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
For large segmental bone defects,porous titanium scaffolds have some advantages,however,they lack electrical activity which hinders their further use.In this study,a barium titanate(BaTiO3)piezoelectric ceramic was us...For large segmental bone defects,porous titanium scaffolds have some advantages,however,they lack electrical activity which hinders their further use.In this study,a barium titanate(BaTiO3)piezoelectric ceramic was used to modify the surface of a porous Ti6Al4V scaffold(pTi),which was characterized by scanning electron microscopy,energy dispersive spectroscopy,X-ray photoelectron spectroscopy,and roughness and water contact angle analyses.Low intensity pulsed ultrasound(LIPUS)was applied in vitro and in vivo study.The activity of bone marrow mesenchymal stem cells,including adhesion,proliferation,and gene expression,was significantly superior in the BaTiO3/pTi,pTi+LIPUS,and BaTiO3/pTi+LIPUS groups than in the pTi group.The activity was also higher in the BaTiO3/pTi+LIPUS group than in the BaTiO3/pTi and pTi+LIPUS groups.Additionally,micro-computed tomography,the mineral apposition rate,histomorphology,and the peak pull-out load showed that these scaffold conditions significantly enhanced osteogenesis and osseointegration 6 and 12 weeks after implantation in large segmental bone defects in the radius of rabbits compared with those resulting from the pTi condition.Consequently,the improved osteogenesis and osseointegration make the BaTiO3/pTi+LIPUS a promising method to promote bone regeneration in large segmental bone defects for clinical application.展开更多
Mussel-derived nacre and pearl,which are natural composites composed CaCO3 platelets and interplatelet organic matrix,have recently gained interest due to their osteogenic potential.The crystal form of CaCO3 could be ...Mussel-derived nacre and pearl,which are natural composites composed CaCO3 platelets and interplatelet organic matrix,have recently gained interest due to their osteogenic potential.The crystal form of CaCO3 could be either aragonite or vaterite depending on the characteristics of mineralization template within pearls.So far,little attention has been paid on the different osteogenic capacities between aragonite and vaterite pearl.In the current work,aragonite or vaterite pearl powders were incorporated into poly-L-lactic acid(PLLA)scaffold as bio-functional fillers for enhanced osteogenesis.In intro results revealed that PLLA/aragonite scaffold possessed stronger stimulatory effect on SaOS-2 cell proliferation and differentiation,evidenced by the enhanced cell viability,alkaline phosphatase activity,collagen synthesis and gene expressions of osteogenic markers including osteocalcin,osteopotin and bone sialoprotein.The bone regeneration potential of various scaffolds was evaluated in vivo employing a rabbit critical-sized radial bone defect model.The X-ray and micro-CT results showed that significant bone regeneration and bridging were achieved in defects implanted with composite scaffolds,while less bone formation and non-bridging were found for pure PLLA group.Histological evaluation using Masson's trichrome and hematoxylin/eosin(H&E)staining indicated a typical endochondral bone formation process conducted at defect sites treated with composite scaffolds.Through three-point bending test,the limbs implanted with PLLA/aragonite scaffold were found to bear significantly higher bending load compared to other two groups.Together,it is suggested that aragonite pearl has superior osteogenic capacity over vaterite pearl and PLLA/aragonite scaffold can be employed as a potential bone graft for bone regeneration.展开更多
So far,how to achieve the optimal regenerative repair of large load-bearing bone defects using artificial bone grafts is a huge challenge in clinic.In this study,a strategy of combining osteoinductive biphasic calcium...So far,how to achieve the optimal regenerative repair of large load-bearing bone defects using artificial bone grafts is a huge challenge in clinic.In this study,a strategy of combining osteoinductive biphasic calcium phosphate(BCP)bioceramic scaffolds with intramedullary nail fixation for creating stable osteogenic microenvironment was applied to repair large segmental bone defects(3.0 cm in length)in goat femur model.The material characterization results showed that the BCP scaffold had the initial compressive strength of over 2.0 MPa,and total porosity of 84%.The cell culture experiments demonstrated that the scaffold had the excellent ability to promote the proliferation and osteogenic differentiation of rat bone marrow-derived mesenchymal stem cells(BMSCs).The in vivo results showed that the intramedullary nail fixation maintained the initial stability and structural integrity of the implants at early stage,promoting the osteogenic process both guided and induced by the BCP scaffolds.At 9 months postoperatively,good integration between the implants and host bone was observed,and a large amount of newborn bones formed,accompanying with the degradation of the material.At 18 months postoperatively,almost the complete new bone substitution in the defect area was achieved.The maximum bending strength of the repaired bone defects reached to the 100% of normal femur at 18 months post-surgery.Our results demonstrated the good potential of osteoinductive BCP bioceramics in the regenerative repair of large load-bearing bone defects.The current study could provide an effective method to treat the clinical large segmental bone defects.展开更多
