Additive manufacturing has received attention for the fabrication of medical implants that have customized and complicated structures.Biodegradable Zn metals are revolutionary materials for orthopedic implants.In this...Additive manufacturing has received attention for the fabrication of medical implants that have customized and complicated structures.Biodegradable Zn metals are revolutionary materials for orthopedic implants.In this study,pure Zn porous scaffolds with diamond structures were fabricated using customized laser powder bed fusion(L-PBF)technology.First,the mechanical properties,corrosion behavior,and biocompatibility of the pure Zn porous scaffolds were characterized in vitro.The scaffolds were then implanted into the rabbit femur critical-size bone defect model for 24 weeks.The results showed that the pure Zn porous scaffolds had compressive strength and rigidity comparable to those of cancellous bone,as well as relatively suitable degradation rates for bone regeneration.A benign host response was observed using hematoxylin and eosin(HE)staining of the heart,liver,spleen,lungs,and kidneys.Moreover,the pure Zn porous scaffold showed good biocompatibility and osteogenic promotion ability in vivo.This study showed that pure Zn porous scaffolds with customized structures fabricated using L-PBF represent a promising biodegradable solution for treating large bone defects.展开更多
A novel biodegradable metal system,ZnLiCa ternary alloys,were systematically investigated both in vitro and in vivo.The ultimate tensile strength(UTS)of Zn0.8Li0.1Ca alloy reached 567.60±9.56 MPa,which is compara...A novel biodegradable metal system,ZnLiCa ternary alloys,were systematically investigated both in vitro and in vivo.The ultimate tensile strength(UTS)of Zn0.8Li0.1Ca alloy reached 567.60±9.56 MPa,which is comparable to pure Ti,one of the most common material used in orthopedics.The elongation of Zn0.8Li0.1Ca is 27.82±18.35%,which is the highest among the ZnLiCa alloys.The in vitro degradation rate of Zn0.8Li0.1Ca alloy in simulated body fluid(SBF)showed significant acceleration than that of pure Zn.CCK-8 tests and hemocompatibility tests manifested that ZnLiCa alloys exhibit good biocompatibility.Real-time PCR showed that Zn0.8Li0.1Ca alloy successfully stimulated the expressions of osteogenesis-related genes(ALP,COL-1,OCN and Runx-2),especially the OCN.An in vivo implantation was conducted in the radius of New Zealand rabbits for 24 weeks,aiming to treat the bone defects.The Micro-CT and histological evaluations proved that the regeneration of bone defect was faster within the Zn0.8Li0.1Ca alloy scaffold than the pure Ti scaffold.Zn0.8Li0.1Ca alloy showed great potential to be applied in orthopedics,especially in the load-bearing sites.展开更多
Magnesium phosphate bone cements(MPC)have been recognized as a viable alternative for bone defect repair due to their high mechanical strength and biodegradability.However,their poor porosity and permeability limit os...Magnesium phosphate bone cements(MPC)have been recognized as a viable alternative for bone defect repair due to their high mechanical strength and biodegradability.However,their poor porosity and permeability limit osteogenic cell ingrowth and vascularization,which is critical for bone regeneration.In the current study,we constructed a novel hierarchically-porous magnesium phosphate bone cement by incorporating extracellular matrix(ECM)-mimicking electrospun silk fibroin(SF)nanofibers.The SF-embedded MPC(SM)exhibited a heterogeneous and hierarchical structure,which effectively facilitated the rapid infiltration of oxygen and nutrients as well as cell ingrowth.Besides,the SF fibers improved the mechanical properties of MPC and neutralized the highly alkaline environment caused by excess magnesium oxide.Bone marrow stem cells(BMSCs)adhered excellently on SM,as illustrated by formation of more pseudopodia.CCK8 assay showed that SM promoted early proliferation of BMSCs.Our study also verified that SM increased the expression of OPN,RUNX2 and BMP2,suggesting enhanced osteogenic differentiation of BMSCs.We screened for osteogenesis-related pathways,including FAK signaing,Wnt signaling and Notch signaling,and found that SM aided in the process of bone regeneration by suppressing the Notch signaling pathway,proved by the downregulation of NICD1,Hes1 and Hey2.In addition,using a bone defect model of rat calvaria,the study revealed that SM exhibited enhanced osteogenesis,bone ingrowth and vascularization compared with MPC alone.No adverse effect was found after implantation of SM in vivo.Overall,our novel SM exhibited promising prospects for the treatment of critical-sized bone defects.展开更多
