再生静电纺丝素纳米纤维在面神经修复中作用的实验研究
|
摘要
目的：研究再生静电纺丝素纳米纤维导管能否为面神经修复提供适宜的再生微环境，促进和引导面神经再生，探讨其成为面神经缺损桥接替代物的可行性，为临床应用提供实验依据。
方法：首先采用静电纺丝方法制备再生丝素纳米纤维网：直径305±84nm，呈纤维状三维立体结构，纤维分布均匀横向排列；其次制备再生静电纺丝素纳米纤维导管：导管内径1.5mm，0.2mm厚。最后上述材料经乙醇处理、蒸馏水三次洗涤和辐照后备用。1.体外实验：施旺细胞培养：取出生1～2d的新生SD大鼠背根脊神经节（DRG），Hanks缓冲液内剥离外膜，双酶消化后以1×105/孔密度接种在制备好的丝素蛋白膜（SF）和多聚赖氨酸（PLL）包被的35mm培养皿上，倒置相差、激光共聚焦、扫描电子显微镜下观察施旺细胞粘附、生长、迁移情况，并分别对施旺细胞增殖活力（MTT试验）及其分泌三种神经营养因子(CNTF、BDNF、NGF)的蛋白表达水平（ELISA）进行测试。2.体内实验：建立SD大鼠面神经损伤修复模型：横断右侧面神经形成5mm缺损；自体面神经、再生静电纺丝素纳米纤维导管分别桥接5mm缺损的面神经，3月后进行再生面神经功能评估，包括Flurogold（FG）逆行追踪、面神经电生理测试及再生髓鞘厚度、直径的测定。
结果：1.从倒置相差、激光共聚焦、扫描电子显微镜结果来看：与对照组（PLL）相比，305nm再生静电纺丝素纳米纤维更适合大鼠施旺细胞的贴附、增殖、生长,对细胞迁移起引导作用，在静电纺丝素蛋白纳米纤维上施旺细胞间的排列更有序、细胞突起彼此能够形成更广泛、复杂的网状突触连接；而因为没有丝素蛋白纳米纤维支持，在PLL上的细胞排列相对简单、分布随机，突触间连接距离相对短；MTT和ELISA结果表明该材料对施旺细胞增殖活力及分泌三种神经营养因子(CNTF、BDNF、NGF)的功能没有影响。2.该材料制成的导管植入SD大鼠体内无明显不良反应，3个月就已经完全被吸收降解，缺损的面神经穿过导管重新连接在一起；从移植3月后进行神经电图（ENOG）所监测面神经复合动作电位（CMAPs）的波幅及潜伏期变化情况，可以看到面神经功能得到一定程度的恢复，尽管材料组的CMAPs波幅明显低于正常对照组，但与自体面神经移植组相比，CMAPs波幅和潜伏期方面没有显著统计学差异（P>0.05）；超微结构发现两实验组再生髓鞘的厚度和直径无显著统计学差异（P>0.05）；我们在材料及自体面神经移植组移植同侧的大鼠脑干面神经核团内发现荧光金逆行示踪剂出现，而阴性对照组（神经切断未再生）的面神经核团内未见荧光金逆行示踪剂出现，比较两实验组有荧光金标记的面运动神经元数量无显著性统计学差异(P>0.05)。
结论：再生静电纺丝素纳米纤维能够为施旺细胞的黏附、生长、迁移提供良好的生长表面，丝素纤维的分布与走向对细胞的黏附、铺展、分布、突起方向及迁移起引导作用，从而为神经轴突的生长提供更适宜的生长通道，引导和促进轴突的定向生长；静电纺丝素纳米纤维导管能引导再生面神经通过缺损区域与远端连接，再生面神经的功能可以得到部分恢复，能够取代自体神经移植修复面神经缺损，具有潜在的临床应用价值。
Objective: To research whether regenerated electrospun silk fibroin nanofibers（SF）as never conduits could improve nerve regeneration microenvironment and induce thefacial never regeneration of SD rats or not. Its feasibility as a kind of novel graft forassisting the regeneration process of defects in the facial never was explored in order toprovide experimental evidence for clinical use.
Methods:Firstly, fabrication of silk fibroin nanofibrous scaffolds：the nanofibershad a smooth surface with solid voids among the fibers, interconnecting a porousnetwork, constituting a fibriform three-dimensional structure and that the averagediameter of the fibers was about305±84nm; Secondly, preparation of SF nanofibergrafts: the SF nanofiber tubes had a bilayered structure with aligned nanofibers in theinner layer, and random nanofibers in the outer layer.The inner diameter is1.5mm and0.2mm thickness.Last, both were immersed in75%ethanol,dried in vacuum at roomtemperature,sterilized by radiation prior to use.1. In vitro：Schwanns cell (SCs) culture:the rat dorsal root ganglia （DRG） of neonatal SD rats with1–2d old,stripped in Hank’sbalanced salt solution, at the density of1.0×105cells/well seeded on the pre-wetted SFand poly-L-lysine（PLL）-coated cover slips in35mm Petri dishes respectively aftertrypsinized. Schwanns cell adhesion, growth and immigration were observed underinverted light microscopy， fluorescence microscope and scanning electronmicrograph(SEM). Schwanns cell proliferation viability examination by MTT and cellprotein expression examination(ELISA) about neurotrophic factors (CNTF、BDNF、NGF)were analysed.2. In vivo: Set up the animal surgery models: the facial nerve transectedleaving a5-mm long defect was bridged with SF graft or autograft in SD rats.Three months after implantation, morphological and functional evaluation that includedelectrophysiology, histology, Fluorogold retrograde tracing and transmission electronmicrographs were carried through in terms of nerve repair.
Results：1. From SEM, light and fluorescence microscopy we observed longer cellprotrusions and network formation of SCs on the random electrospun SF. SCs formed amore effective and complex interconnecting network through the longer neurites. Incontrast, in the absence of the topographical guide of the scaffold, SCs cultured on PLLadopted an unorganized, disordered morphology with a random orientation. A greaternumber of cells on SF extended tightly along the silk scaffolds forming longer cell chainsthan on PLL which is the basis of regenerating axons across a nerve gap graft to a distalaxon. On the other hand,according to the results of MTT and ELISA, this material did notexert any significant cytotoxic effects on their phenotype and had no any negativeinfluence on expression of neurotrophic factors at protein level.2. In vivo：The effects ofnerve regeneration were observed by a range of morphological and functional assessments.There were no distinct regional inflammation response and scar formation in the rats in theSF graft group over a3-month period after implantation, similar changes were observed inthe autograft group. At3months after implantation, the SF graft had disappeared due todegradation, and the original5-mm long nerve defect was replaced with a tissue that had anerve-like appearance between both stumps. CMAPs amplitude has decreased significantlywhen compared with the normal CMAPs amplitude value recorded at the contralateralunoperated side, there was no significant difference between the SF graft and autograftgroups. The FG retrograde tracings were found in the facial nucleus ipsilateral to theoperated side of the rats in the SF graft and autograft groups. Moreover, statistical analysisshowed that there was no significant difference in the morphometric data, including theaverage thickness of regenerated myelin sheaths, the mean diameter of myelinated fibers,the number of retrograde-labeled motoneurons and the CMAPs amplitudes between thesilk fibroin graft and autograft groups(P>0.05).
Conclusions: Regenerated electrospun silk fibroin nanofibers was beneficial to the adherence, proliferation and migration of SCs. The distribution of nanofibrous scaffoldscould serve as a suitable substrate for cell spreading、neurites extending, which offered thenerve regeneration channels under the topographical guide of the scaffold.The SF tubecould induce the nerve stump across the facial never gap defect, and regenerated nervefibers in SF group succeeded in reconnection. Hence regenerated electrospun silk fibroinnanofibers could replace nerve autografts to facilitate nerve repair following facial nerveinjury and maybe become a promising alternative in repairing peripheral neural structureand function. It was of potential value in clinical applications.
方法：首先采用静电纺丝方法制备再生丝素纳米纤维网：直径305±84nm，呈纤维状三维立体结构，纤维分布均匀横向排列；其次制备再生静电纺丝素纳米纤维导管：导管内径1.5mm，0.2mm厚。最后上述材料经乙醇处理、蒸馏水三次洗涤和辐照后备用。1.体外实验：施旺细胞培养：取出生1～2d的新生SD大鼠背根脊神经节（DRG），Hanks缓冲液内剥离外膜，双酶消化后以1×105/孔密度接种在制备好的丝素蛋白膜（SF）和多聚赖氨酸（PLL）包被的35mm培养皿上，倒置相差、激光共聚焦、扫描电子显微镜下观察施旺细胞粘附、生长、迁移情况，并分别对施旺细胞增殖活力（MTT试验）及其分泌三种神经营养因子(CNTF、BDNF、NGF)的蛋白表达水平（ELISA）进行测试。2.体内实验：建立SD大鼠面神经损伤修复模型：横断右侧面神经形成5mm缺损；自体面神经、再生静电纺丝素纳米纤维导管分别桥接5mm缺损的面神经，3月后进行再生面神经功能评估，包括Flurogold（FG）逆行追踪、面神经电生理测试及再生髓鞘厚度、直径的测定。
结果：1.从倒置相差、激光共聚焦、扫描电子显微镜结果来看：与对照组（PLL）相比，305nm再生静电纺丝素纳米纤维更适合大鼠施旺细胞的贴附、增殖、生长,对细胞迁移起引导作用，在静电纺丝素蛋白纳米纤维上施旺细胞间的排列更有序、细胞突起彼此能够形成更广泛、复杂的网状突触连接；而因为没有丝素蛋白纳米纤维支持，在PLL上的细胞排列相对简单、分布随机，突触间连接距离相对短；MTT和ELISA结果表明该材料对施旺细胞增殖活力及分泌三种神经营养因子(CNTF、BDNF、NGF)的功能没有影响。2.该材料制成的导管植入SD大鼠体内无明显不良反应，3个月就已经完全被吸收降解，缺损的面神经穿过导管重新连接在一起；从移植3月后进行神经电图（ENOG）所监测面神经复合动作电位（CMAPs）的波幅及潜伏期变化情况，可以看到面神经功能得到一定程度的恢复，尽管材料组的CMAPs波幅明显低于正常对照组，但与自体面神经移植组相比，CMAPs波幅和潜伏期方面没有显著统计学差异（P>0.05）；超微结构发现两实验组再生髓鞘的厚度和直径无显著统计学差异（P>0.05）；我们在材料及自体面神经移植组移植同侧的大鼠脑干面神经核团内发现荧光金逆行示踪剂出现，而阴性对照组（神经切断未再生）的面神经核团内未见荧光金逆行示踪剂出现，比较两实验组有荧光金标记的面运动神经元数量无显著性统计学差异(P>0.05)。
结论：再生静电纺丝素纳米纤维能够为施旺细胞的黏附、生长、迁移提供良好的生长表面，丝素纤维的分布与走向对细胞的黏附、铺展、分布、突起方向及迁移起引导作用，从而为神经轴突的生长提供更适宜的生长通道，引导和促进轴突的定向生长；静电纺丝素纳米纤维导管能引导再生面神经通过缺损区域与远端连接，再生面神经的功能可以得到部分恢复，能够取代自体神经移植修复面神经缺损，具有潜在的临床应用价值。
Objective: To research whether regenerated electrospun silk fibroin nanofibers（SF）as never conduits could improve nerve regeneration microenvironment and induce thefacial never regeneration of SD rats or not. Its feasibility as a kind of novel graft forassisting the regeneration process of defects in the facial never was explored in order toprovide experimental evidence for clinical use.