The custom-tailored medicine requires a developmental strategy that integrates excellent osteogene-sis with mechanical stability to enhance the reconstruction of the critical-size bone defect(CSBD)and the healing proc...The custom-tailored medicine requires a developmental strategy that integrates excellent osteogene-sis with mechanical stability to enhance the reconstruction of the critical-size bone defect(CSBD)and the healing process in weight-bearing bone.We prepared three-dimensional(3D)printed biphasic cal-cium phosphate(BCP)scaffolds composited with nano-graphene oxide(GO).The biological effects of the GO/BCP composite scaffolds could induce the differentiation of rat bone marrow stem cells(BM-SCs)and the migration of human umbilical vein endothelial cells(HUVECs)for bone repair.The proper ratio of GO in the composite scaffold regulated the composites’surface roughness and hydrophilicity to a suitable range for the adhesion and proliferation of BMSCs and HUVECs.Besides,the GO/BCP composite scaffold increased osteogenesis and angiogenesis by activating BMP-2,RUNX-2,Smad1/4,and VEGF.The customized intramedullary nail combined with GO/BCP scaffold was applied to repair CSBD(2.0 cm in length)in a beagle femur model.This fixation strategy was confirmed by finite element analysis.In vivo,the results indicated that the custom-made internal fixation provided sufficient stability in the early stage,ensuring bone healing in a considerable mechanical environment.At 9 months postoperatively,longitudi-nal bony union and blood vessels in osteon were observed in the CSBD area with partial degradation in the 0.3%GO/BCP group.In the three-point bending test,the ultimate load of 0.3%GO/BCP group reached over 50%of the normal femur at 9 months after repair.These results showed a promising application of osteogenic GO/BCP scaffold and custom-made intramedullary nails in repairing CSBD of the beagle femur.This effective strategy could provide an option to treat the clinical CSBD in weight-bearing bones.展开更多
Background Given that three-dimensional finite element models have been successfully used to analyze biomechanics in orthopedics-related research, this study aimed to establish a finite element model of the pelvic bon...Background Given that three-dimensional finite element models have been successfully used to analyze biomechanics in orthopedics-related research, this study aimed to establish a finite element model of the pelvic bone and three-fin acetabular component and evaluate biomechanical changes in this model after implantation of a three-fin acetabular prosthesis in a superior segmental bone defect of the acetabulum.展开更多
Recent developments in synthetic bone grafting materials and adjuvant therapeutic agents have opened the door to the regenerative reconstruction of critical-size long bone segmental defects resulting from trauma,osteo...Recent developments in synthetic bone grafting materials and adjuvant therapeutic agents have opened the door to the regenerative reconstruction of critical-size long bone segmental defects resulting from trauma,osteoporotic fractures or tumour resections.Polymeric scaffolds with controlled macroporosities,degradability,useful surgical handling characteristics,and the ability to deliver biotherapeutics to promote new bone ingrowth have been developed for this challenging orthopaedic application.This review highlights major classes of degradable synthetic polymers and their biomineral composites,including conventional and amphiphilic polyesters,polyanhydrides,polycarbonates,and polyethylene glycol-based hydrogels,that have been explored for the regenerative reconstruction of critical-size long bone segmental defects over the past two decades.The pros and cons of these synthetic scaffold materials are presented in the context of enabling or impeding the functional(mechanical and radiographic)repair of a long bone segmental defect,with the long bone regeneration outcomes compared with healthy long bone controls or results achieved with current grafting standards.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supported by grants from the National Key Research and Development Program of China(grant number 2017YFC1104901)to Zheng Guothe National Natural Science Foundation of China(grant number 51771227)to Zheng Guo+2 种基金the Youth Development Program of Chinese People's Liberation Army(No.20QNPY069)to Bo Fanthe National Natural Science Foundation of China(No.31800812)to Bo Fanthe National Natural Science Foundation of China(grant number 51771227)to Zheng Guo.
