CNTs及其复合材料在医用材料领域的应用
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摘要
碳纳米管(CNTs)具有良好的强度和韧性,较大的长径比和比表面积,以及独特的力学、电学、磁学和光学特性,并且表现出良好的生物相容性与生物功能性。基于CNTs独特的结构,研究人员可通过对其修饰和改性,制备出性能优良的CNTs及其复合材料,从而广泛应用于医用材料领域。综述了CNTs及其复合材料在神经/骨组织工程、血管修复与再生、药物/基因载体中的应用,讨论了其在医用材料领域中的生物安全性问题,并对目前亟待研究的重要问题及研究方向进行了展望。
Carbon nanotubes(CNTs)exhibit excellent strength and toughness,large aspect ratio and specific surface area,and special mechanical,electrical,magnetic and optical properties.Meanwhile,CNTs show preferable biocompatibility and biofunction.What's more,CNTs can be easily modified by researchers because of their unique structure.Therefore,excellent CNTs based composites were widely used in the field of biomedical materials.In this present review,the applications of CNTs and CNTs based composites in the field of nerve tissue engineering,bone tissue engineering,vascular repair and angiogenesis,and drug or gene carriers were discussed.Moreover,the biosecurity is one of the crucial issues in the field of biomedical materials.It has attracted more attention for the researchers.The progressive directions of the important issues are also discussed and expected.
Carbon nanotubes(CNTs)exhibit excellent strength and toughness,large aspect ratio and specific surface area,and special mechanical,electrical,magnetic and optical properties.Meanwhile,CNTs show preferable biocompatibility and biofunction.What's more,CNTs can be easily modified by researchers because of their unique structure.Therefore,excellent CNTs based composites were widely used in the field of biomedical materials.In this present review,the applications of CNTs and CNTs based composites in the field of nerve tissue engineering,bone tissue engineering,vascular repair and angiogenesis,and drug or gene carriers were discussed.Moreover,the biosecurity is one of the crucial issues in the field of biomedical materials.It has attracted more attention for the researchers.The progressive directions of the important issues are also discussed and expected.
引文
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[13] Wu S,Duan B,Lu A,et al.Biocompatible chitin/carbon nanotubes composite hydrogels as neuronal growth substrates[J].Carbohydrate Polymers,2017,174:830-840.
[14] Wu Tao.Preparation of nanocarbon-based magnetic composite and its application in calcium phosphate cement[D].Chengdu:Southwest Jiaotong University,2017.吴涛.纳米碳基磁性复合材料的制备及在磷酸钙骨水泥中的应用[D].成都:西南交通大学,2017.
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[16] Xiao Zhenkun,Wu Lei,Mi Rao,et al.Effect of carbon nanotubes on the mechanical properties of carbon nanotubes/hydroxyapatite composites[J].Chinese Journal of Inorganic Chemistry,2015,31(1):114-120(in Chinese).肖镇昆,吴磊,米饶,等.碳纳米管对羟基磷灰石基复合材料力学性能的影响[J].无机化学学报,2015,31(1):114-120.
[17] Zhang R, Metoki N, Sharabani-Yosef O, et al.Hydroxyapatite/mesoporous graphene/single-walled carbon nanotubes freestanding flexible hybrid membranes for regenerative medicine[J].Advanced Functional Materials,2016,26(44):7965-7974.
[18] King Alice A K,Matta-Domjan B,Large M J,et al.Pristine carbon nanotube scaffolds for the growth of chondrocytes[J].Journal of Materials Chemistry B,2017,5(41):8178-8182.
[19] Shrestha B K,Shrestha S,Tiwari A P,et al.Bio-inspired hybrid scaffold of zinc oxide-functionalized multiwall carbon nanotubes reinforced polyurethane nanofibers for bone tissue engineering[J].Materials&Design,2017,133:69-81.
[20] Zhu S,Jing W,Hu X,et al.Time-dependent effect of electrical stimulation on osteogenic differentiation of bone mesenchymal stromal cells cultured on conductive nanofibers[J].Journal of Biomedical Materials Research Part A,2017,105(12):3369-3383.
[21] Xu Yong,Wang Jing,Hu Jinping,et al.Purification of multi-walled carbon nanotubes and its surface modification[J].Sciencepaper Online,2010,5(6):423-426(in Chinese).许永,王静,胡金平,等.多壁碳纳米管的纯化及表面修饰[J].中国科技论文,2010,5(6):423-426.
