背景:骨及血管组织的天然压电性能,吸引了大量关于压电材料在血管化骨组织再生领域的研究。因此,深入研究压电材料在骨及血管电学微环境下对细胞行为及组织再生的影响,有利于突破组织工程骨移植物新生血管化不足这一限制,实现其在临床...背景:骨及血管组织的天然压电性能,吸引了大量关于压电材料在血管化骨组织再生领域的研究。因此,深入研究压电材料在骨及血管电学微环境下对细胞行为及组织再生的影响,有利于突破组织工程骨移植物新生血管化不足这一限制,实现其在临床中的广泛应用。目的:综述压电生物材料在血管化骨再生研究领域中的应用及进展。方法:以“压电材料,骨再生,血管化,血管生成”为中文检索词,以“piezoelectric material,bone regeneration,vascularization,angiogenesis”为英文检索词,在PubMed、Web of Science、中国知网数据库中检索发表于2011-2021年的相关研究论著。结果与结论:压电生物材料具备良好的压电性能和生物相容性,可以通过压电作用产生电信号,刺激骨组织和血管组织,对组织再生进行调控,弥补惰性生物材料活性不足的缺陷,在血管化骨再生领域具有良好的应用前景。然而,目前调控压电材料促进组织修复的机制尚不明确,以血管化骨再生整体为目标的综合研究数量较少,压电材料性能方面也存在诸如不可生物降解及机械性能不足等缺点,亟待解决。展开更多
The bone regenerative scaffold with the tailored degradation rate matching with the growth rate of the new bone is essential for adolescent bone repair.To satisfy these requirement,we proposed bone tissue scaffolds wi...The bone regenerative scaffold with the tailored degradation rate matching with the growth rate of the new bone is essential for adolescent bone repair.To satisfy these requirement,we proposed bone tissue scaffolds with controlled degradation rate using osteoinductive materials(Ca-P bioceramics),which is expected to present a controllable biodegradation rate for patients who need bone regeneration.Physicochemical properties,porosity,compressive strength and degradation properties of the scaffolds were studied.3D printed Ca-P scaffold(3DS),gas foaming Ca-P scaffold(FS)and autogenous bone(AB)were used in vivo for personalized beagle skull defect repair.Histological results indicated that the 3DS was highly vascularized and well combined with surrounding tissues.FS showed obvious newly formed bone tissues.AB showed the best repair effect,but it was found that AB scaffolds were partially absorbed and degraded.This study indicated that the 3D printed Ca-P bioceramics with tailored biodegradation rate is a promising candidate for personalized skull bone tissue reconstruction.展开更多
Calcium phosphate bio-ceramics are osteo-conductive,but it remains a challenge to promote the induction of bone augmentation and capillary formation.The surface micro/nano-topography of materials can be recognized by ...Calcium phosphate bio-ceramics are osteo-conductive,but it remains a challenge to promote the induction of bone augmentation and capillary formation.The surface micro/nano-topography of materials can be recognized by cells and then the cell fate are mediated.Traditional regulation methods of carving surface structures on bio-ceramics employ mineral reagents and organic additives,which might introduce impurity phases and affect the biological results.In a previous study,a facile and novel method was utilized with ultrapure water as the unique reagent for hydrothermal treatment,and a uniform hydroxyapatite(HAp)surface layer was constructed on composite ceramics(β-TCP/CaSiO_(3))in situ.Further combined with 3D printing technology,biomimetic hierarchical structure scaffolds were fabricated with interconnected porous composite ceramic scaffolds as the architecture and micro/nano-rod hybrid HAp as the surface layer.The obtained HAp surface layer favoured cell adhesion,alleviated the cytotoxicity of precursor scaffolds,and upregulated the cellular differentiation of mBMSCs and gene expression of HUVECs in vitro.In vivo studies showed that capillary formation,bone augmentation and new bone matrix formation were upregulated after the HAp surface layer was obtained,and the results confirmed that the fabricated biomimetic hierarchical structure scaffold could be an effective candidate for bone regeneration.展开更多
In order to study the influence of rubidium(Rb)addition on the phase composition,microstructure,mechanical properties and cell response of bioactive glass-ceramics,CaO−SiO2−Na2O−B2O3−MgO−ZnO−P2O5 glass system was desi...In order to study the influence of rubidium(Rb)addition on the phase composition,microstructure,mechanical properties and cell response of bioactive glass-ceramics,CaO−SiO2−Na2O−B2O3−MgO−ZnO−P2O5 glass system was designed with and without addition of Rb.The results show that hydroxyapatite(HA)and Mg−whitelockite(Ca18Mg2H2(PO4)14)crystalline phases are formed in the glass matrix without Rb.After the addition of Rb,only HA phase is detected.The grain size of the crystals in the glass-ceramics is larger with the addition of Rb than that of samples without Rb.Rb addition can improve the bending strength of glass-ceramics.The cultivation of human bone marrow mesenchymal stem cells(hBMSCs)on Rb-containing glass-ceramics demonstrates enhanced cell adhesion,proliferation and ALP activity.In conclusion,Rb-modified glass-ceramics exhibit good mechanical property,excellent bioactivity and biocompatibility,which have potential for bone regeneration application.展开更多
