Biphasic calcium phosphate (BCP) powders were prepared by hydrolyzation proc-ess and surface-modified by directly grafted L-lactide (LLA) onto the surface of BCP through a chemical linkage. The grafting ratio of o...Biphasic calcium phosphate (BCP) powders were prepared by hydrolyzation proc-ess and surface-modified by directly grafted L-lactide (LLA) onto the surface of BCP through a chemical linkage. The grafting ratio of organic groups was 9 wt%. After surface modification, the surface of BCP powders was covered by the lamella-shaped crystal. Poly (L-lactide) was mixed with BCP to form the BCP/PLLA biocomposite. Modified BCP (mBCP) particles could be uniformly dis-persed in PLLA matrix. The compressive strength of the mBCP/PLLA composite is 115 MPa, 28% higher than that of unmodified-BCP/PLLA composite. The improved mechanical strength is attributed to the enhanced adhesion between the inorganic BCP filler and the organic PLLA matrix.展开更多
Biphasic calcium phosphate (BCP) consisting of hydroxyapatite (HA) and β-tricalcium phosphate (β-TCP) was successfully synthesized by new hydrothermal route using β-TCP as precursor. The X-ray diffraction analysis ...Biphasic calcium phosphate (BCP) consisting of hydroxyapatite (HA) and β-tricalcium phosphate (β-TCP) was successfully synthesized by new hydrothermal route using β-TCP as precursor. The X-ray diffraction analysis of as-synthesized powder indicated that β-TCP had been transformed into HA phase and amount of HA formed gradually increased with prolonged time. The results revealed that the recent technique may be able to control the composition of the obtained BCP which would influence the bioresorbability. Porous body of BCP was prepared by impregnation of polymeric sponge template with the slurry of the powder followed by sintering. The X-ray diffraction of porous product revealed that the composition of β-TCP increased after sintering indicating that HA had been decomposed. Porous BCP obtained from the recent technique possessed both macro and micropores structure which are useful for rapid tissue formation. Besides, the recent porous fabrication technique yielded porous BCP which preserved the sponge template morphology, enabling it to fabricate porous material with controlled pores structure.展开更多
Incorporation of trace elements into calcium phosphate structure is of great interest for the development of artificial bone implants. Biphasic calcium phosphate (BCP) composed of hydroxyapatite (HA) and β-tricalcium...Incorporation of trace elements into calcium phosphate structure is of great interest for the development of artificial bone implants. Biphasic calcium phosphate (BCP) composed of hydroxyapatite (HA) and β-tricalcium phosphate (β-TCP) have been synthesized in the presence of magnesium (5 M% - 20 M%) by gel method under physiological conditions. Crystallization of Mg-BCP in the gel medium mimics the Mg intake in the human body. Powder X-ray dif- fraction and Fourier transform infrared analyses confirmed that the Mg doping leads to the enrichment of β-TCP phase and suppresses the HA content in BCP. Nanoindentation studies indicate a significant decrease in hardness and elastic modulus values of BCP due to Mg doping. In vitro bioactivity study has confirmed the formation of apatite layer on the Mg doped samples making it suitable for bone replacement. The results suggest that the optimum Mg doping promotes the bioactivity which is perquisite for biomedical applications.展开更多
Current calcium phosphate ( CaP ) biomaterials for bone repair, substitution, augmentation and regeneration include hydroxyapatite ( HA ) from synthetic or biologic origin, beta-tricaicium phosphate ( β- TCP ),...Current calcium phosphate ( CaP ) biomaterials for bone repair, substitution, augmentation and regeneration include hydroxyapatite ( HA ) from synthetic or biologic origin, beta-tricaicium phosphate ( β- TCP ), biphasic calcium phosphate (BCP), and are available as granules, porous blocks, components of compashes (CaP/pollymer) cements, and as coatings on orthopedic and dental implants. Experimental calcium phosphate biomaterials include CO3^- and F-substituted apatites, Mg-and Zn-substituted β-TCP, calcium phosphate glasses, This paper is a brief review of the different types of CaP biomaterials and their properties such as bioactivity , osteoconductivity , osteoinductivity.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
The biocompatibility of surface-modified biphasic calcium phosphate (mBCP)/poly-L-Lactide (PLLA) biocomposite was investigated through a series of experiments in vitro and in vivo. Acute toxicity and short term sy...The biocompatibility of surface-modified biphasic calcium phosphate (mBCP)/poly-L-Lactide (PLLA) biocomposite was investigated through a series of experiments in vitro and in vivo. Acute toxicity and short term systemic toxicity experiments revealed no toxicity of the materials. Hemolysis assay indicated the good blood compatibility of the composite. In cytotoxicity assay, L929 mouse fibroblasts could well differentiate and proliferate. Animal experiments in vivo were.performed by implanting the materials into rabbits muscle for 8 weeks. The decreasing of inflammatory cells, the building of fibrous tissue layer as well as the growing of blood cells into materials indicated the nontoxicity of the composite. Based on the experiment results, surfacemodified BCP/PLLA biocomposite is proven to have superior biocompatibility, which would be a promising bone repairing material.展开更多