The scarcity of native periosteum poses a significant clinical barrier in the repair of critical-sized bone defects.The challenge of enhancing regenerative potential in bone healing is further compounded by oxidative ...The scarcity of native periosteum poses a significant clinical barrier in the repair of critical-sized bone defects.The challenge of enhancing regenerative potential in bone healing is further compounded by oxidative stress at the fracture site.However,the introduction of artificial periosteum has demonstrated its ability to promote bone regeneration through the provision of appropriate mechanical support and controlled release of proosteogenic factors.In this study,a poly(L-lactic acid)(PLLA)/hyaluronic acid(HA)-based nanofibrous membrane was fabricated using the coaxial electrospinning technique.The incorporation of irisin into the core-shell structure of PLLA/HA nanofibers(PLLA/HA@Irisin)achieved its sustained release.In vitro experiments demonstrated that the PLLA/HA@Irisin membranes exhibited favorable biocompatibility.The osteogenic differentiation of bone marrow mesenchymal stem cells(BMMSCs)was improved by PLLA/HA@Irisin,as evidenced by a significant increase in alkaline phosphatase activity and matrix mineralization.Mechanistically,PLLA/HA@Irisin significantly enhanced the mitochondrial function of BMMSCs via the activation of the sirtuin 3 antioxidant pathway.To assess the therapeutic effectiveness,PLLA/HA@Irisin membranes were implanted in situ into critical-sized calvarial defects in rats.The results at 4 and 8 weeks post-surgery indicated that the implantation of PLLA/HA@Irisin exhibited superior efficacy in promoting vascularized bone formation,as demonstrated by the enhancement of bone matrix synthesis and the development of new blood vessels.The results of our study indicate that the electrospun PLLA/HA@Irisin nanofibers possess characteristics of a biomimetic periosteum,showing potential for effectively treating critical-sized bone defects by improving the mitochondrial function and maintaining redox homeostasis of BMMSCs.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
Critical size bone defects represent a significant challenge worldwide,often leading to persistent pain and physical disability that profoundly impact patients’quality of life and mental well-being.To address the int...Critical size bone defects represent a significant challenge worldwide,often leading to persistent pain and physical disability that profoundly impact patients’quality of life and mental well-being.To address the intricate and complex repair processes involved in these defects,we performed single-cell RNA sequencing and revealed notable shifts in cellular populations within regenerative tissue.Specifically,we observed a decrease in progenitor lineage cells and endothelial cells,coupled with an increase in fibrotic lineage cells and pro-inflammatory cells within regenerative tissue.Furthermore,our analysis of differentially expressed genes and associated signaling pathway at the single-cell level highlighted impaired angiogenesis as a central pathway in critical size bone defects,notably influenced by reduction of Spp1 and Cxcl12 expression.This deficiency was particularly pronounced in progenitor lineage cells and myeloid lineage cells,underscoring its significance in the regeneration process.In response to these findings,we developed an innovative approach to enhance bone regeneration in critical size bone defects.Our fabrication process involves the integration of electrospun PCL fibers with electrosprayed PLGA microspheres carrying Spp1 and Cxcl12.This design allows for the gradual release of Spp1 and Cxcl12 in vitro and in vivo.To evaluate the efficacy of our approach,we locally applied PCL scaffolds loaded with Spp1 and Cxcl12 in a murine model of critical size bone defects.Our results demonstrated restored angiogenesis,accelerated bone regeneration,alleviated pain responses and improved mobility in treated mice.展开更多
The healing of critical-sized bone defects(CSD)remains a challenge in orthopedic medicine.In recent years,scaffolds with sophisticated microstructures fabricated by the emerging three-dimensional(3D)printing technolog...The healing of critical-sized bone defects(CSD)remains a challenge in orthopedic medicine.In recent years,scaffolds with sophisticated microstructures fabricated by the emerging three-dimensional(3D)printing technology have lighted up the treatment of the CSD due to the elaborate microenvironments and support they may build.Here,we established a magnesium oxide-reinforced 3D-printed biocompos-ite scaffold to investigate the effect of magnesium-enriched 3D microenvironment on CSD repairing.The composite was prepared using a biodegradable polymer matrix,polycaprolactone(PCL),and the disper-sion