The architecture and surface modifications have been regarded as effective methods to enhance the bi-ological response of biomaterials in bone tissue engineering.The porous architecture of the implanta-tion was essent...The architecture and surface modifications have been regarded as effective methods to enhance the bi-ological response of biomaterials in bone tissue engineering.The porous architecture of the implanta-tion was essential conditions for bone regeneration.Meanwhile,the design of biomimetic hydroxyap-atite(HAp)coating on porous scaffolds was demonstrated to strengthen the bioactivity and stimulate osteogenesis.However,bioactive bio-ceramics such asβ-tricalcium phosphate(β-TCP)and calcium sili-cate(CS)with superior apatite-forming ability were reported to present better osteogenic activity than that of HAp.Hence in this study,3D-printed interconnected porous bioactive ceramicsβ-TCP/CS scaf-fold was fabricated and the biomimetic HAp apatite coating were constructed in situ via hydrothermal reaction,and the effects of HAp apatite layer on the fate of mouse bone mesenchymal stem cells(mBM-SCs)and the potential mechanisms were explored.The results indicated that HAp apatite coating en-hanced cell proliferation,alkaline phosphatase(ALP)activity,and osteogenic gene expression.Further-more,PI3K/AKT/mTOR signaling pathway is proved to have an important impact on cellular functions.The present results demonstrated that the key molecules of phosphatidylinositol 3-kinase(PI3K),protein kinase B(AKT)and mammalian target of rapamycin(mTOR)were activated after the biomimetic hydrox-yapatite coating were constructed on the 3D-printed ceramic scaffolds.Besides,the activated influence on the protein expression of Runx2 and BMP2 could be suppressed after the treatment of inhibitor HY-10358.In vivo studies showed that the constructed HAp coating promoted bone formation and strengthen the bone quality.These results suggest that biomimetic HAp coating constructed on the 3D-printed bioac-tive composite scaffolds could strengthen the bioactivity and the obtained biomimetic multi-structured scaffolds might be a potential alternative bone graft for bone regeneration.展开更多
Critical bone defects caused by extensive excision of malignant bone tumor and the probability of tumor recurrence due to residual tumor cells make malignant bone tumor treatment a major clinical challenge.The present...Critical bone defects caused by extensive excision of malignant bone tumor and the probability of tumor recurrence due to residual tumor cells make malignant bone tumor treatment a major clinical challenge.The present therapeutic strategy concentrates on implanting bone substitutes for defect filling but suffers from failures in both enhancing bone regeneration and inhibiting the growth of tumor cells.Herein,Cu and Mn-doped borosilicate nanoparticles(BSNs)were developed for syncretic bone repairing and anti-tumor treatment,which can enhance bone regeneration through the osteogenic effects of Cu^(2+) and Mn^(3+) ions and meanwhile induce tumor cells apoptosis through the hydroxyl radicals produced by the Fenton-like reactions of Cu^(2+) and Mn^(3+) ions.In vitro study showed that both osteogenic differentiation of BMSCs and angiogenesis of endothelial cells were promoted by BSNs,and consistently the critical bone defects of rats were efficiently repaired by BSNs through in vivo evaluation.Meanwhile,BSNs could generate hydroxyl radicals through Fenton-like reactions in the simulated tumor microenvironment,promote the generation of intracellular reactive oxygen species,and eventually induce tumor cell apoptosis.Besides,subcutaneous tumors of mice were effectively inhibited by BSNs without causing toxic side effects to normal tissues and organs.Altogether,Cu and Mn-doped BSNs developed in this work performed dual functions of enhancing osteogenesis and angiogenesis for bone regeneration,and inhibiting tumor growth for chemodynamic therapy,thus holding a great potential for syncretic bone repairing and anti-tumor therapy.展开更多