Methods:Firstly, fabrication of silk fibroin nanofibrous scaffolds：the nanofibershad a smooth surface with solid voids among the fibers, interconnecting a porousnetwork, constituting a fibriform three-dimensional structure and that the averagediameter of the fibers was about305±84nm; Secondly, preparation of SF nanofibergrafts: the SF nanofiber tubes had a bilayered structure with aligned nanofibers in theinner layer, and random nanofibers in the outer layer.The inner diameter is1.5mm and0.2mm thickness.Last, both were immersed in75%ethanol,dried in vacuum at roomtemperature,sterilized by radiation prior to use.1. In vitro：Schwanns cell (SCs) culture:the rat dorsal root ganglia （DRG） of neonatal SD rats with1–2d old,stripped in Hank’sbalanced salt solution, at the density of1.0×105cells/well seeded on the pre-wetted SFand poly-L-lysine（PLL）-coated cover slips in35mm Petri dishes respectively aftertrypsinized. Schwanns cell adhesion, growth and immigration were observed underinverted light microscopy， fluorescence microscope and scanning electronmicrograph(SEM). Schwanns cell proliferation viability examination by MTT and cellprotein expression examination(ELISA) about neurotrophic factors (CNTF、BDNF、NGF)were analysed.2. In vivo: Set up the animal surgery models: the facial nerve transectedleaving a5-mm long defect was bridged with SF graft or autograft in SD rats.Three months after implantation, morphological and functional evaluation that includedelectrophysiology, histology, Fluorogold retrograde tracing and transmission electronmicrographs were carried through in terms of nerve repair.
Results：1. From SEM, light and fluorescence microscopy we observed longer cellprotrusions and network formation of SCs on the random electrospun SF. SCs formed amore effective and complex interconnecting network through the longer neurites. Incontrast, in the absence of the topographical guide of the scaffold, SCs cultured on PLLadopted an unorganized, disordered morphology with a random orientation. A greaternumber of cells on SF extended tightly along the silk scaffolds forming longer cell chainsthan on PLL which is the basis of regenerating axons across a nerve gap graft to a distalaxon. On the other hand,according to the results of MTT and ELISA, this material did notexert any significant cytotoxic effects on their phenotype and had no any negativeinfluence on expression of neurotrophic factors at protein level.2. In vivo：The effects ofnerve regeneration were observed by a range of morphological and functional assessments.There were no distinct regional inflammation response and scar formation in the rats in theSF graft group over a3-month period after implantation, similar changes were observed inthe autograft group. At3months after implantation, the SF graft had disappeared due todegradation, and the original5-mm long nerve defect was replaced with a tissue that had anerve-like appearance between both stumps. CMAPs amplitude has decreased significantlywhen compared with the normal CMAPs amplitude value recorded at the contralateralunoperated side, there was no significant difference between the SF graft and autograftgroups. The FG retrograde tracings were found in the facial nucleus ipsilateral to theoperated side of the rats in the SF graft and autograft groups. Moreover, statistical analysisshowed that there was no significant difference in the morphometric data, including theaverage thickness of regenerated myelin sheaths, the mean diameter of myelinated fibers,the number of retrograde-labeled motoneurons and the CMAPs amplitudes between thesilk fibroin graft and autograft groups(P>0.05).
Conclusions: Regenerated electrospun silk fibroin nanofibers was beneficial to the adherence, proliferation and migration of SCs. The distribution of nanofibrous scaffoldscould serve as a suitable substrate for cell spreading、neurites extending, which offered thenerve regeneration channels under the topographical guide of the scaffold.The SF tubecould induce the nerve stump across the facial never gap defect, and regenerated nervefibers in SF group succeeded in reconnection. Hence regenerated electrospun silk fibroinnanofibers could replace nerve autografts to facilitate nerve repair following facial nerveinjury and maybe become a promising alternative in repairing peripheral neural structureand function. It was of potential value in clinical applications.
引文
[1] Cheng C, Zochodne DW. In vivo proliferation，migration and phenotypic changes ofSchwann cells in the prsents of myelinated fibers. Neuroscience2002;115:321-329．
[2] Luke E. Role of the Schwann cell in diabetic neuropathy. International review ofNeurobiology2002;50:293-312.
[3] Evans GR. Peripheral never injury. A review and approach to tissue andengineering conducts. Anat Rec2001;263:396-404.
[4]陈菁,楚燕飞,顾玉东,等.培养施旺细胞NGF、CNTF和GDNF共表达和共定位实验研究.中华手外科杂志2005;21:317-319.
[5]何继银,劳杰,蒋良福,等.激活态施旺细胞信号转导通路的初步研究.中华手外科杂志2006;22:376-378.
[6] Rhona Mirskya, Kristjan R. Jessena, Angela Brennana,et al. Schwann cells asregulators of nerve development.Journal of physiology-Paris2002;(96):17-24.
[7] Burnett MG,Zager EL. Pathophysiology of peripheral nerve injury: a brief review[J].Neurosurg Focus2004;16(5):1-7.
[8] Bünge R.P. Expanding roles for the Schwann cell: ensheathment, myelination,trophism and regeneration. Curr. Opin. Neurobiol1993;3:805-809.
[9] Jessen K.R, Mirsky R. Schwann cells and their precursors emerge as majorregulators ofnerve development. Trends Neurosci1999;22:402-410.
[10] Singer A.J, Clark R.A. Cutaneous wound healing. N. Engl. J. Med1999;341:738-746.
[11] Sendtner M, Holtmann B, Kolbeck R, Thoenen H, Barde Y.A. Brain-derivedneurotrophic factor prevents the death of motoneurons in newborn rats after nervesection. Nature1992;360:757-759.
[12] Hoke A., Cheng C, Zochodne D.W. Expression of glial cell line-derivedneurotrophic factor family of growth factors in peripheral nerve injury in rats.NeuroReport2000;11:1651-1654.
[13] Meyer M, Matsuoka I, Wetmore C, Olson L, Thoenen H. Enhanced synthesisofbrain-derived neurotrophic factor in the lesioned peripheral nerve: differentmechanisms are responsible for the regulation of BDNF and NGF mRNA. J. Cell Biol1992;119:45-54.
[14]宋涛,伶晓杰.施旺细胞与周围神经再生.解剖科学进展2000;6(1):27-2.
[15] Daniel GO. Gila—neuron crosstalk in the neuroprotective mechanisms of sex steroidhormones.Brain Res Brain Res Rev2005;48:273-286.
[16] Cheng C, Qin YW, Shao XY,et al. Induction of TNF-a by LPS in Schwann Cellis Regulated by MAPK Activation Signals. Cell Mol Neurobiol2007;27:909–921.
[17] Cochan M.Schwann cell fail to differentiate when co-culture in contact with PC12neurites.Brain Res1985;351:89-93.
[18] Wood PM.Separation of functioned Schwann cells and neurons from normalperipheral nerve tissue.Brain Res1976;115:361-375.
[19] Brockes JP,Fields KL,Reff MC.Studies on cultured rat Schwann cells. Establishmentof purified population from cultures of peripheral nerve. Brain Res1979;165:105-118.
[20] Xu XM,Guenard V, Kleitman N. Axonal regeneration into Schwann cell-seededguidance channels grafted into transected adult rat spine cord.J Compara Neurol1995;351:145-160.
[21]连小峰,侯铁胜,傅强,等.植块法与酶消化法结合培养原代大鼠施旺细胞.中国脊柱脊髓杂志2008;18（9）:703-706.
[22]何晶,李锋,丁文龙.施旺氏细胞体外培养不同方法的比较.解剖学杂志2006;29（3）:384-386.
[23]黄小强,罗卓荆,李明全.新生SD大鼠坐骨神经施旺细胞培养与纯化的方法学研究.中华创伤骨科杂志2005;7（4）:341-343.
[24] Askanas V. Engel WK，Dalakas MC，et a1. Human schwann cells in tissue culture：histochemical and uhrastructural studies. J.Arch Neurol1980;37(6):329—337．
[25]洪坦辉,金羽青,戴传昌,等.复合胶原酶消化法制备高纯度小鼠雪旺细胞.组织工程与重建外科杂志2008;5(4):259-263.
[26]胡唏棠,熊良俭,劳杰.从成年大白鼠坐骨神经分离培养许旺细胞的方法学探讨.中华显微外科杂志2002;25(3):197-200.
[27] Kreider BQ, Messing A, Doan H.Enrichment of Schwanncell cultures from neonatalrat sciatic nerve by difIerential adhesion. Brain Res1981;207：433-449.
[28] Assouline JG, Bosch EP, Lim R. Purification of rat Schwann cells from cultures ofperipheral nerve: an immunoseleetive method using surfaces coatedantiimmunoglobun antibodies. Brain Res1983;227:389．
[29]孙晓红,窦文波,佟晓杰,等.许旺细胞与脱细胞神经移植物共培养在周围神经损伤修复中的作用.中国临床康复2006;29(10):19-21.
[30]朱伟,侍坚,路长林.新生大鼠雪旺细胞体外培养及纯化的方法比较.海军医学杂志2001;22(3):202-205.