[22] Leo N D,Battaglini M,Berger L,et al.A catechin nanoformulation inhibits WM266melanoma cell proliferation,migration and associated neo-angiogenesis[J].European Journal of Pharmaceutics and Biopharmaceutics,2017,114:1-10.
[23] Feng Xueyi,Liu Zhengni,Tang Rui,et al.Constructing a vascular endothelial growth factor sustained-released multi-wall carbon nanotube composite scaffold[J].Journal of Clinical Rehabilitative Tissue Engineering Research,2013,17(3):433-439(in Chinese).冯学艺,刘正尼,汤睿,等.构建可控释血管内皮生长因子多壁碳纳米管的复合支架[J].中国组织工程研究,2013,17(3):433-439.
[24] Zhao Guangyu.Experimental studies on the construction and neovascularation of carbon nano-tube/α-tricalcium phosphate(CNT/TCP)as tissue engineeing bone[D].Ji’nan:Shandong University,2006.赵光宇.碳纳米管复合磷酸钙骨水泥(CNT/TCP)修复兔颅骨缺损及其血管再生的实验研究[D].济南:山东大学,2006.
[25] Long J,Xiao Y,Liu L,et al.The adverse vascular effects of multi-walled carbon nanotubes(MWCNTs)to human vein endothelial cells(HUVECs)in vitro:role of length of MWCNTs[J].Journal of Nanobiotechnology,2017,15:1-13.
[26] Lin Zhiqing,Wang Yu,Xi Zhuge,et al.Rat aortic endothelium damage caused by carbon nanotubes exposure[J].Journal of Environment and Health,2008,25(12):1042-1046(in Chinese).林治卿,王玉,袭著革,等.碳纳米管暴露致大鼠主动脉血管内皮损伤作用的研究[J].环境与健康杂志,2008,25(12):1042-1046.
[27] Vashist S K,Zheng D,Pastorin G,et al.Delivery of drugs and biomolecules using carbon nanotubes[J].Carbon,2011,49(13):4077-4097.
[28] Bao Qun.Application in the field of carbon nanotubes in drug carrier[J].Journal of Juamjusi Education Institute,2014(9):322-323(in Chinese).鲍群.碳纳米管在药物载体领域的应用[J].佳木斯职业学院学报,2014,(9):322-323.
[29] Boncel S,Zajac P,Koziol K K.Liberation of drugs from multi-wall carbon nanotube carriers[J].Journal of Controlled Release,2013,169(1-2):126-140.
[30] Prakash S,Malhotra M,Shao W,et al.Polymeric nanohybrids and functionalized carbon nanotubes as drug delivery carriers for cancer therapy[J].Advanced Drug Delivery Reviews,2011,63(14-15):1340-1351.
[31] Zhong Xinxian,Lin Youcheng,Zeng Jianqiang,et al.Preparation and antineoplastic activity of functionalized carbon nanotubes as drug carriers[J].Journal of Functional Materials,2016,47(6):194-199(in Chinese).钟新仙,林有铖,曾建强,等.药物载体碳纳米管的制备及其抗肿瘤活性[J].功能材料,2016,47(6):194-199.
[32] Tang Youzhi,Liu Yahong.Progress in research of carbon nanotubes as drug carriers[J].Chinese Journal of Veterinary Science,2012,32(10):1587-1591(in Chinese).汤有志,刘雅红.碳纳米管作为药物载体的研究进展[J].中国兽医学报,2012,32(10):1587-1591.
[33] Yu B,Tan L,Zheng R,et al.Targeted delivery and controlled release of paclitaxel for the treatment of lung cancer using single-walled carbon nanotubes[J].Materials Science&Engineering C Materials for Biological Applications,2016,68:579-584.
[34] Gan Li,Yan Xuebin,Zhang Raoxiang,et al.Preparation of functionalized single-walled carbon nanotubes/NR2B-shRNA interference plasmid complex and its application in gene therapy for chronic pain[J].Chinese Journal of Pain Medicine,2013,19(4):220-224(in Chinese).甘丽,阎雪彬,章饶香,等.功能化单壁碳纳米管/NR2B-shRNA干扰质粒复合物的制备及其用于慢性疼痛的基因治疗[J].中国疼痛医学杂志,2013,19(4):220-224.
