Mechanically strong magnesium-doped Ca-silicate bioceramic scaffolds have many advantages in repairing large segmental bone defects.Herein we combine β-TCP with 6 mol%magnesium-doped calcium silicate(Mg6)at three dif...Mechanically strong magnesium-doped Ca-silicate bioceramic scaffolds have many advantages in repairing large segmental bone defects.Herein we combine β-TCP with 6 mol%magnesium-doped calcium silicate(Mg6)at three different ratios(TCP,TCP+15%Mg6,TCP+85%Mg6)to find an appropriate ratio which can exert considerable influence on bone regeneration.In this study,the bioceramic scaffolds were assessed for mechanical strength,bioactive ion release,biocompatibility,and osteogenic capacity through in vitro testing.Additionally,the potential for promoting bone regeneration was investigated through in vivo implantation of porous tube-like scaffolds.The results showed that the compressive strength increased with the augmentation of Mg6 component.Especially the compressive strength of the TCP+85%Mg6 group reached 38.1±3.8 MPa,three times that of the other two groups.Furthermore,extensive in vivo investigations revealed that the TCP+85%Mg6 bioceramic scaffolds were particularly beneficial for the osteogenic capacity of critical-sized femoral defects(20 mm in length).Altogether,magnesium doping in bioceramic implants is a promising strategy to provide stronger mechanical support and enhance osteogenesis to accelerate the repair of large defects.展开更多
The pore architecture of porous scaffolds is a critical factor in osteogenesis,but it is a challenge to precisely configure strut-based scaffolds because of the inevitable filament corner and pore geometry deformation...The pore architecture of porous scaffolds is a critical factor in osteogenesis,but it is a challenge to precisely configure strut-based scaffolds because of the inevitable filament corner and pore geometry deformation.This study provides a pore architecture tailoring strategy in which a series of Mg-doped wollastonite scaffolds with fully interconnected pore networks and curved pore architectures called triply periodic minimal surfaces(TPMS),which are similar to cancellous bone,are fabricated by a digital light processing technique.The sheet-TPMS pore geometries(s-Diamond,s-Gyroid)contribute to a 3‒4-fold higher initial compressive strength and 20%-40%faster Mg-ion-release rate compared to the other-TPMS scaffolds,including Diamond,Gyroid,and the Schoen’s I-graph-Wrapped Package(IWP)in vitro.However,we found that Gyroid and Diamond pore scaffolds can significantly induce osteogenic differentiation of bone marrow mesenchymal stem cells(BMSCs).Analyses of rabbit experiments in vivo show that the regeneration of bone tissue in the sheet-TPMS pore geometry is delayed;on the other hand,Diamond and Gyroid pore scaffolds show notable neo-bone tissue in the center pore regions during the early stages(3-5 weeks)and the bone tissue uniformly fills the whole porous network after 7 weeks.Collectively,the design methods in this study provide an important perspective for optimizing the pore architecture design of bioceramic scaffolds to accelerate the rate of osteogenesis and promote the clinical translation of bioceramic scaffolds in the repair of bone defects.展开更多
Spatial dimension of pores and interconnection in macroporous scaffolds is of particular importance in facilitating endogenous cell migration and bone tissue ingrowth.However,it is still a challenge to widely tune str...Spatial dimension of pores and interconnection in macroporous scaffolds is of particular importance in facilitating endogenous cell migration and bone tissue ingrowth.However,it is still a challenge to widely tune structure parameters of scaffolds by conventional methods because of inevitable pore geometrical deformation and poor pore interconnectivity.Here,the long-term in vivo biological performances of nonstoichiometric bioceramic scaffolds with different pore dimensions were assessed in critical-size femoral bone defect model.The 6%Mg-substituted wollastonite(CSi-Mg6)powders were prepared via wet-chemical precipitation and the scaffolds elaborately printed by ceramic stereolithography,displaying designed constant pore strut and tailorable pore height(200,320,450,600μm),were investigated thoroughly in the bone regeneration process.Together with detailed structural stability and mechanical properties were collaboratively outlined.BothμCT and histological analyses indicated that bone tissue ingrowth was retarded in 200μm scaffolds in the whole stage(2-16 weeks)but the 320μm scaffolds showed appreciable bone tissue in the center of porous constructs at 6-10 weeks and matured bone tissue were uniformly invaded in the whole pore networks at 16 weeks.Interestingly,the neo-tissue ingrowth was facilitated in the 450μm and 600μm scaffolds after 2 weeks and higher extent of bone regeneration and remodeling at the later stage.These new findings provide critical information on how engineered porous architecture impact bone regeneration in vivo.Simultaneously,this study shows important implications for optimizing the porous scaffolds design by advanced additive manufacture technique to match the clinical translation with high performance.展开更多