[1] Burkhard S, Erhard M, Bernhard S, et al. Rat Schwann cells in bioresorbable nerveguides to promote and accelerate axonal regeneration. Brain Research2003;963:321-326.
[2] Christine E, Jennie B. Neural tissue engineering: Strategies for Repair andregeneration. Annu Rev Biomed Eng2003;5:293-347.
[3] Panseri S, Cunha C, Lowery J, Del Carro U, Taraballi F, Amadio S, et al.Electrospun micro-and nanofiber tubes for functional nervousregeneration in sciatic nerve transections. BMC Biotechnol2008;8:39.
[4] Cunha C, Panseri S, Antonini S．Emerging nanotechnology approaches in tissueengineering for peripheral nerve regeneration．Nanomedicine2011;(7):50–59.
[5] Yang YM, Chen XM, Ding F, et al. Biocompatibility evaluation of silk fibroin withperipheral nerve tissues and cells in vitro. Biomaterials2007;28:1643-1652.
[6] Chen XM, Yang YM, Wu J, et al. Biocompatibility studies of silk fibroin-basedartificial nerve grafts in vitro and in vivo. Prog Natur Sci2007;17(9):1029-1034.
[7] Yang YM, Wu J, Ding F, et al. Development and evaluation of silk fibroin-basednerve grafts used for peripheral nerve regeneration. Biomaterials2007;28:5526-5535.
[8]陆艳,迟放鲁,赵霞,等.丝素导管修复面神经缺损的实验研究.中华耳鼻咽喉头颈外科杂志2006;41（8）:603-606.
[9] Borys B, Sabine F, Charles J. K. et al. Functionality of endothelial cells on silkfibroin nets: Comparative study of micro-and nanometric fibre size. Biomaterials2008;29（5）:561-572.
[10] Ki CS, Park SY, Kim HJ, et al. Development of3-D nanofibrous fibroin scaffoldwith high porosity by electrospinning: implications for bone regeneration[J].Biotechnol Lett2008;30:405–410.
[11] Gupta D, Venugopal J, Prabhakaran MP, et al. Aligned and random nanofibroussubstrate for the in vitro culture of Schwann Cells for neural tissue engineering[J].Acta Biomaterialia2009;5(7):2560-2569.
[12] Martin CR. Membrane-based synthesis of nanomaterials. Chem Mater1996;8:1739-1746.
[13] Feng L, Li S, Li Y, et al. Super-hydrophobic surfaces: from natural to artificial. AdvMater2002;14(24):1857-1860.
[14] Fan YY, Cheng HM, Wei YL, et al. Tailoring the diameters of vapor-grown carbonnanofibers. Carbon2000;38:789-795.
[15] Ma PX, Zhang R. Microtubular architecture of biodegradable polymerscaffolds. J Biochem Mater Res Part A2001;56:469-77.
[16] Ondarcuhu T, Joachim C. Drawing a single nanofibre over hundreds of microns.Europhys Lett1998;42:215-220.
[17] Huang ZM, Zhang YZ, Kotaki M, et al. A review on polymer nanofibers byelectrospinning and their applications in nanocomposites[J]. Compos Sci Technol2003;63(15):2223-2253.
[18] Vleggeert-Lankamp CL, et al. Adhesion and proliferation of human Schwann cellson adhesive coatings. Biomaterials2004;25(14):2741–2751.
[19] Wang GL,Hu XD,Wei Lin et al. Electrospun PLGA–silk fibroin–collagennanofibrous scaffolds for nerve tissue engineering. Biol.—Animal2011;47:234–240.
[20] Ghasemi-Mobarakeh M, et al. Electrospun poly (3-caprolactone)/gelatinnanofibrous scaffolds for nerve tissue engineering.Biomaterials2008;29(34):4532–4539.
[21] Wang Y, Rudym DD, Walsh A, et al. In vivo degradation of threedimensional silkfibroin scaffolds. Biomaterials2008;29(24-25):3415-3428.
[22] Pham QP, Sharma U, Mikos AG. Electrospinning of polymeric nanofibers fortissue engineering applications: A review. Tissue Eng2006;12(5):1197-211.
[23] Lawrence BD, Marchant JK, Pindrus MA, et al. Silk film biomaterials for corneatissue engineering. Biomaterials2009;30(7):1299-1308.
[24] Murphy AR, St John P, Kaplan DL. Modification of silk fibroin using diazoniumcoupling chemistry and the effects on hMSC proliferation and differentiation.Biomaterials2008;29(19):2829-2838.
[25] Jin HJ, Chen J, Karageorgiou V, et al. Human bone marrow stromal cell responseson electrospun silk fibroin mats. Biomaterials2004;25(6):1039-1047.
[26] Wang X, Zhang X, Castellot J, et al. Controlled release from multilayer silkbiomaterial coatings to modulate vascular cell responses. Biomaterials2008;29(7):894-903.
[27] Zhang X, Baughman CB, Kaplan DL. In vitro evaluation of electrospun silk fibroinscaffolds for vascular cell growth. Biomaterials2008;29(14):2217-2227.
[28] Yang Y, Ding F, Wu J, et al. Development and evaluation of silk fibroin-basednerve grafts used for peri pheral nerve regeneration. Biomaterials2007;28(36):5526-5535.
[29] Zhang F, Qin JZ, Liu R, et al. Electrospun silk fibroin nanofiber tubes forperipheral nerve regeneration. ICBBE2010.
[30] Yim EKF, Leong KW. Significance of synthetic nanostructures in dictating cellularresponse. Nanomed Nanotechnol Biol Med2005;1:10–21.
[31] Chen CS, Mrksich M, Huang S, Whitesides GM, Ingber DE. Micropatternedsurfaces for control of cell shape, position and function. Biotechnology1998;14:356–63.
[32] Dalby MJ, Riehle MO, Yarwood SJ, Wilkinson CDW, Curtis ASG. Nucleusalignment and cell signaling in fibroblasts: response to a micro-groovedtopography.Exp Cell Res2003;284:274–82.
[33] Cunha C, Panseri S, Antonini S．Emerging nanotechnology approaches in tissueengineering for peripheral nerve regeneration．Nanomedicine2011;(7):50–59.
[34] Chew SY, Mi R, Hoke A, Leong KW. Aligned protein-polymer composite fibersenhance nerve regeneration: a potential tissue engineering platform. Adv Funct Mater2007;17:1288–96.
[35] Ogata T, Yamamoto SI, Nakamura K,Tanaka S. Signaling axis in Schwann cellproliferation and differentiation. Mol Neurobiol2006;33:51–61.
[36] Sing Yian Chew, Ruifa Mi, Ahmet Hoke. The effect of the alignment ofelectrospun fibrous scaffolds on Schwann cell maturation. Biomaterials2008;29:653–661.
[37] Yang F, Murugan R, Wang S, Ramakrishna S. Electrospinning of nano/micro scale poly(L-lactic acid) aligned fibers and their potential in neural tissueengineering. Biomaterials2005;26:2603-10.
[38] Klein R. Role of neurotrophins in mouse neuronal development. FASEB J1994;8(10):738–44.
[39] Yin Q, Kemp GJ, Frostick SP. Neurotrophins, neurones and peripheral nerveregeneration. J Hand Surg1998;23(4):433–7.
[40] Frostick SP, Yin Q, Kemp GJ. Schwann cells, neurotrophic factors and peripheralnerve regeneration. Microsurgery1998;18(7):397–405.
[41] Anand U, Otto WR, Casula MA, Day NC, Davis JB, Bountra C,et al. The effect ofneurotrophic factors on morphology, TRPV1expression and capsaicin responses ofcultured human DRG sensory neurons. Neurosci Lett2006;399(1–2):51–6.
[42] Moore K, MacSween M, Shoichet M. Immobilized concentration gradients Ofneurotrophic factors guide neurite outgrowth of primary neurons in Macroporousscaffolds. Tissue Eng2006;12(2):267–78.
[43] Hadlock T, Elisseeff J, Langer R, Vacanti J, Cheney M. A Tissueengineeredconduit for peripheral nerve repair. Arch Otolaryngol Head Neck Surg1998;124:1081–86.
[44]董运海，张锋，左保齐,等.再生丝素蛋白纳米纤维网支持和引导神经胶质细胞的生长与迁移.中国生物医学工程学报2009;28（1）:96-102，116.
[1] Cao H, Liu T, Chew SY. The application of nanofibrous scaffolds in neural tissueengineering. Adv Drug Deliv Rev2009;61(12):1055-64.
[2] Schmidt CE, Leach JB. Neural tissue engineering: strategies for repair andregeneration. Annu Rev Biomed2003;5:293–347.
[3] Schmidt CE, Shastri VR, Vacanti JP, et al. Stimulation of neurite outgrowth using anelectrically conducting polymer. Proc Natl Acad Sci1997;94:8948–8953.
[4] Beris A, Lykissas M, Korompilias A, Mitsionis G. End-to-side nerve repair inperipheral nerve injury. J Neurotrauma2007;24(5):909-16.
[5] Thomas F, Rivelino M, Hui SK, Molly SS. Chitin-based tubes for tissue engineeringin the nervous system. Biomaterials2005;26:4624–32.
[6] Wang X, Hu W, Cao Y, Yao J, Wu J, Gu X. Dog sciatic nerve regeneration across a30-mm defect bridged by a chitosan/PGA artificial nerve graft. Brain2005;128:1897–910.
[7] Bellamkonda RV. Peripheral nerve regeneration: an opinion on channels scaffoldsand anisotropy. Biomaterials2006;27:3515-8.
[8] Jiang BG, Yin XF, Zhang DY, Fu ZG, Zhang HB. Maximum number of collateralsdeveloped by one axon during peripheral nerve regeneration and the influence of thatnumber on reinnervation effects. Eur Neurol2007;58:12–20.
[9] Bini T.B, Gao Shujun, Wang Shu Ramakrishna S. Poly(l-lactide-co-glycolide)biodegradable microfibers and electrospun nanofibers for nerve tissue engineering: anin vitro study. Journal of Materials Science2006;41(19):6453-9）
[10] Huang YC, Huang YY. Tissue engineering for nerve repair. Biomed Eng ApplicBasis2006;18:100–110.
[11] Li C, Vepari C, Jin HJ, Kim HJ, Kaplan DL. Electrospun silk-BMP-2scaffolds forbone tissue engineering. Biomaterials2006;27(16):3115–24.