[35] Gu Xiaoxiao,Du Baoji,Li Yunhui,et al.Vectors based on nanomaterials for gene delivery[J].Progress in Chemistry,2015,27(8):1093-1101(in Chinese).古晓晓,杜宝吉,李云辉,等.基于纳米材料的基因载体[J].化学进展,2015,27(8):1093-1101.
[36] Huang Shuwen.Preparation and characterization of biodegradable polyethylenimine grafted carbon nanotubes as gene vector[D].Wuhan:Wuhan Institute of Technology,2015(in Chinese).黄书文.碳纳米管接枝可降解聚乙烯亚胺基因载体的制备与表征[D].武汉:武汉工程大学,2015.
[37] Wang Yue,Wang Peng,Chen Chunying,et al.Cellular and molecular mechanisms of pulmonary toxicity caused by carbon nanotubes with various physiochemical properties[J].Chinese Science Bulletin,2013,58(21):2007-2020(in Chinese).王越,王鹏,陈春英,等.碳纳米管呼吸系统毒性作用机制及其影响因素的研究进展[J].科学通报,2013,58(21):2007-2020.
[38] Liu Yuanfang,Liu Jiahui,Wang Haifang.Cytotoxicity of pristine carbon nanotubes:mechanism and influencing factors[J].Journal of Shanghai University(Natural Science Edition),2010,16(5):447-459(in Chinese).刘元方,刘佳蕙,王海芳.未修饰碳纳米管的细胞毒性机理及其影响因素[J].上海大学学报(自然科学版),2010,16(5):447-459.
[2] Zhang Jinchao,Yang Kangning,Zhang Haisong,et al.Application status and prospect of carbon-based nanomaterials in biomedical field[J].Progress in Chemistry,2013,25(2):397-408(in Chinese).张金超,杨康宁,张海松,等.碳纳米材料在生物医学领域的应用现状及展望[J].化学进展,2013,25(2):397-408.
[3] Ma Yanhong,Zheng Baozhong,Wei Liangqiang.Review of research on polymer/carbon nanotube composite[J].Plastics,2013,42(5):1-4(in Chinese).马艳红,郑保忠,韦良强.聚合物/碳纳米管复合材料的研究进展[J].塑料,2013,42(5):1-4.
[4] Liu X,Miller A L,Park S,et al.Functionalized carbon nanotube and graphene oxide embedded electric conductive hydrogel synergistically stimulates nerve cell differentiation[J].ACS Appl Mater Interfaces,2017,9(17):14677-14690.
[5] Jiang Aihua,Chen Rui,Bai Ru,et al.Research progress on application of carbon nanotubes and related nanocomposites in nervous systems[J].Acta Biophysica Sinica,2012,28(6):457-468(in Chinese).蒋爱华,陈瑞,白茹,等.碳纳米管及其复合材料在神经系统中的应用研究进展[J].生物物理学报,2012,28(6):457-468.
[6] Hassanzadeh P,Arbabi E,Atyabi F,et al.Nerve growth factor-carbon nanotube complex exerts prolonged protective effects in an in vitro model of ischemic stroke[J].Life Sciences,2017,179:15-22.
[7] Lv Z J,Liu Y,Miao H,et al.Effects of multiwalled carbon nanotubes on electrospun poly(lactide-co-glycolide)-based nanocomposite scaffolds on neural cells proliferation[J].Journal of Biomedical Materials Research Part B Applied Biomaterials,2017,105(5):934-943.
[8] Wang C,Oh S,Lee H A,et al.In vivo feasibility test using transparent carbon nanotube-coated polydimethylsiloxane sheet at brain tissue and sciatic nerve[J].Journal of Biomedical Materials Research Part A,2017,105(6):1736-1745.
[9] Jan E,Kotov N A.Successful differentiation of mouse neural stem cells on layer-by-layer assembled singlewalled carbon nanotube composite[J].Nano Letters,2007,7(5):1123-1128.
[10] Xie J,Chen L,Aatre K R,et al.Somatosensory neurons grown on functionalized carbon nanotube mats[J].Smart Materials&Structures,2006,15(4):85-88.
[11] Lee W,Parpura V.Carbon nanotubes as substrates/scaffolds for neural cell growth[J].Progress in Brain Research,2009,180(8):110-125.
