Melt extrusion-based additive manufacturing(ME-AM)is a promising technique to fabricate porous scaffolds for tissue engi-neering applications.However,most synthetic semicrystalline polymers do not possess the intrinsi...Melt extrusion-based additive manufacturing(ME-AM)is a promising technique to fabricate porous scaffolds for tissue engi-neering applications.However,most synthetic semicrystalline polymers do not possess the intrinsic biological activity required to control cell fate.Grafting of biomolecules on polymeric surfaces of AM scaffolds enhances the bioactivity of a construct;however,there are limited strategies available to control the surface density.Here,we report a strategy to tune the surface density of bioactive groups by blending a low molecular weight poly(ε-caprolactone)5k(PCL5k)containing orthogonally reactive azide groups with an unfunctionalized high molecular weight PCL75k at different ratios.Stable porous three-dimensional(3D)scaf-folds were then fabricated using a high weight percentage(75 wt.%)of the low molecular weight PCL 5k.As a proof-of-concept test,we prepared films of three different mass ratios of low and high molecular weight polymers with a thermopress and reacted with an alkynated fluorescent model compound on the surface,yielding a density of 201-561 pmol/cm^(2).Subsequently,a bone morphogenetic protein 2(BMP-2)-derived peptide was grafted onto the films comprising different blend compositions,and the effect of peptide surface density on the osteogenic differentiation of human mesenchymal stromal cells(hMSCs)was assessed.After two weeks of culturing in a basic medium,cells expressed higher levels of BMP receptor II(BMPRII)on films with the conjugated peptide.In addition,we found that alkaline phosphatase activity was only significantly enhanced on films contain-ing the highest peptide density(i.e.,561 pmol/cm^(2)),indicating the importance of the surface density.Taken together,these results emphasize that the density of surface peptides on cell differentiation must be considered at the cell-material interface.Moreover,we have presented a viable strategy for ME-AM community that desires to tune the bulk and surface functionality via blending of(modified)polymers.Furthermore,the use of alkyne-azide“click”chemistry enables spatial control over bioconjugation of many tissue-specific moieties,making this approach a versatile strategy for tissue engineering applications.展开更多
In 2023,the majority of the Earth witnessed its warmest boreal summer and autumn since 1850.Whether 2023 will indeed turn out to be the warmest year on record and what caused the astonishingly large margin of warming ...In 2023,the majority of the Earth witnessed its warmest boreal summer and autumn since 1850.Whether 2023 will indeed turn out to be the warmest year on record and what caused the astonishingly large margin of warming has become one of the hottest topics in the scientific community and is closely connected to the future development of human society.We analyzed the monthly varying global mean surface temperature(GMST)in 2023 and found that the globe,the land,and the oceans in 2023 all exhibit extraordinary warming,which is distinct from any previous year in recorded history.Based on the GMST statistical ensemble prediction model developed at the Institute of Atmospheric Physics,the GMST in 2023 is predicted to be 1.41℃±0.07℃,which will certainly surpass that in 2016 as the warmest year since 1850,and is approaching the 1.5℃ global warming threshold.Compared to 2022,the GMST in 2023 will increase by 0.24℃,with 88%of the increment contributed by the annual variability as mostly affected by El Niño.Moreover,the multidecadal variability related to the Atlantic Multidecadal Oscillation(AMO)in 2023 also provided an important warming background for sparking the GMST rise.As a result,the GMST in 2023 is projected to be 1.15℃±0.07℃,with only a 0.02℃ increment,if the effects of natural variability—including El Niño and the AMO—are eliminated and only the global warming trend is considered.展开更多
To investigate the interaction of the bolt-reinforced rock and the surface support,an analytical model of the convergence-confinement type is proposed,considering the sequential installation of the fully grouted rockb...To investigate the interaction of the bolt-reinforced rock and the surface support,an analytical model of the convergence-confinement type is proposed,considering the sequential installation of the fully grouted rockbolts and the surface support.The rock mass is assumed to be elastic-brittle-plastic material,obeying the linear Mohr-Coulomb criterion or the non-linear Hoek-Brown criterion.According to the strain states of the tunnel wall at bolt and surface support installation and the relative magnitude between the bolt length and the plastic depth during the whole process,six cases are categorized upon solving the problem.Each case is divided into three stages due to the different effects of the active rockbolts and the passive surface support.The fictitious pressure is introduced to quantify the threedimensional(3D)effect of the tunnel face,and thus,the actual physical location along the tunnel axis of the analytical section can be considered.By using the bolt-rock strain compatibility and the rocksurface support displacement compatibility conditions,the solutions of longitudinal tunnel displacement and the reaction pressure of surface support along the tunnel axis are obtained.The proposed analytical solutions are validated by a series of 3D numerical simulations.Extensive parametric studies are conducted to examine the effect of the typical parameters of rockbolts and surface support on the tunnel displacement and the reaction pressure of the surface support under different rock conditions.The results show that the rockbolts are more effective in controlling the tunnel displacement than the surface support,which should be installed as soon as possible with a suitable length.For tunnels excavated in weak rocks or with restricted displacement control requirements,the surface support should also be installed or closed timely with a certain stiffness.The proposed method provides a convenient alternative approach for the optimization of rockbolts and surface support at the preliminary stage of tunnel design.展开更多