[12] Li J, He A, Zheng J, Han CC. Gelatin and gelatin-hyaluronic acid nanofibrousmembranes produced by electrospinning of their aqueoussolutions.Biomacromolecules2006;7(7):2243-7.
[13] Patel M, VandeVord PJ, Matthew HW, et al. Collagen-chitosan nerve guides forperipheral nerve repair: a histomorphometric study. J Biomater Appl2008;23(2):101-21.
[14] Gupta D, Venugopal J, Prabhakaran MP, Dev VR, Low S, Choon AT, Ramakrishna S.Aligned and random nanofibrous substrate for the in vitro culture of Schwann cellsfor neural tissue engineering. Acta Biomater2009;5(7):2560-9.
[15] Schnell E, Klinkhammer K, Balzer S, Brook G, Klee D, Dalton P, et al.Guidance ofglial cell migration and axonal growth on electrospun nanofibers ofpoly--caprolactone and a collagen/poly--caprolactone blend. Biomaterials2007;28:3012-25.
[16] Koh HS, Yong T, Chan CK, Ramakrishna S. Enhancement of neurite outgrowthusing nano-structured scaffolds coupled with laminin.Biomaterials2008;29:3574-82.
[17] Gelain F, Bottai D, Vescovi A, Zhang S. Designer self-assembling peptide nanofiberscaffolds for adult mouse neural stem cell3-dimensional cultures. PLoS ONE2006;e119:1.
[18] Cunha C, Panseri S, Antonini S．Emerging nanotechnology approaches in tissueengineering for peripheral nerve regeneration．Nanomedicine2011；(7):50–59.
[19] Yamada H, Igarashi Y, Takasu Y, et al. Identifi cation of fi broin-derived peptidesenhancing the proliferation of cultured human skin fi broblasts.Biomaterials2004;25(3):467-472.
[20] Kim SH, Nam YS, Lee TS, et al. Silk Fibroin Nanofiber. Electrospinning, Properties,and Structure. Polymer Journal2003;35:185-190.
[21] Li M, Ogiso M, Minoura N. Enzymatic degradation behavior of porous silk fibroinsheets. Biomaterias2003;24(2):357-365.
[22] Yang Y, Ding F, Wu J, Hu W, Liu W, Liu J, Gu X. Development and evaluation ofsilk fibroin-based nerve grafts used for peripheral nerve regeneration.Biomaterials2007;28(36):5526-35.
[23] Min BM, You Y, Kim JM, et al. Formation of nanostructured poly (lactic-co-glycolicacid)/chitin matrix and its cellular response to normal human keratinocytes andfibroblasts. Carbohydr Polym2004;57:285-292.
[24] Sill TJ, von Recum HA. Electrospinning: applications in drug delivery and tissueengineering. Biomaterials2008;29(13):1989-2006.
[25] Ashammakhi N, Wimpenny I, Nikkola L, Yang Y. Electrospinning: methods anddevelopment of biodegradable nanofibres for drug release. J Biomed Nanotechnol2009;5(1):1-19.
[26] Bechara SL, Judson A, Popat KC. Template synthesized poly(epsilon-caprolactone)nanowire surfaces for neural tissue engineering. Biomaterials2010;31(13):3492-501.
[27] Shahmoon A, Limon O, Girshevitz O, Zalevsky Z. Self assembly of nano metricmetallic particles for realization of photonic and electronic nano transistors.Int J MolSci2010;11(5):2241-52.
[28] Liu X, Ma PX. The nanofibrous architecture of poly(L-lactic acid)-based functionalcopolymers. Biomaterials2010;31(2):259-69.
[29] Ahmed J, Varshney SK, Auras R. Rheological and thermal properties ofpolylactide/silicate nanocomposites films. Food Sci2010;75(2):17-24.
[30] Kumbar SG, James R, Nukavarapu SP, Laurencin CT. Electrospun nanofiberscaffolds: engineering soft tissues. Biomed Mater2008;3(3):034002.
[31] Zhang YZ, Su B, Venugopal J, Ramakrishna S, Lim CT. Biomimetic and bioactivenanofibrous scaffolds from electrospun composite nanofibers. Int J Nanomedicine2007;2(4):623-38.
[32] Xu CY, Inaic R, Kotaki M. Aligned biodegradable nanofibrous structure: a potentialscaffold for blood vessel engineering. Biomaterials2004;25:877-886.
[33] Ju YW, Choi GR, Jung HR. Electrochemical properties of electrospun PAN/MWCNTcarbon nanofibers electrodes coated with polypyrrole. Electrochimica Acta2008;53(19):5796-5803.
[34] Shin MK, Kim YJ, Kim SI. Enhanced conductivity of aligned PANi/PEO/MWNTnanofbers by electrospinning. Sens Actuators B2008;134:122-126.
[35] Dalton PD, Klee D, Moller M. Electrospinning with dual collection rings. Polymer2005;46:611-614.
[36] Xin Yi, Huang Zonghao, Chen Jinfeng. Fabrication of well-aligned PPV/PVPnanofibers by electrospinning. Mater Lett，2008，62:991-993.
[37] Baker Brendon M., Mauck Robert L. The effect of nanofiber alignment on thematuration of engineered meniscus constructs. Biomaterials2007;28:1967-1977.
[38] Yu J, Qiu YJ, Zha XX, et al. Production of aligned helical polymer nanofbers byelectrospinning[J]. Eur Polym2008;44(9):2838-2844.
[39]周文,陈新,邵正中.红外和拉曼光谱用于对丝蛋白构象的研究[J].化学进展2006;18（11）:1514-1522.
[40] Hu AJ, Zuo BQ, Zhang F, Zhang HX, Lan Q. Biocompatibility evaluation ofelectrospun silk fibroin nanofibers with Schwann cells in vitro. Advanced MaterialsResearch2011;175-176:220-223.
[41] Wang Y, Kim HJ, Vunjak-Novakovic G, Kaplan DL. Stem cellbased tissueengineering with silk biomaterials. Biomaterials2006;August4,Epub ahead of print.
[42] Yang F, Murugan R., Ramakrishna S, Wang X, Ma YX, Wang S. Fabrication ofnano-structured porous PLLA scaffold intended for nerve tissue engineering.Biomaterials2004;25:1891-900.
[43] Wen X, Tresco PA. Effect of filament diameter and extracellular matrix moleculeprecoating on neurite outgrowth and Schwann cell behavior on multifilamententubulation bridging device in vitro. J Biomed Mater Res2006;76A:626–37.
[44] Dyck PJ, Thomas PK.Peripheralneuropathy.Philadelphia: W.B.Saunders Co1993;290-298.
[45] Baron-Van Evercooren A, Avellana-Adalid V, Lachapelle F, et a1. Schwann celltransplantation and myelin repair of the CNS[J]．Mult Scler1997，3(2):157．
[46] Cheng C, Zochodne DW. In vivo proliferation，migration and phenotypic changesof． Schwann cells in the prsents of myelinated fibers Neuroscience2002;115:321-329．
[47] Luke E. Role of the Schwann cell in diabetic neuropathy.International ofNeurobiology2002;50：293-312．
[48] Evans GR. Peripheral never injury.A review and approach to tissue andengineering conducts．Anat Rec2001;263:396-404．
[49] Rhona M, Kristian RJ, Angela B, et a1. Schwann cells as regulations of nervedevelopment．Physiol Paris2002;96:17-20321.
[50] Hirota H., Kiyama H., Kishimoto T. and Taga T. Accelerated nerve regeneration inmice by upregulated expression of interleukin(IL)6and IL-6receptor after trauma.Exp. Med1996;183:2627–2634.
[51] Burnett MG, Zager EL. Pathophysiology of peripheral nerve injury: a brief review.Neurosurg Focus2004;16(5):1-7.
[52] Brenner MJ, Moradzadeh A, Myckatyn TM, et al. Role of timing in assessment ofnerve regeneration. Microsurgery2008;28(4):265-272.
[53]孙明芳,胡韶楠,徐建光.神经导管修复周围神经的临床应用.国外医骨科学分册2005;26（6）:371-373.
[54] Silva SS. Novel genipin-cross-linked chitosan/silk sibroin sponges forcartilageengineeringstrategies[J].Biomacromolecules2008;9(10):764-2774.
[1]王正敏,陆书昌.现代耳鼻咽喉科学.第一版,北京人民军医出版社2001;570-572.
[2]侯熙德,主编.神经病学.第三版人民卫生出版社1996;76-77.
[3]奥托森著,吕国蔚等译.神经系统生理学人民卫生出版社1987;35-41.
[4] Mirskya R, Jessena KR, Brennana A,et al. Schwann cells as regulators ofnervedevelopment.Journal of physiology-Paris2002;96（1-2）:17-24.
[5] Burnett MG, Zager EL. Pathophysiology of peripheral nerve injury: a brief review[J].Neurosurg Focus2004;16(5):1-7.
[6] Dyck PJ, Thomas PK. Peripheral neuropathy.Philadelphia: W.B.Saunders Co1993;290一298.
[7] Torigoe K, Tanaka HF, Takahashi A, et al. Basic Behavior of Migratory SchwannCells in Peripheral Nerve Regeneration. Experimental neurology1996;137(2):301-308.
[8] Cheng C，Zochodne DW．In vivo proliferation，migration and phenotypic changesof Schwann cells in the prsents of myelinated fibers Neuroscience2002;115：321—329．
[9] Luke E． Role of the Schwann cell in diabetic neuropathy. International review ofNeurobiology2002;50:293-312．
[10] Evans GR. Peripheral never injury. A review and approach to tissue andengineering conducts． Anat Rec2001;263:396-404.
[11]陈菁,楚燕飞,顾玉东等．培养施旺细胞NGF、CNTF和GDNF共表达和共定位实验研究．中华手外科杂志2005;21:317-319.
[12]何继银,劳杰,蒋良福，等．激活态施旺细胞信号转导通路的初步研究.中华手外科杂志2006;22:376-378.
[13] Bünge RP. Expanding roles for the Schwann cell: ensheathment, myelination,trophism and regeneration. Curr. Opin. Neurobiol1993;3:805-809.
[14] Jessen KR, Mirsky R. Schwann cells and their precursors emerge as major regulatorsofnerve development. Trends Neurosci1999;22:402-410.
