Biodegradable metals have been increasingly utilized clinically due to their biosafety and pro-osteogenic prop-erties.However,conventional monolayer cell-based preclinical safety evaluation methods based on ISO10993-5...Biodegradable metals have been increasingly utilized clinically due to their biosafety and pro-osteogenic prop-erties.However,conventional monolayer cell-based preclinical safety evaluation methods based on ISO10993-5 consistently indicate significant cytotoxicity that contradicts in vivo outcomes.In this study,we aimed to establish an in vitro evaluation model that better correlates with in vivo performance.Three-layer BMSC cell sheets were constructed using layer-by-layer assembly.Histological analyses revealed a stable three-dimensional structure with elevated cell-cell interaction proteins,including N-Cadherin,Fibronectin,and Vinculin,along with enhanced osteogenic potential.The cytotoxicity of 4N pure Mg was evaluated in both cell sheet and monolayer co-culture models.Flow cytometry showed higher Ki67 expression and lower ROS levels and apoptosis rate in cell sheets.ShRNA-mediated silencing of N-Cadherin in cell sheets significantly compromised their cytopro-tective capacity against Mg metal-induced toxicity.Osteogenesis-related gene expression correlation analysis between in vitro co-culture models and in vivo femur implantation models was conducted using RNA-seq and qRT-PCR.Results showed that 4N pure Mg enhanced osteogenic genes(BMP2R,RUNX2,and SP7)in cell sheets,consistent with in vivo patterns but contrary to monolayer models.Various Mg-based metals(4N/5N Pure Mg,ZE21B,and WE43)were evaluated in cell sheet defect,monolayer defect,and cranial defect models.5N Pure Mg,ZE21B,and WE43 promoted defect healing in both cranial defect and cell sheets,but showed no positive effect in monolayers.Collectively,cell sheet models correlated well with in vivo results,suggesting their potential as alternative in vitro evaluation models,thereby accelerating clinical translation of Mg-based biomaterials.展开更多
The high temperature tensile and fracture behavior of Zr50Al40Cu10 metallic glass at the temperature range in the vicinity of glass transition were investigated. Tensile tests were carried out at room temperature, 350...The high temperature tensile and fracture behavior of Zr50Al40Cu10 metallic glass at the temperature range in the vicinity of glass transition were investigated. Tensile tests were carried out at room temperature, 350-420 ℃, and in the supercooled liquid region temperature range, respectively. Obvious plastic deformation was initiated at temperature about 80 °C lower than the glass transition temperature. The ultimate tensile strength decreases with the increase of testing temperature and the ductility increases with temperature. At temperature higher than Tg, viscous flow of Non-Newtonian fluid led to super plastic deformation behavior. The deformation process under tension was inhomogeneous, and remarkable serrations were observed on the stress-strain curve near glass transition temperature.展开更多
基金financially funded by National Key Research and Development Program of China(2021YFC2400703)the National Nat-ural Science Foundation of China(NSFC)(52171234)+1 种基金Beijing Municipal Science and Technology Project(Z211100002921066)Peking Univer-sity National Clinical Key Specialty Translation Support Project(PKUSSNKP-Т202104).
文摘Biodegradable metals have been increasingly utilized clinically due to their biosafety and pro-osteogenic prop-erties.However,conventional monolayer cell-based preclinical safety evaluation methods based on ISO10993-5 consistently indicate significant cytotoxicity that contradicts in vivo outcomes.In this study,we aimed to establish an in vitro evaluation model that better correlates with in vivo performance.Three-layer BMSC cell sheets were constructed using layer-by-layer assembly.Histological analyses revealed a stable three-dimensional structure with elevated cell-cell interaction proteins,including N-Cadherin,Fibronectin,and Vinculin,along with enhanced osteogenic potential.The cytotoxicity of 4N pure Mg was evaluated in both cell sheet and monolayer co-culture models.Flow cytometry showed higher Ki67 expression and lower ROS levels and apoptosis rate in cell sheets.ShRNA-mediated silencing of N-Cadherin in cell sheets significantly compromised their cytopro-tective capacity against Mg metal-induced toxicity.Osteogenesis-related gene expression correlation analysis between in vitro co-culture models and in vivo femur implantation models was conducted using RNA-seq and qRT-PCR.Results showed that 4N pure Mg enhanced osteogenic genes(BMP2R,RUNX2,and SP7)in cell sheets,consistent with in vivo patterns but contrary to monolayer models.Various Mg-based metals(4N/5N Pure Mg,ZE21B,and WE43)were evaluated in cell sheet defect,monolayer defect,and cranial defect models.5N Pure Mg,ZE21B,and WE43 promoted defect healing in both cranial defect and cell sheets,but showed no positive effect in monolayers.Collectively,cell sheet models correlated well with in vivo results,suggesting their potential as alternative in vitro evaluation models,thereby accelerating clinical translation of Mg-based biomaterials.
基金financially supported by the National Natural Sciences Foundation of China(Grant No.51171119 and No.51401129)
文摘The high temperature tensile and fracture behavior of Zr50Al40Cu10 metallic glass at the temperature range in the vicinity of glass transition were investigated. Tensile tests were carried out at room temperature, 350-420 ℃, and in the supercooled liquid region temperature range, respectively. Obvious plastic deformation was initiated at temperature about 80 °C lower than the glass transition temperature. The ultimate tensile strength decreases with the increase of testing temperature and the ductility increases with temperature. At temperature higher than Tg, viscous flow of Non-Newtonian fluid led to super plastic deformation behavior. The deformation process under tension was inhomogeneous, and remarkable serrations were observed on the stress-strain curve near glass transition temperature.