文摘For large segmental bone defects,porous titanium scaffolds have some advantages,however,they lack electrical activity which hinders their further use.In this study,a barium titanate(BaTiO3)piezoelectric ceramic was used to modify the surface of a porous Ti6Al4V scaffold(pTi),which was characterized by scanning electron microscopy,energy dispersive spectroscopy,X-ray photoelectron spectroscopy,and roughness and water contact angle analyses.Low intensity pulsed ultrasound(LIPUS)was applied in vitro and in vivo study.The activity of bone marrow mesenchymal stem cells,including adhesion,proliferation,and gene expression,was significantly superior in the BaTiO3/pTi,pTi+LIPUS,and BaTiO3/pTi+LIPUS groups than in the pTi group.The activity was also higher in the BaTiO3/pTi+LIPUS group than in the BaTiO3/pTi and pTi+LIPUS groups.Additionally,micro-computed tomography,the mineral apposition rate,histomorphology,and the peak pull-out load showed that these scaffold conditions significantly enhanced osteogenesis and osseointegration 6 and 12 weeks after implantation in large segmental bone defects in the radius of rabbits compared with those resulting from the pTi condition.Consequently,the improved osteogenesis and osseointegration make the BaTiO3/pTi+LIPUS a promising method to promote bone regeneration in large segmental bone defects for clinical application.
基金the financial support from the China Postdoctoral Science Foundation(2018M630909 and 2019T120711).
文摘Mussel-derived nacre and pearl,which are natural composites composed CaCO3 platelets and interplatelet organic matrix,have recently gained interest due to their osteogenic potential.The crystal form of CaCO3 could be either aragonite or vaterite depending on the characteristics of mineralization template within pearls.So far,little attention has been paid on the different osteogenic capacities between aragonite and vaterite pearl.In the current work,aragonite or vaterite pearl powders were incorporated into poly-L-lactic acid(PLLA)scaffold as bio-functional fillers for enhanced osteogenesis.In intro results revealed that PLLA/aragonite scaffold possessed stronger stimulatory effect on SaOS-2 cell proliferation and differentiation,evidenced by the enhanced cell viability,alkaline phosphatase activity,collagen synthesis and gene expressions of osteogenic markers including osteocalcin,osteopotin and bone sialoprotein.The bone regeneration potential of various scaffolds was evaluated in vivo employing a rabbit critical-sized radial bone defect model.The X-ray and micro-CT results showed that significant bone regeneration and bridging were achieved in defects implanted with composite scaffolds,while less bone formation and non-bridging were found for pure PLLA group.Histological evaluation using Masson's trichrome and hematoxylin/eosin(H&E)staining indicated a typical endochondral bone formation process conducted at defect sites treated with composite scaffolds.Through three-point bending test,the limbs implanted with PLLA/aragonite scaffold were found to bear significantly higher bending load compared to other two groups.Together,it is suggested that aragonite pearl has superior osteogenic capacity over vaterite pearl and PLLA/aragonite scaffold can be employed as a potential bone graft for bone regeneration.
基金supported by the National Key R&D Program of China(2016YFC1102000)Research on repair technology and equipment of war injury(AWS17J004-02)the Science and Technology Innovation Seedling Project of Sichuan Province,China(2021057).