Magnesium(Mg^2+))ion plays important roles in biomineralization of bone,teeth and calcium carbonate skeletons.Herein,chicken eggshells mainly comprising of Mg-calcite nanocrystals(Mg/(Mg+Ca)2.0 mol.%)were used to fabr...Magnesium(Mg^2+))ion plays important roles in biomineralization of bone,teeth and calcium carbonate skeletons.Herein,chicken eggshells mainly comprising of Mg-calcite nanocrystals(Mg/(Mg+Ca)2.0 mol.%)were used to fabricate biphasic calcium phosphate(BCP),a mixture of hydroxyapatite(HA)and p-tricalcium phosphate(p-TCP)nanocrystals,through hydrothermal reactions at 200℃for 24 h.Our results indicated thatβ-TCP nanocrystals formed through the ion-exchange reactions of Mg-calcite,while HA nanocrystals were mainly produced by dissolution-reprecipitation reactions on the surfaces of eggshell samples in the hydrothermal system.Mg substitution in calcite resulted in formation ofβ-TCP nanocrystals instead of HA crystals through ion-exchange reactions.BCP samples with different compositions(28.6-77.8 wt.%β-TCP)were produced by controlling particle sizes of eggshells for hydrothermal reactions.The larger particles lead to the larger proportion ofβ-TCP in the BCP composition.Therefore,Mg substitution and particle size had synergetic effects on the hydrothermal synthesis of BCP using chicken eggshells through balance of ion-exchange and dissolution-reprecipitation reactions.Cell culture results showed that the BCP products were non-cytotoxic to MC3 T3-E1 cells,which may be used for bone substitute materials in future.展开更多
The combination between biphasic calcium phosphate(BCP)and the osteomimetic porous microstructure obtained via freeze casting is hoped to achieve excellent bone regeneration,while the effects of HA and b-TCP ratio cha...The combination between biphasic calcium phosphate(BCP)and the osteomimetic porous microstructure obtained via freeze casting is hoped to achieve excellent bone regeneration,while the effects of HA and b-TCP ratio changes on the degradation and biological performance of the BCP scaffolds with this unique microstructure need to be determined.Here,we prepared the osteomimetic BCP scaffolds with different HA/b-TCP ratios(HA30/b-TCP70,HA50/b-TCP50,HA70/b-TCP30)and the effects of different HA/b-TCPHA/b-TCP ratios on the degradation and biological performance were studied in vitro and vivo.These BCP scaffolds with different HA/b-TCP ratios exhibited similar microstructure,mechanical performance,and protein absorption capability,while HA70/b-TCP30 BCP scaffolds showed an advisable degradation rate.Study in vitro confirmed the bio-compatibility and promotion on the proliferation,differentiation of MG63 cells in the porous osteomimetic BCP scaffolds with a HA/b-TCP ratio at 30:70.Implantation experiments also showed that the porous osteomimetic BCP scaffolds with a HA/b-TCP ratio at 30:70 had excellent bone regeneration capacity and proper degradation rate compatible with bone growth.These results reveal that the porous osteomimetic BCP scaffold with a HA/b-TCP ratio at 30:70 is a potential candidate of biodegradable bone substitutes used for bone repair.展开更多
Background Bone grafting is commonly used to repair bone defects.As the porosity of the graft scaffold increases,bone formation increases,but the strength decreases.Early attempts to engineer materials were not able t...Background Bone grafting is commonly used to repair bone defects.As the porosity of the graft scaffold increases,bone formation increases,but the strength decreases.Early attempts to engineer materials were not able to resolve this problem.In recent years,nanomaterials have demonstrated the unique ability to improve the material strength and toughness while stimulating new bone formation.In our previous studies,we synthesized a nano-scale material by reinforcing a porous β-tricalcium phosphate (β-TCP) ceramic scaffold with Na2O-MgO-P2O5-CaO bioglass (β-TCP/BG).However,the in vivo effects of the β-TCP/BG scaffold on bone repair remain unknown.Methods We investigated the efficacy of β-TCP/BG scaffolds compared to autografts in a canine tibioflbula defect model.The tibioflbula defects were created in the right legs of 12 dogs,which were randomly assigned to either the scaffold group or the autograft group (six dogs per group).Radiographic evaluation was performed at 0,4,8,and 12 weeks post-surgery.The involved tibias were extracted at 12 weeks and were tested to failure via a three-point bending.After the biomechanical analysis,specimens were subsequently processed for scanning electron microscopy analysis and histological evaluations.Results Radiographic evaluation at 12 weeks post-operation revealed many newly formed osseous calluses and bony unions in both groups.Both the maximum force and break force in the scaffold group (n=6) were comparable to those in the autograft group (n=6,P >0.05),suggesting that the tissue-engineered bone repair achieved similar biomechanical properties to autograft bone repair.At 12 weeks post-operation,obvious new bone and blood vessel formations were observed in the artificial bone of the experimental group.Conclusions The results demonstrated that new bone formation and high bone strength were achieved in the β-TCP/ BG scaffold group,and suggested that the β-TCP/BG scaffold could be used as a synthetic alternative to autografts for the repair of bone defects.展开更多