In this paper,we used Corn Stalk(CS)as a renewable and economical bio template to fabricate willemite scaffolds with the potential application in skull bone repair.CS was used as a sacrificial template to synthesize t...In this paper,we used Corn Stalk(CS)as a renewable and economical bio template to fabricate willemite scaffolds with the potential application in skull bone repair.CS was used as a sacrificial template to synthesize the scaffolds.Willemite scaffolds with the chemical formula of Zn2SiO4 and pore size in the range of 3 to 10µm could be successfully synthesized by soaking CS in the willemite solution for 24 h and sintering at 950°C for 5 h.The porosity of the samples was controlled by the soaking time(between 12 and 48 h)in the willemite solution from 5 to 35%,respectively.The properties of these scaffolds showed a good approximation with cranial bone tissue.In addition,cytotoxicity assays(MTT)were performed on Human Bone Marrow Stromal cells(HBMSc)and A172 human glioblastoma cell lines by direct and indirect culture methods to estimate their toxicity for bone and nerve cells,respectively.Alkaline Phosphatase(ALP)activity and DAPI/Phalloidin cell staining were also performed to investigate the efficiency of the scaffolds for bone tissue engineering applications.The results showed that the scaffolds had good biocompatibility with both HBMSC and A172 cells,noticeable improvement on ALP activity,and great apatite formation ability in Simulated Body Fluid(SBF).All the evidence ascertained that willemite scaffolds made by corn stalks could be a useful candidate for bone tissue engineering applications.展开更多
The magnetic porous tricalcium phosphate (MPTCP) and porous tricalcium phosphate (PTCP) ceramic cylinders were implanted into right and left bone defects of rabbits' radii in order to determine the utility of the ...The magnetic porous tricalcium phosphate (MPTCP) and porous tricalcium phosphate (PTCP) ceramic cylinders were implanted into right and left bone defects of rabbits' radii in order to determine the utility of the MPTCP ceramics. Based on naked eye inspection, light and scanning electron microphotography, roentgenography,quantitative histological measurement of new bone formation and anti-break test for a period of 5 months. The results showed that the two kinds of ceramics were biocompatible with human tissue. MPTCP ceramics could induce more new bone formation than PTCP ceramics. Treatment of fractures with synthetic calcium phosphate ceramics and magnetic fields were discussed.展开更多
文摘背景:骨及血管组织的天然压电性能,吸引了大量关于压电材料在血管化骨组织再生领域的研究。因此,深入研究压电材料在骨及血管电学微环境下对细胞行为及组织再生的影响,有利于突破组织工程骨移植物新生血管化不足这一限制,实现其在临床中的广泛应用。目的:综述压电生物材料在血管化骨再生研究领域中的应用及进展。方法:以“压电材料,骨再生,血管化,血管生成”为中文检索词,以“piezoelectric material,bone regeneration,vascularization,angiogenesis”为英文检索词,在PubMed、Web of Science、中国知网数据库中检索发表于2011-2021年的相关研究论著。结果与结论:压电生物材料具备良好的压电性能和生物相容性,可以通过压电作用产生电信号,刺激骨组织和血管组织,对组织再生进行调控,弥补惰性生物材料活性不足的缺陷,在血管化骨再生领域具有良好的应用前景。然而,目前调控压电材料促进组织修复的机制尚不明确,以血管化骨再生整体为目标的综合研究数量较少,压电材料性能方面也存在诸如不可生物降解及机械性能不足等缺点,亟待解决。
基金This work was supported by the National Key Research and Development Program of China(No.18YFB1105600,2018YFC1106800)National Natural Science Foundation of China(51875518)+1 种基金Sichuan Province Science&Technology Department Projects(2016CZYD0004,2017SZ0001,2018GZ0142,2019YFH0079)Research Foundation for Young Teachers of Sichuan University(2018SCUH0017)and The“111”Project(No.B16033).
文摘The bone regenerative scaffold with the tailored degradation rate matching with the growth rate of the new bone is essential for adolescent bone repair.To satisfy these requirement,we proposed bone tissue scaffolds with controlled degradation rate using osteoinductive materials(Ca-P bioceramics),which is expected to present a controllable biodegradation rate for patients who need bone regeneration.Physicochemical properties,porosity,compressive strength and degradation properties of the scaffolds were studied.3D printed Ca-P scaffold(3DS),gas foaming Ca-P scaffold(FS)and autogenous bone(AB)were used in vivo for personalized beagle skull defect repair.Histological results indicated that the 3DS was highly vascularized and well combined with surrounding tissues.FS showed obvious newly formed bone tissues.AB showed the best repair effect,but it was found that AB scaffolds were partially absorbed and degraded.This study indicated that the 3D printed Ca-P bioceramics with tailored biodegradation rate is a promising candidate for personalized skull bone tissue reconstruction.