[15] Singer AJ, Clark RA. Cutaneous wound healing. N. Engl. Med1999;341:738-746.
[16] Sendtner M, Holtmann B, Kolbeck R, Thoenen H, Barde Y.A. Brain-derivedneurotrophic factor prevents the death of motoneurons in newborn rats after nervesection. Nature1992;360:757-759.
[17] Hoke A, Cheng C, Zochodne DW. Expression of glial cell line-derived neurotrophicfactor family of growth factors in peripheral nerve injury in rats. NeuroReport2000;11:1651-1654.
[18] Meyer M, Matsuoka I, Wetmore, C, Olson L, Thoenen H. Enhanced synthesisofbrain-derived neurotrophic factor in the lesioned peripheral nerve: differentmechanisms are responsible for the regulation of BDNF and NGF mRNA. J. Cell Biol1992;119:45-54.
[19] Herdegen T, Leah GD, Inducible and constitutive transcription factors in themammalian nervous system,control of gene expression by Gun,Fos and Krox andCREB/REF proteins. Brain Res.Rev1998;28:370-490.
[20] Molander C, Hongpaisan J, Shord and P. Avotapic redistribution of c-fos expressingneurons in the superficial dorsalhorll after peripherial nerve injury Neuroscience1998;84(1):24l.
[21] Wu W, Li L, Yick LW, et al. GDNF and BDNF alter expression of neuronalNOS,c-jun P75and prevent motoneuron death foll1wing spinal root avulsion in adultrats J.Neurotrauma2003;20(6):603-612.
[22] Herdegen T, Skene P,Bahr M. The c-jun transcription factor by Potential mediator ofneuronal death, survival and regeneration. Trends Neurosci1997;20:227-231.
[23] Dragunow M, Young D, Hughes P,et al. As c-jun involved in nerve cell deathfollowing status epilepticus and hypoxic-ischaemic brain injury?Brain Res. Mol1993;18:347-352.
[24] Anderson AJ, Cummings BJ, Cotman C.W.I ncreased immunoreactivity for Jun andFos-related proteins in Alzhemer’s disease,association with pathology. Exp neurol1994;125:286-295.
[25] Schaden H, Stuermer CA,Bahr M. GAP-43immunoreactivity and axon regenerationin retinal ganglion cells of the rat.J.Neurobiol1994;25:1570-1578.
[26] Robison GA. Axotomy-induced regulation of c-jun expression in regenerating ratretinal ganglion cells Brain Res. Mol1995;30:61-69.
[27] Raich G, Bohatschek M, Da Costa C,et al. The AP-1transcription factor c-jun isrequired for efficient axonal regeneration.Neuron2004;43:57-67.
[28] Fu SY, Gordon T. The cellular and molecular basis of peripherial nerve regeneration.Mol. Neurobiol1997;14:67－116.
[29] Ide, C. Peripheral nerve regeneration. Neurosci. Res，1996，25(2):101-121.
[30] Barde, YA. Trophic factors and neuronal survival.Neuron1989;2：1525－1534.
[31] Korsching,s. The neurotrophic factor concept a reexamination. Neurobiol1993;25:759-766.
[32] Korsching, S. The neurotrophic factor concept: a reexamination. Neurosci1993;13:2739-2748.
[33] Richardson, PM. Neurotrophic factors in regeneration. Curr. Opin. Neurobiol1991;1:401-406.
[34] Richardson, PM. Ciliary neurotrophic factor: a review. Pharmacol. Ther1994;63:187-198.
[35] Henderson CE, Philips HS, Pollock RA,et al. GDNF,a pertent survival factor formotoneurons present in peripherial nerve and muscle. Science1994;266:1062－1064.
[36] Trupp M, Ryden M, Jornvall H et al. peripherial expressions and biological activitiesof GDNF,a neurotrophic factor for avian and mammalian peripherial neurons. CellBiol1995;130:137－148.
[37] Golden GP,Baloh RH,Kotzbauer PT,et al Expression of neurturin,GDNF and theirreceptors in the adult mouse CNS. Comp. Neurol1998;398:139-150.
[38] Golden JP, Demaro JA,Osborne PA, et al. Exprssion of neurturin,GDNF and GDNFfamily-receptor mRNA in the developing and mature mouse.Exp. Neurol1999;158(2):504－528.
[39] Wilkins A, Majed H, Layfield R,et al. Oligodendrocytes promote neuronal survivaland axonal length by distinct intralcellular mechanisms,novel role forOligodendrocytes derived glial cell line-derived neurotrophic factor. Neuroscience2003;23:4967－4974.
[40] Airaksinen MS,Saarma M. The GDNF family,singalling biological functions andtherapeutic value. Nat. Rev,Neurosci2002;3:383－394.
[41] Bohn MC.Motoneurons crave glial cell line-derived neurotrophic factor.Exp. neurol2004;190:263－275.
[42] Alexander Parsadanian, Yanchun pan, Wen li, et al. Astrocyte-derived transgeneGDNF promotes complete and long-term surval of adult facial moto neuronsfollowing avulsion and diffentially regulates the expression of transcription factors ofAP-1and ATF/CREB families.Experimental neurology2006;200:26-37.
[43] Nicole O, Ali C,Docagne F, et al. Neuroprotection mediated by glial cell line-derivedneurotrophic factor,involvement of a reduction of NMDA-induced calcium infux bythe mitogen-activiated protein kinase passway. G. Neurosci2001;21(9):3024－3033.
[44] Zhao Z, Alam S, Oppenheim RW, et al. Overexpression of glial cell line-derivedneurotrophic factor in the CNS rescues motoneurons from programmed cell death andpromote their long_term survival following axotomy. Exp. Neurol2004;190:356－372.
[45] Sendtner M, Stuckli KA, Thoenen H. Synthesis and localization of ciliaryneurotrophic factor in the sciatic nerve of the adult rat after lesion and duringregeneration. Cellbiol1992;118:139-148.
[46] Dolcet X, Soler RM, Gould T.W, et al. Cytokins promote motoneuron survivalthrough the Janus kinase-dependant activation of the phosphatidylanositoll3-kinssepassway. Mol. Cell. Neurosci2001;18(6):619-631.
[47] Schwaiger FW, Hager G, Schmitt AB, et al. Periopherial but not central axotomyinduced changes in Janus kinse(JAK) and signal transducers and activiators oftranscription(STAT).Eur. Neurosci2000;12(4):1165-1176.
[48] Schwaiger U, Gunnersen J, Karch C.et al conditional gene ablation of STAT3reviwsdifferential signaling requirement for survival of motoneurons during developmentand after nerve injury in th adult. Cell Biol2002;156:287-297.
[49] Matthias K, Ulrich T, Hans-dieter H. Ciliary neurotrophic factor is an earlylesion-induced retrograde signal for axotomied facial motoneurons. Molecular andCellular Neuroscience2003;24:130-138.
[50] Hasas CA, Hofmann HD, Kirsh M. Expression of CNTF/LIF receptor componentand activation of STAT3singaling in axotomized facial motoneurons,evidents for asequential post lesional function of the cytokines. Neurobiol1999;41:559-571.
[51] Bregman BS, McATee M, Dai HN, et a1. Neurotrophic factors increase axonalgrowth after spinal cord injury and transplantation in the adult rat.Exp Neurol1997;148(2):475-494．
[52] Giehl KM,￡zla w. BDNF and NT一3, but not NGF，prevents axotomy induceddeath of rat corticospinal neurons in vivo[J]. Eur Neumsci1996;8(6):1167—1175．
[53] Narniki J, Kojima A, Tator CH. Effect of brain—derived neurotrophic factor, nervegrowt h factor, and neurotrophic3on functional recovery an dregeneration afterspinal cord injury in adult rats. Neurotrauma2000;17(12):1219—1231．
[54] Mertz K, Koscheckt T. Schilling. Brain gliaderiverd neurotrophic factor modulatesdendrite． morpholog of cerebella baskcet and stellate cells： An in vitrostudy．Neurosience2000;97(2):303.
[55] Ekberg J, Brunhof C, Jaras M, et a1．Increased expression of cyclin A1protein isassociated with all trans retinoic acid induced apoptosis J．1nt J Bioechem Cell Biol2006;38(8):1330-1339.
[56]李学礼,吕立夏,张红娟.脑源性神经营养因子在体外诱导SH--SY5Y细胞分化过程中的作.解剖学报2OO7;38（6）:688-681.
[57] Almeida RD. Maned as BJ, Me1o CV, et al. Neamprotection by BDNF againstglutamate induced apoptotic cell death is mediated by ERK and PI3一kinasepathways． Cell Death Diffe2005;12(10):1329-43.
[58] Hosnsin MA. Russel JC, Gomez R,et a1. Neuroprotection by scatterfactor hepatocytegrowth factor an d FGF-1in cerebellar granule neuron is phosphatidylinositol3-kinase／akt. dependent and MAPK CREB—independent. J Neurochem2001;81(2)：365-78.
[59] Madeddu F, Naska S. Bozzi Y．BDNF down-regulates the caspase3pathway ininjured geniculocortical neuron．Neuroreport2004;15(13):2045-9.
[60] Leeds P, LengY, Chalecka-Franszek E, et al. Neumtrophin protect a cytosinearabinoside-induced apoptosis of irnmature rat cerebelar neuron. Neurock2005;46(1):61—72.
[61]孙继虎,肖杭.脑源性神经营养子对海马神经元NMDA受体功能下调的逆转作用.中国神经科学杂志2000;16(4):349.
[62] Naff NJ, Ecklund JM. The History of Peripheral Nerve Surgery. Techniques.Neurosurg Clin N Am2001;12(1):197-209.
[63]王敏,杨志焕.周围神经损伤修复方法研究进展.创伤外科杂志2002;4（1）:51-54.
[64]赵建军,李泽山.面神经缺损修复与再生的研究进展.锦州医学院学报2000;21(5):51-53.
[65] Cueva RA, Robbins KT, Martin PJ. Lower cervical cutaneous sensory nerves:analternative for facial nerve3cable grafting [J].Otolaryngol Head Neck surg1996;114(3):479481.
[66]刘大庸,胡恨民,董敬朋.耳大神经移植体的应用解剖学.临床应用解剖学杂志1985;3(2):95-96.
[67]蒋常文,陆明深.耳大神经移植治疗面神经麻痹的应用解剖研究.解剖学杂志1995;18(6):502-503.