phase,magnesium oxide(MgO).With the appropriate surface treatment by saline coupling agent,the MgO dispersed homogeneously in the polymer matrix,leading to enhanced mechanical performance and steady release of magnesium ion(Mg^(2+))for superior cytocompatibility,higher cell viability,advanced osteogenic differentiation,and cell mineralization capabilities in comparison with the pure PCL.The in-vivo femoral implantation and critical-sized cranial bone defect studies demonstrated the importance of the 3D magnesium microenvironment,as a scaffold that released appropriate Mg^(2+) exhibited remarkably increased bone volume,enhanced angiogenesis,and almost recovered CSD after 8-week implantation.Overall,this study suggests that the magnesium-enriched 3D scaffold is a potential candidate for the treatment of CSD in a cell-free therapeutic approach.展开更多
There is a continuing need for artificial bone substitutes for bone repair and reconstruction,Magnesium phosphate bone cement(MPC)has exceptional degradable properties and exhibits promising biocompatibility.However,i...There is a continuing need for artificial bone substitutes for bone repair and reconstruction,Magnesium phosphate bone cement(MPC)has exceptional degradable properties and exhibits promising biocompatibility.However,its mechanical strength needs improved and its low osteo-inductive potential limits its therapeutic application in bone regeneration.We functionally modified MPC by using a polymeric carboxymethyl chitosan-sodium alginate(CMCS/SA)gel network.This had the advantages of:improved compressive strength,ease of handling,and an optimized interface for bioactive bone in-growth.The new composites with 2%CMCS/SA showed the most favorable physicochemical properties,including mechanical strength,wash-out resistance,setting time,injectable time and heat release.Biologically,the composite promoted the attachment and proliferation of osteoblast cells.It was also found to induce osteogenic differentiation in vitro,as verified by expression of osteogenic markers.In terms of molecular mechanisms,data showed that new bone cement activated the Wnt pathway through inhibition of the phosphorylation ofβ-catenin,which is dependent on focal adhesion kinase.Through micro-computed tomography and histological analysis,we found that the MPC-CMCS/SA scaffolds,compared with MPC alone,showed increased bone regeneration in a rat calvarial defect model.Overall,our study suggested that the novel composite had potential to help repair critical bone defects in clinical practice.展开更多
Recently, porous titanium granules （PTGs） have been indicated for the preservation of the dimensions of post-extraction sockets, as a filler in sinus lift procedures and for the treatment of peri-implant and periodo...Recently, porous titanium granules （PTGs） have been indicated for the preservation of the dimensions of post-extraction sockets, as a filler in sinus lift procedures and for the treatment of peri-implant and periodontal defects, based on the osteoconductivity and dimensional stability of the titanium granules. However, there is a lack of information regarding the use of this material in larger defects and in conjunction with membranes. The objective of this study is to test the behavior of PTGs used to fill critical size defects in rabbit tibiae, with and without membranes. Critical defects were created in both tibiae of rabbits, divided randomly into three groups： Group A （defect filled with PTG）, Group B （defect filled with PTG＋collagen membrane） and a control group （empty defect）. After six weeks, histomorphometric analysis was performed. The results showed more defect closures at the cortical area （87.37%±2.2%） and more bone formation at the marrow area （57.6%± 1.3%） in Group B, in comparison with the other groups （P〈0.05）; the use of membranes improved the material stability expressed as more percentages of the original material when membranes were used （P〈0.05）. Finally, inflammatory reactions were observed when the granules were not protected by membranes. In spite of the limitations of this animal study, it may be concluded that PTG particles are osteoconductive and allow bone growth. The PTG particles must be covered by a membrane, especially when grafting larger defects, in order to control particle migration, promote clot stabilization and separate the PTG graft from undesired soft tissue cells.展开更多