Mechanical strength and its long-term stability of bioceramic scaffolds is still a problem to treat the osteonecrosis of the femoral head.Considering the long-term stability of diopside(DIO)ceramic but poor mechanical...Mechanical strength and its long-term stability of bioceramic scaffolds is still a problem to treat the osteonecrosis of the femoral head.Considering the long-term stability of diopside(DIO)ceramic but poor mechanical strength,we developed the DIO-based porous bioceramic composites via dilute magnesium substituted wollastonite reinforcing and three-dimensional(3D)printing.The experimental results showed that the secondary phase(i.e.10%magnesium substituting calcium silicate;CSM10)could readily improve the sintering property of the bioceramic composites(DIO/CSM10-x,x=0-30)with increasing the CSM10 content from 0%to 30%,and the presence of the CSM10 also improved the biomimetic apatite mineralization ability in the pore struts of the scaffolds.Furthermore,the flexible strength(12.5 -30 MPa)and compressive strength(14-37 MPa)of the 3D printed porous bioceramics remarkably increased with increasing CSM10 content,and the compressive strength of DIO/CSM10-30 showed a limited decay(from 37 MPa to 29 MPa)in the Tris buffer solution for a long time stage(8 weeks).These findings suggest that the new CSM10-reinforced diopside porous constructs possess excellent mechanical properties and can potentially be used to the clinic,especially for the treatment of osteonecrosis of the femoral head work as a bioceramic rod.展开更多
Pore architecture in bioceramic scaffolds plays an important role in facilitating vascularization efficiency during bone repair or orbital reconstruction.Many investigations have explored this relationship but lack in...Pore architecture in bioceramic scaffolds plays an important role in facilitating vascularization efficiency during bone repair or orbital reconstruction.Many investigations have explored this relationship but lack integrating pore architectural features in a scaffold,hindering optimization of architectural parameters(geometry,size and curvature)to improve vascularization and consequently clinical outcomes.To address this challenge,we have developed an integrating design strategy to fabricate different pore architectures(cube,gyroid and hexagon)with different pore dimensions(-350,500 and 650 lm)in the silicate-based bioceramic scaffolds via digital light processing technique.The sintered scaffolds maintained high-fidelity pore architectures similar to the printing model.The hexagon-and gyroid-pore scaffolds exhibited the highest and lowest compressive strength(from 15 to 55MPa),respectively,but the cube-pore scaffolds showed appreciable elastic modulus.Moreover,the gyroid-pore architecture contributed on a faster ion dissolution and mass decay in vitro.It is interesting that bothμCT and histological analyses indicate vascularization efficiency was challenged even in the 650-μm pore region of hexagon-pore scaffolds within 2weeks in rabbit models,but the gyroid-pore constructs indicated appreciable blood vessel networks even in the 350-μm pore region at 2weeks and high-density blood vessels were uniformly invaded in the 500-and 650-μm pore at 4weeks.Angiogenesis was facilitated in the cube-pore scaffolds in comparison with the hexagon-pore ones within 4weeks.These studies demonstrate that the continuous pore wall curvature feature in gyroid-pore architecture is an important implication for biodegradation,vascular cell migration and vessel ingrowth in porous bioceramic scaffolds.展开更多
基金support from the Medical Science and Technology Project of Zhejiang Province (2022+ZDXK-04)Zhejiang Provincial Basic Research for Public Welfare Funds (LGF20H060016,LGF21H060006,LGF22E030002)+1 种基金National Natural Science Foundation of China (82172419,82101649)Zheiang Provincial Natural Science Foundation of China (LZ22E020002).