[68]钟世镇.临床应用解剖学.北京:人民军医出版社1995;764-790.
[69]廖进民,苗华,钟世镇.四肢皮神经营养血管筋膜皮瓣的应用解剖学研究回顾[J],中华国际医学杂志2002;2(4):353-356.
[70] Fansa H, Schneider W, Wolf O, et al. Host responses after acellular muscle basallamina allografting used as a matrix for tissue engineered nerve grafts.Transplantation2002;74(3):381-387.
[71]葛平江,高志强,曹克利等.微波变性自体骨骼肌和异体神经修复面神经缺损的实验研究.中华耳鼻咽喉科杂志2000;35(6):42-45.
[72]朱国臣,娄卫华,孙永强等.同种异体神经修复面神经缺损的实验研究.中国临床康复2004;8(11):2068-2069.
[73] Sondel M, Lundborg G, Kanje M. Regeneration of the rat sciatic nerve into allograftsmade scellular through chemical extraction. Brain Res1998;795(1-2):44-54.
[74] Borschel GH, Kis KF, Kuson WM Jr, et al. Mechanical properties of acellularperipheral nerve. Surg Res2003;114(2):133-139.
[75]刘世清,张思胜,彭昊等.化学萃取同种异体神经修复鼠坐骨神经缺损.武汉大学学报(医学版)2004;25(2):129-136.
[76] Seckel BR. Enhancement of peripheral nerve regeneration. Muscle Nerve1990;13:785-800.
[77]宋修竹,顾玉东,徐建光.不同对位情况下神经直接缝合与小间隙套管法修复的疗效比较.中华手外利杂志1998;14:250-251.
[78] Myers RR, Powell HC. Endoneurial fluid is hypertonic. Results of microanalysis andits aignificance in neuropathy. I Neuropath Exp Neurol1983;42:217-224.
[79] Ochi M, Ikuta Y, Miycamato Y, et al. Experimental evidence of selective axonalregeneration in allogenic and isogenic chambers. Exp Neurol1992;115:260.
[80] Willims LR. Rat aorta isografts possess nerve regeneration promoting properties insililone Y chambers. Exp Neurol1987;93:555.
[81] Wang KK, Costas PD, Bryan DJ, et al. Inside-out vein graft promotes improvednerve regeneration in rats. Microsurgery1993;14:608-618.
[82]陈书连,贺长清,吴学建.翻转静脉桥接修复周围神经缺损的实验研究.中华显微科科杂志1998;21:208-211.
[83] Meek MF, Coert JH. Clinical use of nerve conduits in peripheral nerve repair: reviewof literature. J Reconstr Microsurg2002;18:97-109.
[84] Jkema-Paassen J, Jansen K, Gramsbergen A, et al. Transection of peripheral nerves,bridging strategies and effect evaluation. Biomaterials2004;25(9):1583-1592.
[85] Battiston B, Tos P, Cushway TR, et al. Nerve repair by means of vein filled withmuscle graftsⅠ.Clinical results. Microsurgery2000;20(1):32-36.
[86] Brandt J, Dahlin LB, Kanje M, et al. Functional recovery in a tendon autograft usedto bridge a Peripheral nerve defect. Scand J Plast Surg Hand Surg2002;36(1):2-8.
[87]张琪,顾晓明,俞光岩等.复合许旺细胞的羊膜衍生物膜修复神经缺损的动物实验.中华口腔医学杂志2006;41(2):98-101.
[88]卫晓恩,韩西城.多种移植体修复周围神经的比较实验研究.中国修复重建外科杂志1996;10:12-15.
[89]卫晓恩,韩西城.多种移植体修复周围神经的比较实验研究.中国修复重建外科杂志1996;10:12-15.
[90] Lundborg G, Danielsen N. Ulnar nerve repair by the silicone chamber technique: casereport. Scand J Plast Reconstr Hand Surg1991;25:79-82.
[91] Braga SJ. The use of silicone tubing in the late repair of the median and ulnar nervesin the forearm. Hand Surg1999;24:703-706.
[92] Chen YS, Hsieh CL, Tsai CC, et al. Increased success of Peripheral nerveregeneration using silicone rubber chambers filled with collagen,laminin andfibronectin. Biomaterials2000;21:1541-1547.
[93] Kosaka M. Enhancement of rat peripheral-nerve regeneration through artery-including silicone tubing, Exp Neurol1990;107(1):69-77.
[94] Gibson KL, Paniloff JK. Comparison of sciatic nerve regeneration through siliconetube and nerve allograft[J]. Microsurgery1989;10:126-129.
[95] Pogrel MA, Mcdonald AR, Kaban LB. Gore-Tex tubing as a conduit for repair oflingual and inferior alveolar nerve continuity defects: a preliminary report[J]. J OrolMaxillofac Surg1998;56:319-321.
[96] Evans GR, Brandt Widmer MS, et al. In vivo evaluation of poly (L-lactic acid)porous conduits for peripheral nerve regeneration. Biomaterials1999;20:1109-1115.
[97] Hadlock T, Elisseef J, Langer R, Vacand J, Cheney M. A tissue-engineered conduitfor peripheral nerve repair. Arch Otolaryugol Head Neck Surg1998;124(l):1081-6.
[98] Molander H, Olsson Y, Engkvist O, et al. Regeneration of peripheral nerve through apolyglactin tube. Muscle Nerve1982;5:54.
[99] Robinson PH, Van der Lei B, Hoppen HJ, et al. Nerve regeneration through atwo-plybiodegradable nerve guide in the rat. Microsurgery1991;12:412.
[100]陈西广,刘万顺,刘晨光.几丁质的研究与进展.生物工程展1997，17:5-9.
[101]匡勇,侯春林,苟三怀,等.几丁质糖管修复周围神经缺损的实验研究.中华创伤杂志1998;14:72-74.
[102]匡勇,候春林,苟三怀，等.几丁质及几丁糖与施旺氏细胞相容性的实验研究.中国修复重建外科杂志1998;12:90-93.
[103] Luciano RM, de Carvalho Iavaglia CA, de Rerende Duek EA. Preparation ofbioabsorbable nerve guide tube. Artif Organs2000;24(3):206-208.
[104] Hoppen HJ, Leenslag JW, Pennings AJ, et al. Two-plybiodegradable nerve guide:basic aspects of design, construction and biological performance. Biomaterials1990;11:286-290.
[105] Mackinnon SE, Dellon AL. Clinical nerve reconstruction with a bioabsorbablepolyglycolic acid tube. Plast Reconstr Surg1990;85:419-424.
[106] Yannas IV, Hill BJ. Selection of biomaterials for peripheral nerve regeneration usingdata from the nerve chamber model. Biomaterials2004;25(9):1593-1600.
[107] Navissano, Malan F, Carnino R, et al. Neurotube for facial nerve repair[J].Microsurgery2005;25(4):268-271.
[108] Den Dunnen WF, Van der Lei B, Robinson PH, et a. Biological performance of adegradable poly (lacticacid-ε-caprolac-tone) nerve guide: influence of tubedimensions. J Biomed Mater Res1995;29(6):757-766.
[109] Sieminski AL, Gooch KJ. Biomaterial-microvaseulature interactions. Biomaterials2000;21:2233-2241.
[110]兰学文,杨志.组织工程化神经研究进展．医学综述2006;12(6):330-331.
[111] Burkhard B. Muller E, Schroder B, et a1. Rat Schwann cells in bioresorbable nerveguides to promote and accelarate axonal regeneration. Brain Res2003;963(1-2):321-328.
[112] Yamada H,Igarashi Y,Takasu Y,et al.Identifi cation of fi broin-derived peptidesenhancing the proliferation of cultured human skin fi broblasts.Biomaterials2004;25(3):467-472.
[113] Kim SH, Nam YS, Lee TS, et al. Silk Fibroin Nanofiber. Electrospinning, Properties,and Structure. Polymer Journal2003;35:185-190.
[114] Jin HJ, Park J, Valluzzi R, et al. Biomaterial films of B. mori silk fibroin withpoly(ethyleneoxide). Biomacromolecules2004;5(3):711–717.
[115] Li M, Ogiso M, Minoura N. Enzymatic degradation behavior of porous silk fibroinsheets. Biomaterias2003;24(2):357-365.
[116] Li D, Marquez M, Xia YN. Capturing electrified nanodroplets under Rayleighinstability by coupling electrospray with a sol-gel reaction. Chem Phys Lett2007;445:271-275.
[117] Marginean I, Nemes P, Vertes A. Order-Chaos-Order transitions in electrosprays: theelectrified dripping faucet. Phys Rev Lett2006;97(6):45-52.
[118] Deitzel JM, Kleinmeyer J, Harris D, et al. The effect of processing variables on themorphology of electrospun nanofibers and textiles. Polymer2001;42:261-272.
[119] Min BM,You Y,Kim JM,et al.Formation of nanostructured poly (lactic-co-glycolicacid)/chitin matrix and its cellular response to normal human keratinocytes andfibroblasts. Carbohydr Polym2004;57:285-292.
[120] Zhang F, JZ Qin, R Liu, BQ Zuo. Electrospun silk fibroin nanofiber tubes forperipheral nerve regeneration. ICBBE2010.
[121] Bini TB, Gao SJ, Tan TC, et al. Electrospun poly(L-lactide-co-glycolide)biodegradable polymer nanofiber tubes for peripheral nerve regeneration.Nanotechnology2004;15:1459-1464.
[122] Chew SY, Mi RF, Hoke A, et al. Aligned Protein-Polymer Composite Fibers EnhanceNerve Regeneration: A Potential Tissue-Engineering Platform. Adv Funct Mater2007;17(8):1288-1296.
[123] Yumin Yang, Xuemei Chen, Fei Ding,et al. Biocompatibility evaluation of silkfibroin with peripheralnerve tissues and cells in vitro. Biomaterials2007;28:1643–1652.
[124]吴坚,严小莉,赵亚红，等.人工神经移植物丝素蛋白导管的生物相容性的初步研究.组织工程与重建外科杂志2009;5(2):86-88.
[125]陆艳,迟放鲁,赵霞，等.丝素导管修复面神经缺损的实验研究.中华耳鼻咽喉头颈外科杂志2006;41(8):603-606.
