Additive manufacturing(AM)has revolutionized the design and manufacturing of patient-specific,three-dimensional(3D),complex porous structures known as scaffolds for tissue engineering applications.The use of advanced ...Additive manufacturing(AM)has revolutionized the design and manufacturing of patient-specific,three-dimensional(3D),complex porous structures known as scaffolds for tissue engineering applications.The use of advanced image acquisition techniques,image processing,and computer-aided design methods has enabled the precise design and additive manufacturing of anatomically correct and patient-specific implants and scaffolds.However,these sophisticated techniques can be timeconsuming,labor-intensive,and expensive.Moreover,the necessary imaging and manufacturing equipment may not be readily available when urgent treatment is needed for trauma patients.In this study,a novel design and AM methods are proposed for the development of modular and customizable scaffold blocks that can be adapted to fit the bone defect area of a patient.These modular scaffold blocks can be combined to quickly form any patient-specific scaffold directly from two-dimensional(2D)medical images when the surgeon lacks access to a 3D printer or cannot wait for lengthy 3D imaging,modeling,and 3D printing during surgery.The proposed method begins with developing a bone surface-modeling algorithm that reconstructs a model of the patient’s bone from 2D medical image measurements without the need for expensive 3D medical imaging or segmentation.This algorithm can generate both patient-specific and average bone models.Additionally,a biomimetic continuous path planning method is developed for the additive manufacturing of scaffolds,allowing porous scaffold blocks with the desired biomechanical properties to be manufactured directly from 2D data or images.The algorithms are implemented,and the designed scaffold blocks are 3D printed using an extrusion-based AM process.Guidelines and instructions are also provided to assist surgeons in assembling scaffold blocks for the self-repair of patient-specific large bone defects.展开更多
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
Complicated and large acetabular bone defects present the main challenges and difficulty in the revision of total hip arthroplasty(THA).This study aimed to explore the advantages of three-dimensional(3D)printing techn...Complicated and large acetabular bone defects present the main challenges and difficulty in the revision of total hip arthroplasty(THA).This study aimed to explore the advantages of three-dimensional(3D)printing technology in the reconstruction of such acetabular bone defects.We retrospectively analyzed the prognosis of four severe bone defects around the acetabulum in three patients who were treated using 3D printing technology.Reconstruction of bone defect by conventional methods was difficult in these patients.In this endeavor,we used radiographic methods,related computer software such as Materialise's interactive medical image control system and Siemens NX software,and actual surgical experience to estimate defect volume,prosthesis stability,and installation accuracy,respectively.Moreover,a Harris hip score was obtained to evaluate limb function.It was found that bone defects could be adequately reconstructed using a 3D printing prosthesis,and its stability was reliable.The Harris hip score indicated a very good functional recovery in all three patients.In conclusion,3D printing technology had a good therapeutic effect on both complex and large bone defects in the revision of THA.It was able to achieve good curative effects in patients with large bone 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
Bone is a complex biological tissue with a complicated hierarchical nanocomposite structure.The native microen-vironment of the bone tissue may be significantly disrupted by large physiological and pathological bone d...Bone is a complex biological tissue with a complicated hierarchical nanocomposite structure.The native microen-vironment of the bone tissue may be significantly disrupted by large physiological and pathological bone defects.Bone defects are often treated via complex surgical procedures that involve the application of autografts or al-lografts.While these grafting procedures often suffer from insufficient natural bone stock and immunorejection.Moreover,these traditional treatment methods fail to simulate a regenerative microenvironment,which plays a significant role in regeneration of bone tissue and repair of large bone defects.To this end,various biomimetic scaffolds have been devised to mimic the native microenvironment of bone and thereby to simultaneously re-pair bone defects and promote bone regeneration.We propose here a novel concept,in vivo bone regenerative microenvironment(BRM),which enables repair of large bone defects and enhances new bone tissue formation with external regulation.In this review,we mainly focus on materials and methods for fabrication of biomimetic scaffolds,as well as their therapeutic efficacy in modulating the BRM of large physiological and pathological bone defects.展开更多
Bone defect repairs are based on bone graft fusion or replacement.Current large bone defect treatments are inadequate and lack of reliable technology.Therefore,we aimed to investigate a simple technique using three-di...Bone defect repairs are based on bone graft fusion or replacement.Current large bone defect treatments are inadequate and lack of reliable technology.Therefore,we aimed to investigate a simple technique using three-dimensional(3D)-printed individualized porous implants without any bone grafts,osteoinductive agents,or surface biofunctionalization to treat large bone defects,and systematically study its long-term therapeutic effects and osseointegration characteristics.Twenty-six patients with large bone defects caused by tumor,infection,or trauma received treatment with individualized porous implants;among them,three typical cases underwent a detailed study.Additionally,a large segmental femur defect sheep model was used to study the osseointegration characteristics.Immediate and long-term biomechanical stability was achieved,and the animal study revealed that the bone grew into the pores with gradual remodeling,resulting in a long-term mechanically stable implant-bone complex.Advantages of 3D-printed microporous implants for the repair of bone defects included 1)that the stabilization devices were immediately designed and constructed to achieve early postoperative mobility,and 2)that osseointegration between the host bone and implants was achieved without bone grafting.Our osseointegration method,in which the“implant-bone”interface fusion concept was used instead of“bone-bone”fusion,subverts the traditional idea of osseointegration.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