基金financially supported by the National key research and development plan(Grant No.2017YFC1105000,Grant No.2017YFA0205600)Outstanding Scholar Program of Guangzhou Regenerative Medicine and Health Guangdong Laboratory(2018GZR110102001)+4 种基金the Science and Technology Program of Guangdong Province(Grant No.2019B010941002)the Science and Technology Program of Guangzhou(Grant No.201804020060,Grant No.202007020002)Natural Science Foundation of Guangdong Province(Grant No.2021A1515011741,2020A1515011354)the National Nature Science Foundation of China(Grants U1801252),National Natural Science Foundation of China(31700823)Guangzhou Science and Technology Planning Project(202102020005).
文摘Calcium phosphate bio-ceramics are osteo-conductive,but it remains a challenge to promote the induction of bone augmentation and capillary formation.The surface micro/nano-topography of materials can be recognized by cells and then the cell fate are mediated.Traditional regulation methods of carving surface structures on bio-ceramics employ mineral reagents and organic additives,which might introduce impurity phases and affect the biological results.In a previous study,a facile and novel method was utilized with ultrapure water as the unique reagent for hydrothermal treatment,and a uniform hydroxyapatite(HAp)surface layer was constructed on composite ceramics(β-TCP/CaSiO_(3))in situ.Further combined with 3D printing technology,biomimetic hierarchical structure scaffolds were fabricated with interconnected porous composite ceramic scaffolds as the architecture and micro/nano-rod hybrid HAp as the surface layer.The obtained HAp surface layer favoured cell adhesion,alleviated the cytotoxicity of precursor scaffolds,and upregulated the cellular differentiation of mBMSCs and gene expression of HUVECs in vitro.In vivo studies showed that capillary formation,bone augmentation and new bone matrix formation were upregulated after the HAp surface layer was obtained,and the results confirmed that the fabricated biomimetic hierarchical structure scaffold could be an effective candidate for bone regeneration.
基金The authors are grateful for the financial supports from the Natural Science Foundation of Hunan Province,China(2019JJ50797)the Postdoctoral Science Foundation of China(2019T120711).
文摘In order to study the influence of rubidium(Rb)addition on the phase composition,microstructure,mechanical properties and cell response of bioactive glass-ceramics,CaO−SiO2−Na2O−B2O3−MgO−ZnO−P2O5 glass system was designed with and without addition of Rb.The results show that hydroxyapatite(HA)and Mg−whitelockite(Ca18Mg2H2(PO4)14)crystalline phases are formed in the glass matrix without Rb.After the addition of Rb,only HA phase is detected.The grain size of the crystals in the glass-ceramics is larger with the addition of Rb than that of samples without Rb.Rb addition can improve the bending strength of glass-ceramics.The cultivation of human bone marrow mesenchymal stem cells(hBMSCs)on Rb-containing glass-ceramics demonstrates enhanced cell adhesion,proliferation and ALP activity.In conclusion,Rb-modified glass-ceramics exhibit good mechanical property,excellent bioactivity and biocompatibility,which have potential for bone regeneration application.
基金This work was sponsored by the National Science Foundation of China(Nos.32071341,52202358,52003302)The Natural Science Foundation of Guangdong Province(No.2017A030308004)+1 种基金the Guangdong Basic and Applied Basic Research Foundation(No.2021A1515110824)the Science and Technology Project of Guangdong province(No.2018A050506021).
文摘The architecture and surface modifications have been regarded as effective methods to enhance the bi-ological response of biomaterials in bone tissue engineering.The porous architecture of the implanta-tion was essential conditions for bone regeneration.Meanwhile,the design of biomimetic hydroxyap-atite(HAp)coating on porous scaffolds was demonstrated to strengthen the bioactivity and stimulate osteogenesis.However,bioactive bio-ceramics such asβ-tricalcium phosphate(β-TCP)and calcium sili-cate(CS)with superior apatite-forming ability were reported to present better osteogenic activity than that of HAp.Hence in this study,3D-printed interconnected porous bioactive ceramicsβ-TCP/CS scaf-fold was fabricated and the biomimetic HAp apatite coating were constructed in situ via hydrothermal reaction,and the effects of HAp apatite layer on the fate of mouse bone mesenchymal stem cells(mBM-SCs)and the potential mechanisms were explored.The results indicated that HAp apatite coating en-hanced cell proliferation,alkaline phosphatase(ALP)activity,and osteogenic gene expression.Further-more,PI3K/AKT/mTOR signaling pathway is proved to have an important impact on cellular functions.The present results demonstrated that the key molecules of phosphatidylinositol 3-kinase(PI3K),protein kinase B(AKT)and mammalian target of rapamycin(mTOR)were activated after the biomimetic hydrox-yapatite coating were constructed on the 3D-printed ceramic scaffolds.Besides,the activated influence on the protein expression of Runx2 and BMP2 could be suppressed after the treatment of inhibitor HY-10358.In vivo studies showed that the constructed HAp coating promoted bone formation and strengthen the bone quality.These results suggest that biomimetic HAp coating constructed on the 3D-printed bioac-tive composite scaffolds could strengthen the bioactivity and the obtained biomimetic multi-structured scaffolds might be a potential alternative bone graft for bone regeneration.