[12] Bareket-Keren L, Hanein Y.Carbon nanotube-based multi electrode arrays for neuronal interfacing:progress and prospects[J].Frontiers in Neural Circuits,2012,6:1-16.
[13] Wu S,Duan B,Lu A,et al.Biocompatible chitin/carbon nanotubes composite hydrogels as neuronal growth substrates[J].Carbohydrate Polymers,2017,174:830-840.
[14] Wu Tao.Preparation of nanocarbon-based magnetic composite and its application in calcium phosphate cement[D].Chengdu:Southwest Jiaotong University,2017.吴涛.纳米碳基磁性复合材料的制备及在磷酸钙骨水泥中的应用[D].成都:西南交通大学,2017.
[15] Gao C,Feng P,Peng S,et al.Carbon nanotube,graphene and boron nitride nanotube reinforced bioactive ceramics for bone repair[J].Acta Biomaterialia,2017,61:1-20.
[16] Xiao Zhenkun,Wu Lei,Mi Rao,et al.Effect of carbon nanotubes on the mechanical properties of carbon nanotubes/hydroxyapatite composites[J].Chinese Journal of Inorganic Chemistry,2015,31(1):114-120(in Chinese).肖镇昆,吴磊,米饶,等.碳纳米管对羟基磷灰石基复合材料力学性能的影响[J].无机化学学报,2015,31(1):114-120.
[17] Zhang R, Metoki N, Sharabani-Yosef O, et al.Hydroxyapatite/mesoporous graphene/single-walled carbon nanotubes freestanding flexible hybrid membranes for regenerative medicine[J].Advanced Functional Materials,2016,26(44):7965-7974.
[18] King Alice A K,Matta-Domjan B,Large M J,et al.Pristine carbon nanotube scaffolds for the growth of chondrocytes[J].Journal of Materials Chemistry B,2017,5(41):8178-8182.
[19] Shrestha B K,Shrestha S,Tiwari A P,et al.Bio-inspired hybrid scaffold of zinc oxide-functionalized multiwall carbon nanotubes reinforced polyurethane nanofibers for bone tissue engineering[J].Materials&Design,2017,133:69-81.
[20] Zhu S,Jing W,Hu X,et al.Time-dependent effect of electrical stimulation on osteogenic differentiation of bone mesenchymal stromal cells cultured on conductive nanofibers[J].Journal of Biomedical Materials Research Part A,2017,105(12):3369-3383.
[21] Xu Yong,Wang Jing,Hu Jinping,et al.Purification of multi-walled carbon nanotubes and its surface modification[J].Sciencepaper Online,2010,5(6):423-426(in Chinese).许永,王静,胡金平,等.多壁碳纳米管的纯化及表面修饰[J].中国科技论文,2010,5(6):423-426.
[22] Leo N D,Battaglini M,Berger L,et al.A catechin nanoformulation inhibits WM266melanoma cell proliferation,migration and associated neo-angiogenesis[J].European Journal of Pharmaceutics and Biopharmaceutics,2017,114:1-10.
[23] Feng Xueyi,Liu Zhengni,Tang Rui,et al.Constructing a vascular endothelial growth factor sustained-released multi-wall carbon nanotube composite scaffold[J].Journal of Clinical Rehabilitative Tissue Engineering Research,2013,17(3):433-439(in Chinese).冯学艺,刘正尼,汤睿,等.构建可控释血管内皮生长因子多壁碳纳米管的复合支架[J].中国组织工程研究,2013,17(3):433-439.
[24] Zhao Guangyu.Experimental studies on the construction and neovascularation of carbon nano-tube/α-tricalcium phosphate(CNT/TCP)as tissue engineeing bone[D].Ji’nan:Shandong University,2006.赵光宇.碳纳米管复合磷酸钙骨水泥(CNT/TCP)修复兔颅骨缺损及其血管再生的实验研究[D].济南:山东大学,2006.
[25] Long J,Xiao Y,Liu L,et al.The adverse vascular effects of multi-walled carbon nanotubes(MWCNTs)to human vein endothelial cells(HUVECs)in vitro:role of length of MWCNTs[J].Journal of Nanobiotechnology,2017,15:1-13.