Immune systems play a critical role in the regulation of bone formation and homeostasis,which arouses a growing interest in the development of biomaterials that can modulate both immune response and osteogenesis.In th...Immune systems play a critical role in the regulation of bone formation and homeostasis,which arouses a growing interest in the development of biomaterials that can modulate both immune response and osteogenesis.In this study,biphasic calcium phosphate(BCP)ceramics were modified with different whiskered surface,and their effects on macrophage polarization and functional status were investigated.The results showed that compared to BCP-W ceramics with long and solid whiskers,BCPHW ceramics with short and hollow whiskers surface were conducive to protein adsorption and macrophage elongation.Furthermore,BCP-HW ceramics down-regulated the expression of M1 macrophage markers(Il1β,Tnfα,and iNos),promoted the expression of M2 macrophage markers(Il10 and Arg)and growth factors(Tgfβ1 and Bmp2),which might be attributed to the differential integrin expression regulated by different whisker structures.The conditioned medium derived from the supernatant of macrophage/whiskered ceramic co-culture was further used to culture MC3T3-E1 pre-osteoblasts to evaluate the effects of whiskered ceramic-mediated macrophage secretion on osteogenesis in vitro.Compared with BCP-W ones,the secretion pattern induced by BCP-HW ceramics could promote the expression of bone markers in pre-osteoblasts,which might due to the activation of intracellular signaling cascades like BMP/Smad and TGF-β/Smad signaling pathways.A murine intramuscular implantation model suggested that after implantation for 1,2,and 3 weeks,BCP-HW ceramics drove the switch of macrophages to ARG+wound-healing M2 phenotype,while BCP-W ceramics increased the proportion of iNOS+M1 inflammatory macrophages.At 2 months,only BCP-HW could induce ectopic bone formation.Taken together,these results indicated that BCP ceramics with hollow whiskers were capable of creating a proper inflammatory microenvironment to induce bone formation.These whiskered BCP ceramics with good osteo-immunomodulatory capacity hold promise in serving as bone grafts to achieve desired bone repair and regeneration.展开更多
How to endow bone grafts with long-term antibacterial activity and good bone regenerative ability to achieve the regenerative repair of infected bone defects has been the focus of the clinical treatment of osteomyelit...How to endow bone grafts with long-term antibacterial activity and good bone regenerative ability to achieve the regenerative repair of infected bone defects has been the focus of the clinical treatment of osteomyelitis.The present study introduced a novel one-step route to realizing the co-doping of zinc oxide(ZnO)and zinc ion(Zn^(2+))in biphasic calcium phosphate(BCP)ceramics to utilize their synergistic antibacterial.Compared with the conventional BCP ceramics(BCP-Ca),the ZnO/Zn^(2+)co-doping ones(BCP-Zn)possessed strong antibacterial ability on E.coli and S.aureus as well as stimulated the osteogenic differentiation of bone marrow mesenchymal stem cells(BMSCs)effectively.The synergistic antibacterial mechanism of ZnO and Zn^(2+)was also investigated.BCP-Zn showed excellent osteoinductivity and angiogenesis at three months postoperatively in the canine intramuscular implantation model.Moreover,BCP-Zn exhibited excellent anti-infective ability and bone regenerative repair compared to BCP-Ca and control groups in the infected bone defect model of rat femur.Collectively,these findings suggest that the simultaneous introduction of ZnO/Zn^(2+)could have immense potential to expand the application of osteoinductive BCP ceramics in the regenerative repair of infected bone defects.展开更多
基金Funded by the Research Fund for the Doctoral Program of Higher Education of China (No. 20060610024)
文摘Biphasic calcium phosphate (BCP) powders were prepared by hydrolyzation proc-ess and surface-modified by directly grafted L-lactide (LLA) onto the surface of BCP through a chemical linkage. The grafting ratio of organic groups was 9 wt%. After surface modification, the surface of BCP powders was covered by the lamella-shaped crystal. Poly (L-lactide) was mixed with BCP to form the BCP/PLLA biocomposite. Modified BCP (mBCP) particles could be uniformly dis-persed in PLLA matrix. The compressive strength of the mBCP/PLLA composite is 115 MPa, 28% higher than that of unmodified-BCP/PLLA composite. The improved mechanical strength is attributed to the enhanced adhesion between the inorganic BCP filler and the organic PLLA matrix.