Next-generation synthetic bone graft therapies will most likely be composed of resorbable polymers in combination with bioactive components.In this article,we continue our exploration of E1001(1k),a tyrosine-derived p...Next-generation synthetic bone graft therapies will most likely be composed of resorbable polymers in combination with bioactive components.In this article,we continue our exploration of E1001(1k),a tyrosine-derived polycarbonate,as an orthopedic implant material.Specifically,we use E1001(1k),which is degradable,nontoxic,and osteoconductive,to fabricate porous bone regeneration scaffolds that were enhanced by two different types of calcium phosphate(CP)coatings:in one case,pure dicalcium phosphate dihydrate was precipitated on the scaffold surface and throughout its porous structure(E1001(1k)+CP).In the other case,bone matrix minerals(BMM)such as zinc,manganese and fluoride were co-precipitated within the dicalcium phosphate dihydrate coating(E1001(1k)+BMM).These scaffold compositions were compared against each other and against ChronOS(Synthes USA,West Chester,PA,USA),a clinically used bone graft substitute(BGS),which served as the positive control in our experimental design.This BGS is composed of poly(lactide co-e-caprolactone)and beta-tricalcium phosphate.We used the established rabbit calvaria critical-sized defect model to determine bone regeneration within the defect for each of the three scaffold compositions.New bone formation was determined after 2,4,6,8 and 12 weeks by micro-computerized tomography(mCT)and histology.The experimental tyrosine-derived polycarbonate,enhanced with dicalcium phosphate dihydrate,E1001(1k)+CP,supported significant bone formation within the defects and was superior to the same scaffold containing a mix of BMM,E1001(1k)+BMM.The comparison with the commercially available BGS was complicated by the large variability in bone formation observed for the laboratory preparations of E1001(1k)scaffolds.At all time points,there was a trend for E1001(1k)+CP to be superior to the commercial BGS.However,only at the 6-week time point did this trend reach statistical significance.Detailed analysis of the μCT data suggested an increase in bone formation from 2 through 12 weeks in implant site展开更多
基金supported by the National Key R&D Program of China[grant number 2018YFE0104200]the National Natural Science Foundation of China[grant numbers 51901003,51931001,52171233,51875310]+1 种基金the Beijing Natural Science Foundation[grant number L212014]the Open Project of NMPA Key Laboratory for Dental Materials[grant number PKUSS20200401].
文摘Additive manufacturing has received attention for the fabrication of medical implants that have customized and complicated structures.Biodegradable Zn metals are revolutionary materials for orthopedic implants.In this study,pure Zn porous scaffolds with diamond structures were fabricated using customized laser powder bed fusion(L-PBF)technology.First,the mechanical properties,corrosion behavior,and biocompatibility of the pure Zn porous scaffolds were characterized in vitro.The scaffolds were then implanted into the rabbit femur critical-size bone defect model for 24 weeks.The results showed that the pure Zn porous scaffolds had compressive strength and rigidity comparable to those of cancellous bone,as well as relatively suitable degradation rates for bone regeneration.A benign host response was observed using hematoxylin and eosin(HE)staining of the heart,liver,spleen,lungs,and kidneys.Moreover,the pure Zn porous scaffold showed good biocompatibility and osteogenic promotion ability in vivo.This study showed that pure Zn porous scaffolds with customized structures fabricated using L-PBF represent a promising biodegradable solution for treating large bone defects.
基金National Natural Science Foundation of China(Grant No.51931001)International Cooperation and Exchange project between NSFC(China)and CNR(Italy)(NSFC-CNR Grant No.52011530392).
文摘A novel biodegradable metal system,ZnLiCa ternary alloys,were systematically investigated both in vitro and in vivo.The ultimate tensile strength(UTS)of Zn0.8Li0.1Ca alloy reached 567.60±9.56 MPa,which is comparable to pure Ti,one of the most common material used in orthopedics.The elongation of Zn0.8Li0.1Ca is 27.82±18.35%,which is the highest among the ZnLiCa alloys.The in vitro degradation rate of Zn0.8Li0.1Ca alloy in simulated body fluid(SBF)showed significant acceleration than that of pure Zn.CCK-8 tests and hemocompatibility tests manifested that ZnLiCa alloys exhibit good biocompatibility.Real-time PCR showed that Zn0.8Li0.1Ca alloy successfully stimulated the expressions of osteogenesis-related genes(ALP,COL-1,OCN and Runx-2),especially the OCN.An in vivo implantation was conducted in the radius of New Zealand rabbits for 24 weeks,aiming to treat the bone defects.The Micro-CT and histological evaluations proved that the regeneration of bone defect was faster within the Zn0.8Li0.1Ca alloy scaffold than the pure Ti scaffold.Zn0.8Li0.1Ca alloy showed great potential to be applied in orthopedics,especially in the load-bearing sites.