基金funded by National Key Research and Development Program of China(Grant No.2018YFC1106302 and 2018YFA0703100)National Natural Science Foundation of China(Grant No.51772210,U2001221,51802340,81871774 and 82072422)+1 种基金Frontier Science Key Research Programs of CAS(Grant No.QYZDB-SSW-JSC030)Shenzhen Fundamental Research Foundation(Grant No.JCYJ20200109114620793).
文摘Critical bone defects caused by extensive excision of malignant bone tumor and the probability of tumor recurrence due to residual tumor cells make malignant bone tumor treatment a major clinical challenge.The present therapeutic strategy concentrates on implanting bone substitutes for defect filling but suffers from failures in both enhancing bone regeneration and inhibiting the growth of tumor cells.Herein,Cu and Mn-doped borosilicate nanoparticles(BSNs)were developed for syncretic bone repairing and anti-tumor treatment,which can enhance bone regeneration through the osteogenic effects of Cu^(2+) and Mn^(3+) ions and meanwhile induce tumor cells apoptosis through the hydroxyl radicals produced by the Fenton-like reactions of Cu^(2+) and Mn^(3+) ions.In vitro study showed that both osteogenic differentiation of BMSCs and angiogenesis of endothelial cells were promoted by BSNs,and consistently the critical bone defects of rats were efficiently repaired by BSNs through in vivo evaluation.Meanwhile,BSNs could generate hydroxyl radicals through Fenton-like reactions in the simulated tumor microenvironment,promote the generation of intracellular reactive oxygen species,and eventually induce tumor cell apoptosis.Besides,subcutaneous tumors of mice were effectively inhibited by BSNs without causing toxic side effects to normal tissues and organs.Altogether,Cu and Mn-doped BSNs developed in this work performed dual functions of enhancing osteogenesis and angiogenesis for bone regeneration,and inhibiting tumor growth for chemodynamic therapy,thus holding a great potential for syncretic bone repairing and anti-tumor therapy.
文摘In this paper,we used Corn Stalk(CS)as a renewable and economical bio template to fabricate willemite scaffolds with the potential application in skull bone repair.CS was used as a sacrificial template to synthesize the scaffolds.Willemite scaffolds with the chemical formula of Zn2SiO4 and pore size in the range of 3 to 10µm could be successfully synthesized by soaking CS in the willemite solution for 24 h and sintering at 950°C for 5 h.The porosity of the samples was controlled by the soaking time(between 12 and 48 h)in the willemite solution from 5 to 35%,respectively.The properties of these scaffolds showed a good approximation with cranial bone tissue.In addition,cytotoxicity assays(MTT)were performed on Human Bone Marrow Stromal cells(HBMSc)and A172 human glioblastoma cell lines by direct and indirect culture methods to estimate their toxicity for bone and nerve cells,respectively.Alkaline Phosphatase(ALP)activity and DAPI/Phalloidin cell staining were also performed to investigate the efficiency of the scaffolds for bone tissue engineering applications.The results showed that the scaffolds had good biocompatibility with both HBMSC and A172 cells,noticeable improvement on ALP activity,and great apatite formation ability in Simulated Body Fluid(SBF).All the evidence ascertained that willemite scaffolds made by corn stalks could be a useful candidate for bone tissue engineering applications.
文摘The magnetic porous tricalcium phosphate (MPTCP) and porous tricalcium phosphate (PTCP) ceramic cylinders were implanted into right and left bone defects of rabbits' radii in order to determine the utility of the MPTCP ceramics. Based on naked eye inspection, light and scanning electron microphotography, roentgenography,quantitative histological measurement of new bone formation and anti-break test for a period of 5 months. The results showed that the two kinds of ceramics were biocompatible with human tissue. MPTCP ceramics could induce more new bone formation than PTCP ceramics. Treatment of fractures with synthetic calcium phosphate ceramics and magnetic fields were discussed.