文摘Biphasic calcium phosphate (BCP) consisting of hydroxyapatite (HA) and β-tricalcium phosphate (β-TCP) was successfully synthesized by new hydrothermal route using β-TCP as precursor. The X-ray diffraction analysis of as-synthesized powder indicated that β-TCP had been transformed into HA phase and amount of HA formed gradually increased with prolonged time. The results revealed that the recent technique may be able to control the composition of the obtained BCP which would influence the bioresorbability. Porous body of BCP was prepared by impregnation of polymeric sponge template with the slurry of the powder followed by sintering. The X-ray diffraction of porous product revealed that the composition of β-TCP increased after sintering indicating that HA had been decomposed. Porous BCP obtained from the recent technique possessed both macro and micropores structure which are useful for rapid tissue formation. Besides, the recent porous fabrication technique yielded porous BCP which preserved the sponge template morphology, enabling it to fabricate porous material with controlled pores structure.
文摘Incorporation of trace elements into calcium phosphate structure is of great interest for the development of artificial bone implants. Biphasic calcium phosphate (BCP) composed of hydroxyapatite (HA) and β-tricalcium phosphate (β-TCP) have been synthesized in the presence of magnesium (5 M% - 20 M%) by gel method under physiological conditions. Crystallization of Mg-BCP in the gel medium mimics the Mg intake in the human body. Powder X-ray dif- fraction and Fourier transform infrared analyses confirmed that the Mg doping leads to the enrichment of β-TCP phase and suppresses the HA content in BCP. Nanoindentation studies indicate a significant decrease in hardness and elastic modulus values of BCP due to Mg doping. In vitro bioactivity study has confirmed the formation of apatite layer on the Mg doped samples making it suitable for bone replacement. The results suggest that the optimum Mg doping promotes the bioactivity which is perquisite for biomedical applications.
文摘Current calcium phosphate ( CaP ) biomaterials for bone repair, substitution, augmentation and regeneration include hydroxyapatite ( HA ) from synthetic or biologic origin, beta-tricaicium phosphate ( β- TCP ), biphasic calcium phosphate (BCP), and are available as granules, porous blocks, components of compashes (CaP/pollymer) cements, and as coatings on orthopedic and dental implants. Experimental calcium phosphate biomaterials include CO3^- and F-substituted apatites, Mg-and Zn-substituted β-TCP, calcium phosphate glasses, This paper is a brief review of the different types of CaP biomaterials and their properties such as bioactivity , osteoconductivity , osteoinductivity.
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.
基金supported by Doctoral Fund of Ministry of Education of China under grant No.20060610024
文摘The biocompatibility of surface-modified biphasic calcium phosphate (mBCP)/poly-L-Lactide (PLLA) biocomposite was investigated through a series of experiments in vitro and in vivo. Acute toxicity and short term systemic toxicity experiments revealed no toxicity of the materials. Hemolysis assay indicated the good blood compatibility of the composite. In cytotoxicity assay, L929 mouse fibroblasts could well differentiate and proliferate. Animal experiments in vivo were.performed by implanting the materials into rabbits muscle for 8 weeks. The decreasing of inflammatory cells, the building of fibrous tissue layer as well as the growing of blood cells into materials indicated the nontoxicity of the composite. Based on the experiment results, surfacemodified BCP/PLLA biocomposite is proven to have superior biocompatibility, which would be a promising bone repairing material.