基金support of the Provincial Key Resaearch and Development Program of Hubei,China (No.2020BCB058)Youth Science and Technology Talent Project of Hubei Province (2023DJC163).
文摘Magnesium phosphate bone cements(MPC)have been recognized as a viable alternative for bone defect repair due to their high mechanical strength and biodegradability.However,their poor porosity and permeability limit osteogenic cell ingrowth and vascularization,which is critical for bone regeneration.In the current study,we constructed a novel hierarchically-porous magnesium phosphate bone cement by incorporating extracellular matrix(ECM)-mimicking electrospun silk fibroin(SF)nanofibers.The SF-embedded MPC(SM)exhibited a heterogeneous and hierarchical structure,which effectively facilitated the rapid infiltration of oxygen and nutrients as well as cell ingrowth.Besides,the SF fibers improved the mechanical properties of MPC and neutralized the highly alkaline environment caused by excess magnesium oxide.Bone marrow stem cells(BMSCs)adhered excellently on SM,as illustrated by formation of more pseudopodia.CCK8 assay showed that SM promoted early proliferation of BMSCs.Our study also verified that SM increased the expression of OPN,RUNX2 and BMP2,suggesting enhanced osteogenic differentiation of BMSCs.We screened for osteogenesis-related pathways,including FAK signaing,Wnt signaling and Notch signaling,and found that SM aided in the process of bone regeneration by suppressing the Notch signaling pathway,proved by the downregulation of NICD1,Hes1 and Hey2.In addition,using a bone defect model of rat calvaria,the study revealed that SM exhibited enhanced osteogenesis,bone ingrowth and vascularization compared with MPC alone.No adverse effect was found after implantation of SM in vivo.Overall,our novel SM exhibited promising prospects for the treatment of critical-sized bone defects.
基金supported by the Natural Science Foundation of Jiangsu Province(BK20220046)Key Laboratory of Orthopaedics of Suzhou(SZS2022017)the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD).
文摘The scarcity of native periosteum poses a significant clinical barrier in the repair of critical-sized bone defects.The challenge of enhancing regenerative potential in bone healing is further compounded by oxidative stress at the fracture site.However,the introduction of artificial periosteum has demonstrated its ability to promote bone regeneration through the provision of appropriate mechanical support and controlled release of proosteogenic factors.In this study,a poly(L-lactic acid)(PLLA)/hyaluronic acid(HA)-based nanofibrous membrane was fabricated using the coaxial electrospinning technique.The incorporation of irisin into the core-shell structure of PLLA/HA nanofibers(PLLA/HA@Irisin)achieved its sustained release.In vitro experiments demonstrated that the PLLA/HA@Irisin membranes exhibited favorable biocompatibility.The osteogenic differentiation of bone marrow mesenchymal stem cells(BMMSCs)was improved by PLLA/HA@Irisin,as evidenced by a significant increase in alkaline phosphatase activity and matrix mineralization.Mechanistically,PLLA/HA@Irisin significantly enhanced the mitochondrial function of BMMSCs via the activation of the sirtuin 3 antioxidant pathway.To assess the therapeutic effectiveness,PLLA/HA@Irisin membranes were implanted in situ into critical-sized calvarial defects in rats.The results at 4 and 8 weeks post-surgery indicated that the implantation of PLLA/HA@Irisin exhibited superior efficacy in promoting vascularized bone formation,as demonstrated by the enhancement of bone matrix synthesis and the development of new blood vessels.The results of our study indicate that the electrospun PLLA/HA@Irisin nanofibers possess characteristics of a biomimetic periosteum,showing potential for effectively treating critical-sized bone defects by improving the mitochondrial function and maintaining redox homeostasis of BMMSCs.
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.
基金supported by the following NIH grants:R01 grants(AR075860,AR077616,and AR083900 to JSHL138175,HL164062,and DK133949 to JG)and a R21 grant(AR077226 to JS)a P30 Core Center grant(AR074992 to the Musculoskeletal Research Center at Washington University in St.Louis).