文摘So far,how to achieve the optimal regenerative repair of large load-bearing bone defects using artificial bone grafts is a huge challenge in clinic.In this study,a strategy of combining osteoinductive biphasic calcium phosphate(BCP)bioceramic scaffolds with intramedullary nail fixation for creating stable osteogenic microenvironment was applied to repair large segmental bone defects(3.0 cm in length)in goat femur model.The material characterization results showed that the BCP scaffold had the initial compressive strength of over 2.0 MPa,and total porosity of 84%.The cell culture experiments demonstrated that the scaffold had the excellent ability to promote the proliferation and osteogenic differentiation of rat bone marrow-derived mesenchymal stem cells(BMSCs).The in vivo results showed that the intramedullary nail fixation maintained the initial stability and structural integrity of the implants at early stage,promoting the osteogenic process both guided and induced by the BCP scaffolds.At 9 months postoperatively,good integration between the implants and host bone was observed,and a large amount of newborn bones formed,accompanying with the degradation of the material.At 18 months postoperatively,almost the complete new bone substitution in the defect area was achieved.The maximum bending strength of the repaired bone defects reached to the 100% of normal femur at 18 months post-surgery.Our results demonstrated the good potential of osteoinductive BCP bioceramics in the regenerative repair of large load-bearing bone defects.The current study could provide an effective method to treat the clinical large segmental bone defects.
基金This work was financially supported,in part,by the Sci-ence and Technology Research Program of Sichuan Province(No.2020YFS0036,Dr.Tu)the 1·3·5 project for disciplines of excel-lence,West China Hospital,Sichuan University(No.ZYJC18036,Dr.Tu).
文摘The custom-tailored medicine requires a developmental strategy that integrates excellent osteogene-sis with mechanical stability to enhance the reconstruction of the critical-size bone defect(CSBD)and the healing process in weight-bearing bone.We prepared three-dimensional(3D)printed biphasic cal-cium phosphate(BCP)scaffolds composited with nano-graphene oxide(GO).The biological effects of the GO/BCP composite scaffolds could induce the differentiation of rat bone marrow stem cells(BM-SCs)and the migration of human umbilical vein endothelial cells(HUVECs)for bone repair.The proper ratio of GO in the composite scaffold regulated the composites’surface roughness and hydrophilicity to a suitable range for the adhesion and proliferation of BMSCs and HUVECs.Besides,the GO/BCP composite scaffold increased osteogenesis and angiogenesis by activating BMP-2,RUNX-2,Smad1/4,and VEGF.The customized intramedullary nail combined with GO/BCP scaffold was applied to repair CSBD(2.0 cm in length)in a beagle femur model.This fixation strategy was confirmed by finite element analysis.In vivo,the results indicated that the custom-made internal fixation provided sufficient stability in the early stage,ensuring bone healing in a considerable mechanical environment.At 9 months postoperatively,longitudi-nal bony union and blood vessels in osteon were observed in the CSBD area with partial degradation in the 0.3%GO/BCP group.In the three-point bending test,the ultimate load of 0.3%GO/BCP group reached over 50%of the normal femur at 9 months after repair.These results showed a promising application of osteogenic GO/BCP scaffold and custom-made intramedullary nails in repairing CSBD of the beagle femur.This effective strategy could provide an option to treat the clinical CSBD in weight-bearing bones.
文摘Background Given that three-dimensional finite element models have been successfully used to analyze biomechanics in orthopedics-related research, this study aimed to establish a finite element model of the pelvic bone and three-fin acetabular component and evaluate biomechanical changes in this model after implantation of a three-fin acetabular prosthesis in a superior segmental bone defect of the acetabulum.
基金This work is supported by an Alex Lemonade Stand Foundation Innovation Grant and a BRIDGE Award from the University of Massachusetts Medical School.
文摘Recent developments in synthetic bone grafting materials and adjuvant therapeutic agents have opened the door to the regenerative reconstruction of critical-size long bone segmental defects resulting from trauma,osteoporotic fractures or tumour resections.Polymeric scaffolds with controlled macroporosities,degradability,useful surgical handling characteristics,and the ability to deliver biotherapeutics to promote new bone ingrowth have been developed for this challenging orthopaedic application.This review highlights major classes of degradable synthetic polymers and their biomineral composites,including conventional and amphiphilic polyesters,polyanhydrides,polycarbonates,and polyethylene glycol-based hydrogels,that have been explored for the regenerative reconstruction of critical-size long bone segmental defects over the past two decades.The pros and cons of these synthetic scaffold materials are presented in the context of enabling or impeding the functional(mechanical and radiographic)repair of a long bone segmental defect,with the long bone regeneration outcomes compared with healthy long bone controls or results achieved with current grafting standards.