文摘Additive manufacturing(AM)has revolutionized the design and manufacturing of patient-specific,three-dimensional(3D),complex porous structures known as scaffolds for tissue engineering applications.The use of advanced image acquisition techniques,image processing,and computer-aided design methods has enabled the precise design and additive manufacturing of anatomically correct and patient-specific implants and scaffolds.However,these sophisticated techniques can be timeconsuming,labor-intensive,and expensive.Moreover,the necessary imaging and manufacturing equipment may not be readily available when urgent treatment is needed for trauma patients.In this study,a novel design and AM methods are proposed for the development of modular and customizable scaffold blocks that can be adapted to fit the bone defect area of a patient.These modular scaffold blocks can be combined to quickly form any patient-specific scaffold directly from two-dimensional(2D)medical images when the surgeon lacks access to a 3D printer or cannot wait for lengthy 3D imaging,modeling,and 3D printing during surgery.The proposed method begins with developing a bone surface-modeling algorithm that reconstructs a model of the patient’s bone from 2D medical image measurements without the need for expensive 3D medical imaging or segmentation.This algorithm can generate both patient-specific and average bone models.Additionally,a biomimetic continuous path planning method is developed for the additive manufacturing of scaffolds,allowing porous scaffold blocks with the desired biomechanical properties to be manufactured directly from 2D data or images.The algorithms are implemented,and the designed scaffold blocks are 3D printed using an extrusion-based AM process.Guidelines and instructions are also provided to assist surgeons in assembling scaffold blocks for the self-repair of patient-specific large bone defects.
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This work is supported by National Key Research and Development Program of China(2016YFC1100600)the National Natural Science Foundation of China(81972058 and 81902194)the Multicenter Clinical Research Project of Shanghai Jiao Tong University School of Medicine(DLY201506).
文摘Complicated and large acetabular bone defects present the main challenges and difficulty in the revision of total hip arthroplasty(THA).This study aimed to explore the advantages of three-dimensional(3D)printing technology in the reconstruction of such acetabular bone defects.We retrospectively analyzed the prognosis of four severe bone defects around the acetabulum in three patients who were treated using 3D printing technology.Reconstruction of bone defect by conventional methods was difficult in these patients.In this endeavor,we used radiographic methods,related computer software such as Materialise's interactive medical image control system and Siemens NX software,and actual surgical experience to estimate defect volume,prosthesis stability,and installation accuracy,respectively.Moreover,a Harris hip score was obtained to evaluate limb function.It was found that bone defects could be adequately reconstructed using a 3D printing prosthesis,and its stability was reliable.The Harris hip score indicated a very good functional recovery in all three patients.In conclusion,3D printing technology had a good therapeutic effect on both complex and large bone defects in the revision of THA.It was able to achieve good curative effects in patients with large bone 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supported by the National Natural Science Foundation of China(No.31971271)。
文摘Bone is a complex biological tissue with a complicated hierarchical nanocomposite structure.The native microen-vironment of the bone tissue may be significantly disrupted by large physiological and pathological bone defects.Bone defects are often treated via complex surgical procedures that involve the application of autografts or al-lografts.While these grafting procedures often suffer from insufficient natural bone stock and immunorejection.Moreover,these traditional treatment methods fail to simulate a regenerative microenvironment,which plays a significant role in regeneration of bone tissue and repair of large bone defects.To this end,various biomimetic scaffolds have been devised to mimic the native microenvironment of bone and thereby to simultaneously re-pair bone defects and promote bone regeneration.We propose here a novel concept,in vivo bone regenerative microenvironment(BRM),which enables repair of large bone defects and enhances new bone tissue formation with external regulation.In this review,we mainly focus on materials and methods for fabrication of biomimetic scaffolds,as well as their therapeutic efficacy in modulating the BRM of large physiological and pathological bone defects.
基金the grant from the Ministry of Science and Technology of the People’s Republic of China(grant number 2016YFB1101501)Beijing Municipal Science&Technology Commission(Project Z181100001718195)。
文摘Bone defect repairs are based on bone graft fusion or replacement.Current large bone defect treatments are inadequate and lack of reliable technology.Therefore,we aimed to investigate a simple technique using three-dimensional(3D)-printed individualized porous implants without any bone grafts,osteoinductive agents,or surface biofunctionalization to treat large bone defects,and systematically study its long-term therapeutic effects and osseointegration characteristics.Twenty-six patients with large bone defects caused by tumor,infection,or trauma received treatment with individualized porous implants;among them,three typical cases underwent a detailed study.Additionally,a large segmental femur defect sheep model was used to study the osseointegration characteristics.Immediate and long-term biomechanical stability was achieved,and the animal study revealed that the bone grew into the pores with gradual remodeling,resulting in a long-term mechanically stable implant-bone complex.Advantages of 3D-printed microporous implants for the repair of bone defects included 1)that the stabilization devices were immediately designed and constructed to achieve early postoperative mobility,and 2)that osseointegration between the host bone and implants was achieved without bone grafting.Our osseointegration method,in which the“implant-bone”interface fusion concept was used instead of“bone-bone”fusion,subverts the traditional idea of osseointegration.
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.