文摘Critical size bone defects represent a significant challenge worldwide,often leading to persistent pain and physical disability that profoundly impact patients’quality of life and mental well-being.To address the intricate and complex repair processes involved in these defects,we performed single-cell RNA sequencing and revealed notable shifts in cellular populations within regenerative tissue.Specifically,we observed a decrease in progenitor lineage cells and endothelial cells,coupled with an increase in fibrotic lineage cells and pro-inflammatory cells within regenerative tissue.Furthermore,our analysis of differentially expressed genes and associated signaling pathway at the single-cell level highlighted impaired angiogenesis as a central pathway in critical size bone defects,notably influenced by reduction of Spp1 and Cxcl12 expression.This deficiency was particularly pronounced in progenitor lineage cells and myeloid lineage cells,underscoring its significance in the regeneration process.In response to these findings,we developed an innovative approach to enhance bone regeneration in critical size bone defects.Our fabrication process involves the integration of electrospun PCL fibers with electrosprayed PLGA microspheres carrying Spp1 and Cxcl12.This design allows for the gradual release of Spp1 and Cxcl12 in vitro and in vivo.To evaluate the efficacy of our approach,we locally applied PCL scaffolds loaded with Spp1 and Cxcl12 in a murine model of critical size bone defects.Our results demonstrated restored angiogenesis,accelerated bone regeneration,alleviated pain responses and improved mobility in treated mice.
基金The authors would like to thank Li LI and H.Z.Xie for the technical support.This work was financially supported by the National Natural Science Foundation of China(Nos.82002303 and 81702171)the Guangdong Basic and Applied Basic Research Foundation(Nos.2022A1515011536,2021A1515220093,2021A1515220086,2019A1515111156,and 2022A1515011815)+7 种基金the Scientific Research Foundation of Peking University Shenzhen hospital(No.KYQD2021064)the Health and Medical Research Fund(No.19180712)the Shenzhen Double Chain Project for Innovation and Development Industry supported by the Bureau of Industry and Information Technology of Shenzhen(No.201806081018272960)the Shenzhen Science and Technology Innovation Committee Projects(Nos.JCYJ20190809182213535 and JSGG20180507183242702)the program from Shanghai Municipal Health Commission(No.201740165)the National Key R&D Program of China(No.2018YFC1105100)the Hong Kong Innovation Technology Fund(Nos.ITS/287/17 and ITS/405/18)the Hong Kong Research Grant Council General Research Fund(No.17214516).
文摘The healing of critical-sized bone defects(CSD)remains a challenge in orthopedic medicine.In recent years,scaffolds with sophisticated microstructures fabricated by the emerging three-dimensional(3D)printing technology have lighted up the treatment of the CSD due to the elaborate microenvironments and support they may build.Here,we established a magnesium oxide-reinforced 3D-printed biocompos-ite scaffold to investigate the effect of magnesium-enriched 3D microenvironment on CSD repairing.The composite was prepared using a biodegradable polymer matrix,polycaprolactone(PCL),and the disper-sion phase,magnesium oxide(MgO).With the appropriate surface treatment by saline coupling agent,the MgO dispersed homogeneously in the polymer matrix,leading to enhanced mechanical performance and steady release of magnesium ion(Mg^(2+))for superior cytocompatibility,higher cell viability,advanced osteogenic differentiation,and cell mineralization capabilities in comparison with the pure PCL.The in-vivo femoral implantation and critical-sized cranial bone defect studies demonstrated the importance of the 3D magnesium microenvironment,as a scaffold that released appropriate Mg^(2+) exhibited remarkably increased bone volume,enhanced angiogenesis,and almost recovered CSD after 8-week implantation.Overall,this study suggests that the magnesium-enriched 3D scaffold is a potential candidate for the treatment of CSD in a cell-free therapeutic approach.
基金support of the National Natural Science Foundation of China(No.81802689,51772233)the Provincial Key Research and Development Program of Hubei,China(No.2020BCB058)+2 种基金State Key Laboratory of Advanced Technology for Materials Synthesis and Processing(Wuhan University of Technology)(2021-KF-22)the Major Special Projects of Technological Innovation of Hubei Province(No.2019ACA130)the Application Foundation and Front Research Program of Wuhan(No.2018010401011273).