文摘Mechanically strong magnesium-doped Ca-silicate bioceramic scaffolds have many advantages in repairing large segmental bone defects.Herein we combine β-TCP with 6 mol%magnesium-doped calcium silicate(Mg6)at three different ratios(TCP,TCP+15%Mg6,TCP+85%Mg6)to find an appropriate ratio which can exert considerable influence on bone regeneration.In this study,the bioceramic scaffolds were assessed for mechanical strength,bioactive ion release,biocompatibility,and osteogenic capacity through in vitro testing.Additionally,the potential for promoting bone regeneration was investigated through in vivo implantation of porous tube-like scaffolds.The results showed that the compressive strength increased with the augmentation of Mg6 component.Especially the compressive strength of the TCP+85%Mg6 group reached 38.1±3.8 MPa,three times that of the other two groups.Furthermore,extensive in vivo investigations revealed that the TCP+85%Mg6 bioceramic scaffolds were particularly beneficial for the osteogenic capacity of critical-sized femoral defects(20 mm in length).Altogether,magnesium doping in bioceramic implants is a promising strategy to provide stronger mechanical support and enhance osteogenesis to accelerate the repair of large defects.
基金The authors would like to acknowledge financial support from the National Key Research and Development Program of China(2017YFE0117700)National Natural Science Foundation of China(82172419,81902225,81871775)+1 种基金Natural Science Foundation of Zhejiang Province(LGF21H060006,LZ22E020002,LQ23H060005,LQ23H150004)Zhejiang Province Public Welfare Technology Application Research Project(LGF22E030002).
文摘The pore architecture of porous scaffolds is a critical factor in osteogenesis,but it is a challenge to precisely configure strut-based scaffolds because of the inevitable filament corner and pore geometry deformation.This study provides a pore architecture tailoring strategy in which a series of Mg-doped wollastonite scaffolds with fully interconnected pore networks and curved pore architectures called triply periodic minimal surfaces(TPMS),which are similar to cancellous bone,are fabricated by a digital light processing technique.The sheet-TPMS pore geometries(s-Diamond,s-Gyroid)contribute to a 3‒4-fold higher initial compressive strength and 20%-40%faster Mg-ion-release rate compared to the other-TPMS scaffolds,including Diamond,Gyroid,and the Schoen’s I-graph-Wrapped Package(IWP)in vitro.However,we found that Gyroid and Diamond pore scaffolds can significantly induce osteogenic differentiation of bone marrow mesenchymal stem cells(BMSCs).Analyses of rabbit experiments in vivo show that the regeneration of bone tissue in the sheet-TPMS pore geometry is delayed;on the other hand,Diamond and Gyroid pore scaffolds show notable neo-bone tissue in the center pore regions during the early stages(3-5 weeks)and the bone tissue uniformly fills the whole porous network after 7 weeks.Collectively,the design methods in this study provide an important perspective for optimizing the pore architecture design of bioceramic scaffolds to accelerate the rate of osteogenesis and promote the clinical translation of bioceramic scaffolds in the repair of bone defects.
基金support from the National Key Research and Development Program of China(2017YFE0117700,2018YC1105401)National Natural Science Foundation of China(81772311,81871775)the Science and Technology Department of Zhejiang Province Foundation(LGF18E020001,LGF20H060016).
文摘Spatial dimension of pores and interconnection in macroporous scaffolds is of particular importance in facilitating endogenous cell migration and bone tissue ingrowth.However,it is still a challenge to widely tune structure parameters of scaffolds by conventional methods because of inevitable pore geometrical deformation and poor pore interconnectivity.Here,the long-term in vivo biological performances of nonstoichiometric bioceramic scaffolds with different pore dimensions were assessed in critical-size femoral bone defect model.The 6%Mg-substituted wollastonite(CSi-Mg6)powders were prepared via wet-chemical precipitation and the scaffolds elaborately printed by ceramic stereolithography,displaying designed constant pore strut and tailorable pore height(200,320,450,600μm),were investigated thoroughly in the bone regeneration process.Together with detailed structural stability and mechanical properties were collaboratively outlined.BothμCT and histological analyses indicated that bone tissue ingrowth was retarded in 200μm scaffolds in the whole stage(2-16 weeks)but the 320μm scaffolds showed appreciable bone tissue in the center of porous constructs at 6-10 weeks and matured bone tissue were uniformly invaded in the whole pore networks at 16 weeks.Interestingly,the neo-tissue ingrowth was facilitated in the 450μm and 600μm scaffolds after 2 weeks and higher extent of bone regeneration and remodeling at the later stage.These new findings provide critical information on how engineered porous architecture impact bone regeneration in vivo.Simultaneously,this study shows important implications for optimizing the porous scaffolds design by advanced additive manufacture technique to match the clinical translation with high performance.