基金the European Research Council starting grant “Cell Hybridge” for financial support under the Horizon2020 framework program (Grant#637308)the Province of Limburg for support and funding
文摘Melt extrusion-based additive manufacturing(ME-AM)is a promising technique to fabricate porous scaffolds for tissue engi-neering applications.However,most synthetic semicrystalline polymers do not possess the intrinsic biological activity required to control cell fate.Grafting of biomolecules on polymeric surfaces of AM scaffolds enhances the bioactivity of a construct;however,there are limited strategies available to control the surface density.Here,we report a strategy to tune the surface density of bioactive groups by blending a low molecular weight poly(ε-caprolactone)5k(PCL5k)containing orthogonally reactive azide groups with an unfunctionalized high molecular weight PCL75k at different ratios.Stable porous three-dimensional(3D)scaf-folds were then fabricated using a high weight percentage(75 wt.%)of the low molecular weight PCL 5k.As a proof-of-concept test,we prepared films of three different mass ratios of low and high molecular weight polymers with a thermopress and reacted with an alkynated fluorescent model compound on the surface,yielding a density of 201-561 pmol/cm^(2).Subsequently,a bone morphogenetic protein 2(BMP-2)-derived peptide was grafted onto the films comprising different blend compositions,and the effect of peptide surface density on the osteogenic differentiation of human mesenchymal stromal cells(hMSCs)was assessed.After two weeks of culturing in a basic medium,cells expressed higher levels of BMP receptor II(BMPRII)on films with the conjugated peptide.In addition,we found that alkaline phosphatase activity was only significantly enhanced on films contain-ing the highest peptide density(i.e.,561 pmol/cm^(2)),indicating the importance of the surface density.Taken together,these results emphasize that the density of surface peptides on cell differentiation must be considered at the cell-material interface.Moreover,we have presented a viable strategy for ME-AM community that desires to tune the bulk and surface functionality via blending of(modified)polymers.Furthermore,the use of alkyne-azide“click”chemistry enables spatial control over bioconjugation of many tissue-specific moieties,making this approach a versatile strategy for tissue engineering applications.
基金supported by the Key Research Program of Frontier Sciences,Chinese Academy of Sciences(Grant No.ZDBS-LY-DQC010)the National Natural Science Foundation of China(Grant No.42175045).
文摘In 2023,the majority of the Earth witnessed its warmest boreal summer and autumn since 1850.Whether 2023 will indeed turn out to be the warmest year on record and what caused the astonishingly large margin of warming has become one of the hottest topics in the scientific community and is closely connected to the future development of human society.We analyzed the monthly varying global mean surface temperature(GMST)in 2023 and found that the globe,the land,and the oceans in 2023 all exhibit extraordinary warming,which is distinct from any previous year in recorded history.Based on the GMST statistical ensemble prediction model developed at the Institute of Atmospheric Physics,the GMST in 2023 is predicted to be 1.41℃±0.07℃,which will certainly surpass that in 2016 as the warmest year since 1850,and is approaching the 1.5℃ global warming threshold.Compared to 2022,the GMST in 2023 will increase by 0.24℃,with 88%of the increment contributed by the annual variability as mostly affected by El Niño.Moreover,the multidecadal variability related to the Atlantic Multidecadal Oscillation(AMO)in 2023 also provided an important warming background for sparking the GMST rise.As a result,the GMST in 2023 is projected to be 1.15℃±0.07℃,with only a 0.02℃ increment,if the effects of natural variability—including El Niño and the AMO—are eliminated and only the global warming trend is considered.
基金funding support from the Fundamental Research Funds for the Central Universities(Grant No.2023JBZY024)the National Natural Science Foundation of China(Grant Nos.52208382 and 52278387).
文摘To investigate the interaction of the bolt-reinforced rock and the surface support,an analytical model of the convergence-confinement type is proposed,considering the sequential installation of the fully grouted rockbolts and the surface support.The rock mass is assumed to be elastic-brittle-plastic material,obeying the linear Mohr-Coulomb criterion or the non-linear Hoek-Brown criterion.According to the strain states of the tunnel wall at bolt and surface support installation and the relative magnitude between the bolt length and the plastic depth during the whole process,six cases are categorized upon solving the problem.Each case is divided into three stages due to the different effects of the active rockbolts and the passive surface support.The fictitious pressure is introduced to quantify the threedimensional(3D)effect of the tunnel face,and thus,the actual physical location along the tunnel axis of the analytical section can be considered.By using the bolt-rock strain compatibility and the rocksurface support displacement compatibility conditions,the solutions of longitudinal tunnel displacement and the reaction pressure of surface support along the tunnel axis are obtained.The proposed analytical solutions are validated by a series of 3D numerical simulations.Extensive parametric studies are conducted to examine the effect of the typical parameters of rockbolts and surface support on the tunnel displacement and the reaction pressure of the surface support under different rock conditions.The results show that the rockbolts are more effective in controlling the tunnel displacement than the surface support,which should be installed as soon as possible with a suitable length.For tunnels excavated in weak rocks or with restricted displacement control requirements,the surface support should also be installed or closed timely with a certain stiffness.The proposed method provides a convenient alternative approach for the optimization of rockbolts and surface support at the preliminary stage of tunnel design.