文摘There is a continuing need for artificial bone substitutes for bone repair and reconstruction,Magnesium phosphate bone cement(MPC)has exceptional degradable properties and exhibits promising biocompatibility.However,its mechanical strength needs improved and its low osteo-inductive potential limits its therapeutic application in bone regeneration.We functionally modified MPC by using a polymeric carboxymethyl chitosan-sodium alginate(CMCS/SA)gel network.This had the advantages of:improved compressive strength,ease of handling,and an optimized interface for bioactive bone in-growth.The new composites with 2%CMCS/SA showed the most favorable physicochemical properties,including mechanical strength,wash-out resistance,setting time,injectable time and heat release.Biologically,the composite promoted the attachment and proliferation of osteoblast cells.It was also found to induce osteogenic differentiation in vitro,as verified by expression of osteogenic markers.In terms of molecular mechanisms,data showed that new bone cement activated the Wnt pathway through inhibition of the phosphorylation ofβ-catenin,which is dependent on focal adhesion kinase.Through micro-computed tomography and histological analysis,we found that the MPC-CMCS/SA scaffolds,compared with MPC alone,showed increased bone regeneration in a rat calvarial defect model.Overall,our study suggested that the novel composite had potential to help repair critical bone defects in clinical practice.
文摘Recently, porous titanium granules （PTGs） have been indicated for the preservation of the dimensions of post-extraction sockets, as a filler in sinus lift procedures and for the treatment of peri-implant and periodontal defects, based on the osteoconductivity and dimensional stability of the titanium granules. However, there is a lack of information regarding the use of this material in larger defects and in conjunction with membranes. The objective of this study is to test the behavior of PTGs used to fill critical size defects in rabbit tibiae, with and without membranes. Critical defects were created in both tibiae of rabbits, divided randomly into three groups： Group A （defect filled with PTG）, Group B （defect filled with PTG＋collagen membrane） and a control group （empty defect）. After six weeks, histomorphometric analysis was performed. The results showed more defect closures at the cortical area （87.37%±2.2%） and more bone formation at the marrow area （57.6%± 1.3%） in Group B, in comparison with the other groups （P〈0.05）; the use of membranes improved the material stability expressed as more percentages of the original material when membranes were used （P〈0.05）. Finally, inflammatory reactions were observed when the granules were not protected by membranes. In spite of the limitations of this animal study, it may be concluded that PTG particles are osteoconductive and allow bone growth. The PTG particles must be covered by a membrane, especially when grafting larger defects, in order to control particle migration, promote clot stabilization and separate the PTG graft from undesired soft tissue cells.
基金This research was sponsored by the Armed Forces Institute of Regenerative Medicine(AFIRM)award number W81XWH-08-2-0034The US Army Medical Research Acquisition Activity,820 Chandler Street,Fort Detrick MD 21702-5014 is the awarding and administering acquisition office。
文摘Next-generation synthetic bone graft therapies will most likely be composed of resorbable polymers in combination with bioactive components.In this article,we continue our exploration of E1001(1k),a tyrosine-derived polycarbonate,as an orthopedic implant material.Specifically,we use E1001(1k),which is degradable,nontoxic,and osteoconductive,to fabricate porous bone regeneration scaffolds that were enhanced by two different types of calcium phosphate(CP)coatings:in one case,pure dicalcium phosphate dihydrate was precipitated on the scaffold surface and throughout its porous structure(E1001(1k)+CP).In the other case,bone matrix minerals(BMM)such as zinc,manganese and fluoride were co-precipitated within the dicalcium phosphate dihydrate coating(E1001(1k)+BMM).These scaffold compositions were compared against each other and against ChronOS(Synthes USA,West Chester,PA,USA),a clinically used bone graft substitute(BGS),which served as the positive control in our experimental design.This BGS is composed of poly(lactide co-e-caprolactone)and beta-tricalcium phosphate.We used the established rabbit calvaria critical-sized defect model to determine bone regeneration within the defect for each of the three scaffold compositions.New bone formation was determined after 2,4,6,8 and 12 weeks by micro-computerized tomography(mCT)and histology.The experimental tyrosine-derived polycarbonate,enhanced with dicalcium phosphate dihydrate,E1001(1k)+CP,supported significant bone formation within the defects and was superior to the same scaffold containing a mix of BMM,E1001(1k)+BMM.The comparison with the commercially available BGS was complicated by the large variability in bone formation observed for the laboratory preparations of E1001(1k)scaffolds.At all time points,there was a trend for E1001(1k)+CP to be superior to the commercial BGS.However,only at the 6-week time point did this trend reach statistical significance.Detailed analysis of the μCT data suggested an increase in bone formation from 2 through 12 weeks in implant site