[126]谭学新,马丽，李波，等.丝素-壳聚糖神经导管修复兔面神经缺损的神经电生理变化.中国医科大学学报2009;38（4）253-255.
[127] Yumin Yang, Fei Ding, Jian Wu,et al. Development and evaluation of silkfibroin-based nerve grafts used for peripheral nerve regeneration Biomaterials2007;28:5526–5535
[128] Meek MF, Coert JH. Clinical use of nerve conduits in peripheral-nerve repair:review of the literature. Reconstr Microsurg2002;18:97-109.
[2] Luke E. Role of the Schwann cell in diabetic neuropathy. International review ofNeurobiology2002;50:293-312.
[3] Evans GR. Peripheral never injury. A review and approach to tissue andengineering conducts. Anat Rec2001;263:396-404.
[4]陈菁,楚燕飞,顾玉东,等.培养施旺细胞NGF、CNTF和GDNF共表达和共定位实验研究.中华手外科杂志2005;21:317-319.
[5]何继银,劳杰,蒋良福,等.激活态施旺细胞信号转导通路的初步研究.中华手外科杂志2006;22:376-378.
[6] Rhona Mirskya, Kristjan R. Jessena, Angela Brennana,et al. Schwann cells asregulators of nerve development.Journal of physiology-Paris2002;(96):17-24.
[7] Burnett MG,Zager EL. Pathophysiology of peripheral nerve injury: a brief review[J].Neurosurg Focus2004;16(5):1-7.
[8] Bünge R.P. Expanding roles for the Schwann cell: ensheathment, myelination,trophism and regeneration. Curr. Opin. Neurobiol1993;3:805-809.
[9] Jessen K.R, Mirsky R. Schwann cells and their precursors emerge as majorregulators ofnerve development. Trends Neurosci1999;22:402-410.
[10] Singer A.J, Clark R.A. Cutaneous wound healing. N. Engl. J. Med1999;341:738-746.
[11] Sendtner M, Holtmann B, Kolbeck R, Thoenen H, Barde Y.A. Brain-derivedneurotrophic factor prevents the death of motoneurons in newborn rats after nervesection. Nature1992;360:757-759.
[12] Hoke A., Cheng C, Zochodne D.W. Expression of glial cell line-derivedneurotrophic factor family of growth factors in peripheral nerve injury in rats.NeuroReport2000;11:1651-1654.
[13] Meyer M, Matsuoka I, Wetmore C, Olson L, Thoenen H. Enhanced synthesisofbrain-derived neurotrophic factor in the lesioned peripheral nerve: differentmechanisms are responsible for the regulation of BDNF and NGF mRNA. J. Cell Biol1992;119:45-54.
[14]宋涛,伶晓杰.施旺细胞与周围神经再生.解剖科学进展2000;6(1):27-2.
[15] Daniel GO. Gila—neuron crosstalk in the neuroprotective mechanisms of sex steroidhormones.Brain Res Brain Res Rev2005;48:273-286.
[16] Cheng C, Qin YW, Shao XY,et al. Induction of TNF-a by LPS in Schwann Cellis Regulated by MAPK Activation Signals. Cell Mol Neurobiol2007;27:909–921.
[17] Cochan M.Schwann cell fail to differentiate when co-culture in contact with PC12neurites.Brain Res1985;351:89-93.
[18] Wood PM.Separation of functioned Schwann cells and neurons from normalperipheral nerve tissue.Brain Res1976;115:361-375.
[19] Brockes JP,Fields KL,Reff MC.Studies on cultured rat Schwann cells. Establishmentof purified population from cultures of peripheral nerve. Brain Res1979;165:105-118.
[20] Xu XM,Guenard V, Kleitman N. Axonal regeneration into Schwann cell-seededguidance channels grafted into transected adult rat spine cord.J Compara Neurol1995;351:145-160.
[21]连小峰,侯铁胜,傅强,等.植块法与酶消化法结合培养原代大鼠施旺细胞.中国脊柱脊髓杂志2008;18（9）:703-706.
[22]何晶,李锋,丁文龙.施旺氏细胞体外培养不同方法的比较.解剖学杂志2006;29（3）:384-386.
[23]黄小强,罗卓荆,李明全.新生SD大鼠坐骨神经施旺细胞培养与纯化的方法学研究.中华创伤骨科杂志2005;7（4）:341-343.
[24] Askanas V. Engel WK，Dalakas MC，et a1. Human schwann cells in tissue culture：histochemical and uhrastructural studies. J.Arch Neurol1980;37(6):329—337．
[25]洪坦辉,金羽青,戴传昌,等.复合胶原酶消化法制备高纯度小鼠雪旺细胞.组织工程与重建外科杂志2008;5(4):259-263.
[26]胡唏棠,熊良俭,劳杰.从成年大白鼠坐骨神经分离培养许旺细胞的方法学探讨.中华显微外科杂志2002;25(3):197-200.
[27] Kreider BQ, Messing A, Doan H.Enrichment of Schwanncell cultures from neonatalrat sciatic nerve by difIerential adhesion. Brain Res1981;207：433-449.
[28] Assouline JG, Bosch EP, Lim R. Purification of rat Schwann cells from cultures ofperipheral nerve: an immunoseleetive method using surfaces coatedantiimmunoglobun antibodies. Brain Res1983;227:389．
[29]孙晓红,窦文波,佟晓杰,等.许旺细胞与脱细胞神经移植物共培养在周围神经损伤修复中的作用.中国临床康复2006;29(10):19-21.
[30]朱伟,侍坚,路长林.新生大鼠雪旺细胞体外培养及纯化的方法比较.海军医学杂志2001;22(3):202-205.
[1] Burkhard S, Erhard M, Bernhard S, et al. Rat Schwann cells in bioresorbable nerveguides to promote and accelerate axonal regeneration. Brain Research2003;963:321-326.
[2] Christine E, Jennie B. Neural tissue engineering: Strategies for Repair andregeneration. Annu Rev Biomed Eng2003;5:293-347.
[3] Panseri S, Cunha C, Lowery J, Del Carro U, Taraballi F, Amadio S, et al.Electrospun micro-and nanofiber tubes for functional nervousregeneration in sciatic nerve transections. BMC Biotechnol2008;8:39.
[4] Cunha C, Panseri S, Antonini S．Emerging nanotechnology approaches in tissueengineering for peripheral nerve regeneration．Nanomedicine2011;(7):50–59.
[5] Yang YM, Chen XM, Ding F, et al. Biocompatibility evaluation of silk fibroin withperipheral nerve tissues and cells in vitro. Biomaterials2007;28:1643-1652.
[6] Chen XM, Yang YM, Wu J, et al. Biocompatibility studies of silk fibroin-basedartificial nerve grafts in vitro and in vivo. Prog Natur Sci2007;17(9):1029-1034.
[7] Yang YM, Wu J, Ding F, et al. Development and evaluation of silk fibroin-basednerve grafts used for peripheral nerve regeneration. Biomaterials2007;28:5526-5535.
[8]陆艳,迟放鲁,赵霞,等.丝素导管修复面神经缺损的实验研究.中华耳鼻咽喉头颈外科杂志2006;41（8）:603-606.
[9] Borys B, Sabine F, Charles J. K. et al. Functionality of endothelial cells on silkfibroin nets: Comparative study of micro-and nanometric fibre size. Biomaterials2008;29（5）:561-572.
[10] Ki CS, Park SY, Kim HJ, et al. Development of3-D nanofibrous fibroin scaffoldwith high porosity by electrospinning: implications for bone regeneration[J].Biotechnol Lett2008;30:405–410.
[11] Gupta D, Venugopal J, Prabhakaran MP, et al. Aligned and random nanofibroussubstrate for the in vitro culture of Schwann Cells for neural tissue engineering[J].Acta Biomaterialia2009;5(7):2560-2569.
[12] Martin CR. Membrane-based synthesis of nanomaterials. Chem Mater1996;8:1739-1746.
[13] Feng L, Li S, Li Y, et al. Super-hydrophobic surfaces: from natural to artificial. AdvMater2002;14(24):1857-1860.
[14] Fan YY, Cheng HM, Wei YL, et al. Tailoring the diameters of vapor-grown carbonnanofibers. Carbon2000;38:789-795.
[15] Ma PX, Zhang R. Microtubular architecture of biodegradable polymerscaffolds. J Biochem Mater Res Part A2001;56:469-77.
[16] Ondarcuhu T, Joachim C. Drawing a single nanofibre over hundreds of microns.Europhys Lett1998;42:215-220.
[17] Huang ZM, Zhang YZ, Kotaki M, et al. A review on polymer nanofibers byelectrospinning and their applications in nanocomposites[J]. Compos Sci Technol2003;63(15):2223-2253.
[18] Vleggeert-Lankamp CL, et al. Adhesion and proliferation of human Schwann cellson adhesive coatings. Biomaterials2004;25(14):2741–2751.
[19] Wang GL,Hu XD,Wei Lin et al. Electrospun PLGA–silk fibroin–collagennanofibrous scaffolds for nerve tissue engineering. Biol.—Animal2011;47:234–240.
[20] Ghasemi-Mobarakeh M, et al. Electrospun poly (3-caprolactone)/gelatinnanofibrous scaffolds for nerve tissue engineering.Biomaterials2008;29(34):4532–4539.
[21] Wang Y, Rudym DD, Walsh A, et al. In vivo degradation of threedimensional silkfibroin scaffolds. Biomaterials2008;29(24-25):3415-3428.
[22] Pham QP, Sharma U, Mikos AG. Electrospinning of polymeric nanofibers fortissue engineering applications: A review. Tissue Eng2006;12(5):1197-211.
[23] Lawrence BD, Marchant JK, Pindrus MA, et al. Silk film biomaterials for corneatissue engineering. Biomaterials2009;30(7):1299-1308.
[24] Murphy AR, St John P, Kaplan DL. Modification of silk fibroin using diazoniumcoupling chemistry and the effects on hMSC proliferation and differentiation.Biomaterials2008;29(19):2829-2838.
[25] Jin HJ, Chen J, Karageorgiou V, et al. Human bone marrow stromal cell responseson electrospun silk fibroin mats. Biomaterials2004;25(6):1039-1047.
[26] Wang X, Zhang X, Castellot J, et al. Controlled release from multilayer silkbiomaterial coatings to modulate vascular cell responses. Biomaterials2008;29(7):894-903.