基金supported by the National Key Research and Development Program of China from Ministry of Science and Technology(2016YFC1100502)Key Research Program of Frontier Sciences(QYZDJ-SSW-JSC031)from Chinese Academy of Sciences(CAS)+1 种基金Key Research and Development Program of Liaoning Province(2017105005)Shenyang Key R&D and Technology Transfer Program(Z17-7-023)。
文摘Magnesium(Mg^2+))ion plays important roles in biomineralization of bone,teeth and calcium carbonate skeletons.Herein,chicken eggshells mainly comprising of Mg-calcite nanocrystals(Mg/(Mg+Ca)2.0 mol.%)were used to fabricate biphasic calcium phosphate(BCP),a mixture of hydroxyapatite(HA)and p-tricalcium phosphate(p-TCP)nanocrystals,through hydrothermal reactions at 200℃for 24 h.Our results indicated thatβ-TCP nanocrystals formed through the ion-exchange reactions of Mg-calcite,while HA nanocrystals were mainly produced by dissolution-reprecipitation reactions on the surfaces of eggshell samples in the hydrothermal system.Mg substitution in calcite resulted in formation ofβ-TCP nanocrystals instead of HA crystals through ion-exchange reactions.BCP samples with different compositions(28.6-77.8 wt.%β-TCP)were produced by controlling particle sizes of eggshells for hydrothermal reactions.The larger particles lead to the larger proportion ofβ-TCP in the BCP composition.Therefore,Mg substitution and particle size had synergetic effects on the hydrothermal synthesis of BCP using chicken eggshells through balance of ion-exchange and dissolution-reprecipitation reactions.Cell culture results showed that the BCP products were non-cytotoxic to MC3 T3-E1 cells,which may be used for bone substitute materials in future.
基金This study was financially supported by the National Natural Science Foundation of China(No.81571021).
文摘The combination between biphasic calcium phosphate(BCP)and the osteomimetic porous microstructure obtained via freeze casting is hoped to achieve excellent bone regeneration,while the effects of HA and b-TCP ratio changes on the degradation and biological performance of the BCP scaffolds with this unique microstructure need to be determined.Here,we prepared the osteomimetic BCP scaffolds with different HA/b-TCP ratios(HA30/b-TCP70,HA50/b-TCP50,HA70/b-TCP30)and the effects of different HA/b-TCPHA/b-TCP ratios on the degradation and biological performance were studied in vitro and vivo.These BCP scaffolds with different HA/b-TCP ratios exhibited similar microstructure,mechanical performance,and protein absorption capability,while HA70/b-TCP30 BCP scaffolds showed an advisable degradation rate.Study in vitro confirmed the bio-compatibility and promotion on the proliferation,differentiation of MG63 cells in the porous osteomimetic BCP scaffolds with a HA/b-TCP ratio at 30:70.Implantation experiments also showed that the porous osteomimetic BCP scaffolds with a HA/b-TCP ratio at 30:70 had excellent bone regeneration capacity and proper degradation rate compatible with bone growth.These results reveal that the porous osteomimetic BCP scaffold with a HA/b-TCP ratio at 30:70 is a potential candidate of biodegradable bone substitutes used for bone repair.
基金This work was supported by grants from the National Natural Science Foundation of China (No.81271954,No.81102604),Shanghai Science and Technology Program (No.12QH1402700),and the National Basic Research Program of China (No.2009CB930000).
文摘Background Bone grafting is commonly used to repair bone defects.As the porosity of the graft scaffold increases,bone formation increases,but the strength decreases.Early attempts to engineer materials were not able to resolve this problem.In recent years,nanomaterials have demonstrated the unique ability to improve the material strength and toughness while stimulating new bone formation.In our previous studies,we synthesized a nano-scale material by reinforcing a porous β-tricalcium phosphate (β-TCP) ceramic scaffold with Na2O-MgO-P2O5-CaO bioglass (β-TCP/BG).However,the in vivo effects of the β-TCP/BG scaffold on bone repair remain unknown.Methods We investigated the efficacy of β-TCP/BG scaffolds compared to autografts in a canine tibioflbula defect model.The tibioflbula defects were created in the right legs of 12 dogs,which were randomly assigned to either the scaffold group or the autograft group (six dogs per group).Radiographic evaluation was performed at 0,4,8,and 12 weeks post-surgery.The involved tibias were extracted at 12 weeks and were tested to failure via a three-point bending.After the biomechanical analysis,specimens were subsequently processed for scanning electron microscopy analysis and histological evaluations.Results Radiographic evaluation at 12 weeks post-operation revealed many newly formed osseous calluses and bony unions in both groups.Both the maximum force and break force in the scaffold group (n=6) were comparable to those in the autograft group (n=6,P >0.05),suggesting that the tissue-engineered bone repair achieved similar biomechanical properties to autograft bone repair.At 12 weeks post-operation,obvious new bone and blood vessel formations were observed in the artificial bone of the experimental group.Conclusions The results demonstrated that new bone formation and high bone strength were achieved in the β-TCP/ BG scaffold group,and suggested that the β-TCP/BG scaffold could be used as a synthetic alternative to autografts for the repair of bone defects.