基金This work was supported by the Zhejiang Provincial Natural Science Foundation of China(LZ14E020001,LQ14H060003)gs2:National Science Foundation of China(51372218,81271956,81301326)the Science and Technology Department of Zhejiang Province Foundation(2015C33119,2014C33202).
文摘Mechanical strength and its long-term stability of bioceramic scaffolds is still a problem to treat the osteonecrosis of the femoral head.Considering the long-term stability of diopside(DIO)ceramic but poor mechanical strength,we developed the DIO-based porous bioceramic composites via dilute magnesium substituted wollastonite reinforcing and three-dimensional(3D)printing.The experimental results showed that the secondary phase(i.e.10%magnesium substituting calcium silicate;CSM10)could readily improve the sintering property of the bioceramic composites(DIO/CSM10-x,x=0-30)with increasing the CSM10 content from 0%to 30%,and the presence of the CSM10 also improved the biomimetic apatite mineralization ability in the pore struts of the scaffolds.Furthermore,the flexible strength(12.5 -30 MPa)and compressive strength(14-37 MPa)of the 3D printed porous bioceramics remarkably increased with increasing CSM10 content,and the compressive strength of DIO/CSM10-30 showed a limited decay(from 37 MPa to 29 MPa)in the Tris buffer solution for a long time stage(8 weeks).These findings suggest that the new CSM10-reinforced diopside porous constructs possess excellent mechanical properties and can potentially be used to the clinic,especially for the treatment of osteonecrosis of the femoral head work as a bioceramic rod.
基金financial support from the National Key Research and Development Program of China(2017YFE0117700)the National Natural Science Foundation of China(81871775,81902225,81772311)+1 种基金Zhejiang Provincial Natural Science Foundation of China(LBY21H060001,LGF21H060002,Z22E029971)the Medical and Health Research Project of Zhejiang Province(2020KY929,2020RC115).
文摘Pore architecture in bioceramic scaffolds plays an important role in facilitating vascularization efficiency during bone repair or orbital reconstruction.Many investigations have explored this relationship but lack integrating pore architectural features in a scaffold,hindering optimization of architectural parameters(geometry,size and curvature)to improve vascularization and consequently clinical outcomes.To address this challenge,we have developed an integrating design strategy to fabricate different pore architectures(cube,gyroid and hexagon)with different pore dimensions(-350,500 and 650 lm)in the silicate-based bioceramic scaffolds via digital light processing technique.The sintered scaffolds maintained high-fidelity pore architectures similar to the printing model.The hexagon-and gyroid-pore scaffolds exhibited the highest and lowest compressive strength(from 15 to 55MPa),respectively,but the cube-pore scaffolds showed appreciable elastic modulus.Moreover,the gyroid-pore architecture contributed on a faster ion dissolution and mass decay in vitro.It is interesting that bothμCT and histological analyses indicate vascularization efficiency was challenged even in the 650-μm pore region of hexagon-pore scaffolds within 2weeks in rabbit models,but the gyroid-pore constructs indicated appreciable blood vessel networks even in the 350-μm pore region at 2weeks and high-density blood vessels were uniformly invaded in the 500-and 650-μm pore at 4weeks.Angiogenesis was facilitated in the cube-pore scaffolds in comparison with the hexagon-pore ones within 4weeks.These studies demonstrate that the continuous pore wall curvature feature in gyroid-pore architecture is an important implication for biodegradation,vascular cell migration and vessel ingrowth in porous bioceramic scaffolds.