[26] Lin Zhiqing,Wang Yu,Xi Zhuge,et al.Rat aortic endothelium damage caused by carbon nanotubes exposure[J].Journal of Environment and Health,2008,25(12):1042-1046(in Chinese).林治卿,王玉,袭著革,等.碳纳米管暴露致大鼠主动脉血管内皮损伤作用的研究[J].环境与健康杂志,2008,25(12):1042-1046.
[27] Vashist S K,Zheng D,Pastorin G,et al.Delivery of drugs and biomolecules using carbon nanotubes[J].Carbon,2011,49(13):4077-4097.
[28] Bao Qun.Application in the field of carbon nanotubes in drug carrier[J].Journal of Juamjusi Education Institute,2014(9):322-323(in Chinese).鲍群.碳纳米管在药物载体领域的应用[J].佳木斯职业学院学报,2014,(9):322-323.
[29] Boncel S,Zajac P,Koziol K K.Liberation of drugs from multi-wall carbon nanotube carriers[J].Journal of Controlled Release,2013,169(1-2):126-140.
[30] Prakash S,Malhotra M,Shao W,et al.Polymeric nanohybrids and functionalized carbon nanotubes as drug delivery carriers for cancer therapy[J].Advanced Drug Delivery Reviews,2011,63(14-15):1340-1351.
[31] Zhong Xinxian,Lin Youcheng,Zeng Jianqiang,et al.Preparation and antineoplastic activity of functionalized carbon nanotubes as drug carriers[J].Journal of Functional Materials,2016,47(6):194-199(in Chinese).钟新仙,林有铖,曾建强,等.药物载体碳纳米管的制备及其抗肿瘤活性[J].功能材料,2016,47(6):194-199.
[32] Tang Youzhi,Liu Yahong.Progress in research of carbon nanotubes as drug carriers[J].Chinese Journal of Veterinary Science,2012,32(10):1587-1591(in Chinese).汤有志,刘雅红.碳纳米管作为药物载体的研究进展[J].中国兽医学报,2012,32(10):1587-1591.
[33] Yu B,Tan L,Zheng R,et al.Targeted delivery and controlled release of paclitaxel for the treatment of lung cancer using single-walled carbon nanotubes[J].Materials Science&Engineering C Materials for Biological Applications,2016,68:579-584.
[34] Gan Li,Yan Xuebin,Zhang Raoxiang,et al.Preparation of functionalized single-walled carbon nanotubes/NR2B-shRNA interference plasmid complex and its application in gene therapy for chronic pain[J].Chinese Journal of Pain Medicine,2013,19(4):220-224(in Chinese).甘丽,阎雪彬,章饶香,等.功能化单壁碳纳米管/NR2B-shRNA干扰质粒复合物的制备及其用于慢性疼痛的基因治疗[J].中国疼痛医学杂志,2013,19(4):220-224.
[35] Gu Xiaoxiao,Du Baoji,Li Yunhui,et al.Vectors based on nanomaterials for gene delivery[J].Progress in Chemistry,2015,27(8):1093-1101(in Chinese).古晓晓,杜宝吉,李云辉,等.基于纳米材料的基因载体[J].化学进展,2015,27(8):1093-1101.
[36] Huang Shuwen.Preparation and characterization of biodegradable polyethylenimine grafted carbon nanotubes as gene vector[D].Wuhan:Wuhan Institute of Technology,2015(in Chinese).黄书文.碳纳米管接枝可降解聚乙烯亚胺基因载体的制备与表征[D].武汉:武汉工程大学,2015.
[37] Wang Yue,Wang Peng,Chen Chunying,et al.Cellular and molecular mechanisms of pulmonary toxicity caused by carbon nanotubes with various physiochemical properties[J].Chinese Science Bulletin,2013,58(21):2007-2020(in Chinese).王越,王鹏,陈春英,等.碳纳米管呼吸系统毒性作用机制及其影响因素的研究进展[J].科学通报,2013,58(21):2007-2020.
[38] Liu Yuanfang,Liu Jiahui,Wang Haifang.Cytotoxicity of pristine carbon nanotubes:mechanism and influencing factors[J].Journal of Shanghai University(Natural Science Edition),2010,16(5):447-459(in Chinese).刘元方,刘佳蕙,王海芳.未修饰碳纳米管的细胞毒性机理及其影响因素[J].上海大学学报(自然科学版),2010,16(5):447-459.
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