基金sponsored by the National Key Research and Development Program of China(No.2017YFB0702602)the National Nature Science Foundation of China(Nos.31971283 and 31670985)Sichuan Science and Technology Innovation Team of China(No.2019JDTD0008).
文摘Immune systems play a critical role in the regulation of bone formation and homeostasis,which arouses a growing interest in the development of biomaterials that can modulate both immune response and osteogenesis.In this study,biphasic calcium phosphate(BCP)ceramics were modified with different whiskered surface,and their effects on macrophage polarization and functional status were investigated.The results showed that compared to BCP-W ceramics with long and solid whiskers,BCPHW ceramics with short and hollow whiskers surface were conducive to protein adsorption and macrophage elongation.Furthermore,BCP-HW ceramics down-regulated the expression of M1 macrophage markers(Il1β,Tnfα,and iNos),promoted the expression of M2 macrophage markers(Il10 and Arg)and growth factors(Tgfβ1 and Bmp2),which might be attributed to the differential integrin expression regulated by different whisker structures.The conditioned medium derived from the supernatant of macrophage/whiskered ceramic co-culture was further used to culture MC3T3-E1 pre-osteoblasts to evaluate the effects of whiskered ceramic-mediated macrophage secretion on osteogenesis in vitro.Compared with BCP-W ones,the secretion pattern induced by BCP-HW ceramics could promote the expression of bone markers in pre-osteoblasts,which might due to the activation of intracellular signaling cascades like BMP/Smad and TGF-β/Smad signaling pathways.A murine intramuscular implantation model suggested that after implantation for 1,2,and 3 weeks,BCP-HW ceramics drove the switch of macrophages to ARG+wound-healing M2 phenotype,while BCP-W ceramics increased the proportion of iNOS+M1 inflammatory macrophages.At 2 months,only BCP-HW could induce ectopic bone formation.Taken together,these results indicated that BCP ceramics with hollow whiskers were capable of creating a proper inflammatory microenvironment to induce bone formation.These whiskered BCP ceramics with good osteo-immunomodulatory capacity hold promise in serving as bone grafts to achieve desired bone repair and regeneration.
基金the National Key Research and Development Program of China(Grant No.2022YFC2401801)National Science Foundation of China(Grant No.52002256)+1 种基金Major Project of Sichuan Science and Technology Department(Grant Nos.2022ZDZX0029 and 2021YFS0032)Sichuan University“Zero to one”Innovation Research Project(Grant No.2022SCUH0044).
文摘How to endow bone grafts with long-term antibacterial activity and good bone regenerative ability to achieve the regenerative repair of infected bone defects has been the focus of the clinical treatment of osteomyelitis.The present study introduced a novel one-step route to realizing the co-doping of zinc oxide(ZnO)and zinc ion(Zn^(2+))in biphasic calcium phosphate(BCP)ceramics to utilize their synergistic antibacterial.Compared with the conventional BCP ceramics(BCP-Ca),the ZnO/Zn^(2+)co-doping ones(BCP-Zn)possessed strong antibacterial ability on E.coli and S.aureus as well as stimulated the osteogenic differentiation of bone marrow mesenchymal stem cells(BMSCs)effectively.The synergistic antibacterial mechanism of ZnO and Zn^(2+)was also investigated.BCP-Zn showed excellent osteoinductivity and angiogenesis at three months postoperatively in the canine intramuscular implantation model.Moreover,BCP-Zn exhibited excellent anti-infective ability and bone regenerative repair compared to BCP-Ca and control groups in the infected bone defect model of rat femur.Collectively,these findings suggest that the simultaneous introduction of ZnO/Zn^(2+)could have immense potential to expand the application of osteoinductive BCP ceramics in the regenerative repair of infected bone defects.