and develop biodegradable Mg implants which might become other new approved implants for clinical applications.So in this review,we present the representative Mg implants of three categories,orthopedic implants,surgical implants,and intervention implants and provide an overview of current achievement in China from academic publications and Chinese patents.We would like to provide a systematic way to translate Mg and its alloy implants from experiment designs to clinical products.
基金financially supported by the National Natural Science Foundation of China (Nos.51401126 and 51571142)
文摘Tantalum exhibits excellent biocompatibility and good chemical stability, which has been employed in dental and orthopedic applications.The local microenvironment of the surface of implants influence determines the surrounding cell responses.In this work, nano-dimpled structure on the surface of pure tantalum was fabricated by electrochemical anodization.The surface morphology of the nano-dimpled structure was observed, and the dimensions of the nano-dimpled structure were measured by scanning electron microscopy(SEM).The surface roughness of the sample with nano-dimpled structure was measured by atomic force microscopy(AFM).The results show that the diameter of nano-dimpled ranges from 40 to 180 nm, and the higher the applied voltage, the larger the diameter.Moreover, nano-dimpled structure has good hydrophilicity.In vitro results show that nano-dimpled structure can promote the adhesion and proliferation of mouse cranial anterior bone(MC-3T3-E1) cells.The filopodia of MC-3T3-E1 cells can be fully extended on this nano-dimpled structure.On the surface of the nano-dimpled structure with a dimple size of 40 nm, the cells have the longest aspect ratio.The small dimple size of the nanodimpled structure is beneficial to cell proliferation and osteogenic differentiation.
基金the National Key Research and Development Program of China(2018YFC1106600)the Interdisciplinary Program of Shanghai Jiao Tong University(ZH2018QNB07)。
文摘Relapse and metastasis of tumor may occur for osteosarcoma(OS)patients after clinical resection.Conventional metallic scaffolds provide sufficient mechanical support to the defected bone but fail to eradicate recurring tumors.Here we report that biodegradable magnesium(Mg)wirebased implant can inhibit OS growth.In brief,the Mg wires release Mg ions to activate the transport of zinc finger protein Snail1 from cytoplasm to cell nucleus,which induces apoptosis and inhibits proliferation of OS cells through a parallel antitumor signaling pathway of miRNA-181d-5p/TIMP3 and miRNA-181c-5p/NLK downstream.Simultaneously,the hydrogen gas evolution from Mg wires eliminates intracellular excessive reactive oxygen species,by which the growth of bone tumor cells is suppressed.The subcutaneous tumor-bearing experiment of OS cells in nude mice further confirms that Mg wires can effectively inhibit the growth of tumors and prolong the survival of tumor-bearing mice.In addition,Mg wires have no toxicity to normal cells and tissues.These results suggest that Mg implant is a potential anti-tumor scaffold for OS patients.
基金The authors are grateful for support from the National Key Research and Development Program of China(No.2018YFC1106600)the Interdisciplinary Program of Shanghai Jiao Tong University(No.ZH2018QNB07).Thanks to Xinyue Liu(Massachusetts Institute of Technology,MIT)for suggestions for this paper.
文摘Hydrogen has been used to suppress tumor growth with considerable efficacy.Inhalation of hydrogen gas and oral ingestion of hydrogen-rich saline are two common systemic routes of hydrogen administration.We have developed a topical delivery method of hydrogen at targeted sites through the degradation of magnesium-based biomaterials.However,the underlying mechanism of hydrogen’s role in cancer treatment remains ambiguous.Here,we investigate the mechanism of tumor cell apoptosis triggered by the hydrogen released from magnesium-based biomaterials.We find that the localized release of hydrogen increases the expression level of P53 tumor suppressor proteins,as demonstrated by the in vitro RNA sequencing and protein expression analysis.Then,the P53 proteins disrupt the membrane potential of mitochondria,activate autophagy,suppress the reactive oxygen species in cancer cells,and finally result in tumor suppression.The anti-tumor efficacy of magnesium-based biomaterials is further validated in vivo by inserting magnesium wire into the subcutaneous tumor in a mouse.We also discovered that the minimal hydrogen concentration from magnesium wires to trigger substantial tumor apoptosis is 91.2μL/mm^(3)per day,which is much lower than that required for hydrogen inhalation.Taken together,these findings reveal the release of H2 from magnesium-based biomaterial exerts its anti-tumoral activity by activating the P53-mediated lysosome-mitochondria apoptosis signaling pathway,which strengthens the therapeutic potential of this biomaterial as localized anti-tumor treatment.
基金This work was funded by the National Key R&D Program of China(No.2018YFC1106600)the“Science and Technology Innovation 2025”Major Special Project of Ningbo(No.2019B10064).
文摘Lean alloy(low alloyed)is beneficial for long-term sustainable development of metal materials.Creating a nanocrystalline microstructure is a desirable approach to improve biodegradability and mechanical properties of lean biomedical Mg alloy,but it is nearly impossible to realize.In the present study,the bulk nanocrystalline Mg alloy(average grain size:~70 nm)was successfully obtained by hot rolling process of a lean Mg-2wt.%Zn(Z2)alloy and both high strength((223 MPa(YS)and 260 MPa(UTS))and good corrosion resistance(corrosion rate in vivo:0.2 mm/year)could be achieved.The microstructure evolution during the rolling process was analyzed and discussed.Several factors including large strain,fine grains,strong basal texture,high temperature and Zn segregation conjointly provided the possibility for the activation of pyramidal<c+a>slip to produce nanocrystals.This finding could provide a new development direction and field of application for lean biomedical Mg alloys.
基金financially supported by the Natural Science Foundation of China(No.51571142)the National Key Research and Development Program of China(No.2018YFC1106600)。
文摘Magnesium(Mg)is a promising biomedical metal because of its biodegradability.The crevice between tissue and Mg implant can not be neglected in some implantation sites due to inducing crevice corrosion of Mg.In this paper,a new single mold was designed to build the in vitro experimental setup and four kinds of solutions,i.e.the deionized water(DW),the 0.9 wt.%sodium chloride solution(NaCl),the phosphate buffer saline(PBS)and the modified simulated body fluid(m-SBF)were used to explore necessary factors of crevice corrosion in Mg.It was observed that crevice corrosion in Mg sheets would occur in NaCl and PBS solution under 0.2,0.5 and 0.8 mm crevice thickness.And it was found that there were two necessary factors,i.e.chloride ion and crevice dimension,in crevice corrosion.For the high-purity Mg cannulated screws,crevice corrosion could occur inside tunnel when immersed in PBS.