[27] Zhang X, Baughman CB, Kaplan DL. In vitro evaluation of electrospun silk fibroinscaffolds for vascular cell growth. Biomaterials2008;29(14):2217-2227.
[28] Yang Y, Ding F, Wu J, et al. Development and evaluation of silk fibroin-basednerve grafts used for peri pheral nerve regeneration. Biomaterials2007;28(36):5526-5535.
[29] Zhang F, Qin JZ, Liu R, et al. Electrospun silk fibroin nanofiber tubes forperipheral nerve regeneration. ICBBE2010.
[30] Yim EKF, Leong KW. Significance of synthetic nanostructures in dictating cellularresponse. Nanomed Nanotechnol Biol Med2005;1:10–21.
[31] Chen CS, Mrksich M, Huang S, Whitesides GM, Ingber DE. Micropatternedsurfaces for control of cell shape, position and function. Biotechnology1998;14:356–63.
[32] Dalby MJ, Riehle MO, Yarwood SJ, Wilkinson CDW, Curtis ASG. Nucleusalignment and cell signaling in fibroblasts: response to a micro-groovedtopography.Exp Cell Res2003;284:274–82.
[33] Cunha C, Panseri S, Antonini S．Emerging nanotechnology approaches in tissueengineering for peripheral nerve regeneration．Nanomedicine2011;(7):50–59.
[34] Chew SY, Mi R, Hoke A, Leong KW. Aligned protein-polymer composite fibersenhance nerve regeneration: a potential tissue engineering platform. Adv Funct Mater2007;17:1288–96.
[35] Ogata T, Yamamoto SI, Nakamura K,Tanaka S. Signaling axis in Schwann cellproliferation and differentiation. Mol Neurobiol2006;33:51–61.
[36] Sing Yian Chew, Ruifa Mi, Ahmet Hoke. The effect of the alignment ofelectrospun fibrous scaffolds on Schwann cell maturation. Biomaterials2008;29:653–661.
[37] Yang F, Murugan R, Wang S, Ramakrishna S. Electrospinning of nano/micro scale poly(L-lactic acid) aligned fibers and their potential in neural tissueengineering. Biomaterials2005;26:2603-10.
[38] Klein R. Role of neurotrophins in mouse neuronal development. FASEB J1994;8(10):738–44.
[39] Yin Q, Kemp GJ, Frostick SP. Neurotrophins, neurones and peripheral nerveregeneration. J Hand Surg1998;23(4):433–7.
[40] Frostick SP, Yin Q, Kemp GJ. Schwann cells, neurotrophic factors and peripheralnerve regeneration. Microsurgery1998;18(7):397–405.
[41] Anand U, Otto WR, Casula MA, Day NC, Davis JB, Bountra C,et al. The effect ofneurotrophic factors on morphology, TRPV1expression and capsaicin responses ofcultured human DRG sensory neurons. Neurosci Lett2006;399(1–2):51–6.
[42] Moore K, MacSween M, Shoichet M. Immobilized concentration gradients Ofneurotrophic factors guide neurite outgrowth of primary neurons in Macroporousscaffolds. Tissue Eng2006;12(2):267–78.
[43] Hadlock T, Elisseeff J, Langer R, Vacanti J, Cheney M. A Tissueengineeredconduit for peripheral nerve repair. Arch Otolaryngol Head Neck Surg1998;124:1081–86.
[44]董运海，张锋，左保齐,等.再生丝素蛋白纳米纤维网支持和引导神经胶质细胞的生长与迁移.中国生物医学工程学报2009;28（1）:96-102，116.
[1] Cao H, Liu T, Chew SY. The application of nanofibrous scaffolds in neural tissueengineering. Adv Drug Deliv Rev2009;61(12):1055-64.
[2] Schmidt CE, Leach JB. Neural tissue engineering: strategies for repair andregeneration. Annu Rev Biomed2003;5:293–347.
[3] Schmidt CE, Shastri VR, Vacanti JP, et al. Stimulation of neurite outgrowth using anelectrically conducting polymer. Proc Natl Acad Sci1997;94:8948–8953.
[4] Beris A, Lykissas M, Korompilias A, Mitsionis G. End-to-side nerve repair inperipheral nerve injury. J Neurotrauma2007;24(5):909-16.
[5] Thomas F, Rivelino M, Hui SK, Molly SS. Chitin-based tubes for tissue engineeringin the nervous system. Biomaterials2005;26:4624–32.
[6] Wang X, Hu W, Cao Y, Yao J, Wu J, Gu X. Dog sciatic nerve regeneration across a30-mm defect bridged by a chitosan/PGA artificial nerve graft. Brain2005;128:1897–910.
[7] Bellamkonda RV. Peripheral nerve regeneration: an opinion on channels scaffoldsand anisotropy. Biomaterials2006;27:3515-8.
[8] Jiang BG, Yin XF, Zhang DY, Fu ZG, Zhang HB. Maximum number of collateralsdeveloped by one axon during peripheral nerve regeneration and the influence of thatnumber on reinnervation effects. Eur Neurol2007;58:12–20.
[9] Bini T.B, Gao Shujun, Wang Shu Ramakrishna S. Poly(l-lactide-co-glycolide)biodegradable microfibers and electrospun nanofibers for nerve tissue engineering: anin vitro study. Journal of Materials Science2006;41(19):6453-9）
[10] Huang YC, Huang YY. Tissue engineering for nerve repair. Biomed Eng ApplicBasis2006;18:100–110.
[11] Li C, Vepari C, Jin HJ, Kim HJ, Kaplan DL. Electrospun silk-BMP-2scaffolds forbone tissue engineering. Biomaterials2006;27(16):3115–24.
[12] Li J, He A, Zheng J, Han CC. Gelatin and gelatin-hyaluronic acid nanofibrousmembranes produced by electrospinning of their aqueoussolutions.Biomacromolecules2006;7(7):2243-7.
[13] Patel M, VandeVord PJ, Matthew HW, et al. Collagen-chitosan nerve guides forperipheral nerve repair: a histomorphometric study. J Biomater Appl2008;23(2):101-21.
[14] Gupta D, Venugopal J, Prabhakaran MP, Dev VR, Low S, Choon AT, Ramakrishna S.Aligned and random nanofibrous substrate for the in vitro culture of Schwann cellsfor neural tissue engineering. Acta Biomater2009;5(7):2560-9.
[15] Schnell E, Klinkhammer K, Balzer S, Brook G, Klee D, Dalton P, et al.Guidance ofglial cell migration and axonal growth on electrospun nanofibers ofpoly--caprolactone and a collagen/poly--caprolactone blend. Biomaterials2007;28:3012-25.
[16] Koh HS, Yong T, Chan CK, Ramakrishna S. Enhancement of neurite outgrowthusing nano-structured scaffolds coupled with laminin.Biomaterials2008;29:3574-82.
[17] Gelain F, Bottai D, Vescovi A, Zhang S. Designer self-assembling peptide nanofiberscaffolds for adult mouse neural stem cell3-dimensional cultures. PLoS ONE2006;e119:1.
[18] Cunha C, Panseri S, Antonini S．Emerging nanotechnology approaches in tissueengineering for peripheral nerve regeneration．Nanomedicine2011；(7):50–59.
[19] Yamada H, Igarashi Y, Takasu Y, et al. Identifi cation of fi broin-derived peptidesenhancing the proliferation of cultured human skin fi broblasts.Biomaterials2004;25(3):467-472.
[20] Kim SH, Nam YS, Lee TS, et al. Silk Fibroin Nanofiber. Electrospinning, Properties,and Structure. Polymer Journal2003;35:185-190.
[21] Li M, Ogiso M, Minoura N. Enzymatic degradation behavior of porous silk fibroinsheets. Biomaterias2003;24(2):357-365.
[22] Yang Y, Ding F, Wu J, Hu W, Liu W, Liu J, Gu X. Development and evaluation ofsilk fibroin-based nerve grafts used for peripheral nerve regeneration.Biomaterials2007;28(36):5526-35.
[23] Min BM, You Y, Kim JM, et al. Formation of nanostructured poly (lactic-co-glycolicacid)/chitin matrix and its cellular response to normal human keratinocytes andfibroblasts. Carbohydr Polym2004;57:285-292.
[24] Sill TJ, von Recum HA. Electrospinning: applications in drug delivery and tissueengineering. Biomaterials2008;29(13):1989-2006.
[25] Ashammakhi N, Wimpenny I, Nikkola L, Yang Y. Electrospinning: methods anddevelopment of biodegradable nanofibres for drug release. J Biomed Nanotechnol2009;5(1):1-19.
[26] Bechara SL, Judson A, Popat KC. Template synthesized poly(epsilon-caprolactone)nanowire surfaces for neural tissue engineering. Biomaterials2010;31(13):3492-501.
[27] Shahmoon A, Limon O, Girshevitz O, Zalevsky Z. Self assembly of nano metricmetallic particles for realization of photonic and electronic nano transistors.Int J MolSci2010;11(5):2241-52.
[28] Liu X, Ma PX. The nanofibrous architecture of poly(L-lactic acid)-based functionalcopolymers. Biomaterials2010;31(2):259-69.
[29] Ahmed J, Varshney SK, Auras R. Rheological and thermal properties ofpolylactide/silicate nanocomposites films. Food Sci2010;75(2):17-24.
[30] Kumbar SG, James R, Nukavarapu SP, Laurencin CT. Electrospun nanofiberscaffolds: engineering soft tissues. Biomed Mater2008;3(3):034002.
[31] Zhang YZ, Su B, Venugopal J, Ramakrishna S, Lim CT. Biomimetic and bioactivenanofibrous scaffolds from electrospun composite nanofibers. Int J Nanomedicine2007;2(4):623-38.
[32] Xu CY, Inaic R, Kotaki M. Aligned biodegradable nanofibrous structure: a potentialscaffold for blood vessel engineering. Biomaterials2004;25:877-886.
[33] Ju YW, Choi GR, Jung HR. Electrochemical properties of electrospun PAN/MWCNTcarbon nanofibers electrodes coated with polypyrrole. Electrochimica Acta2008;53(19):5796-5803.
[34] Shin MK, Kim YJ, Kim SI. Enhanced conductivity of aligned PANi/PEO/MWNTnanofbers by electrospinning. Sens Actuators B2008;134:122-126.
[35] Dalton PD, Klee D, Moller M. Electrospinning with dual collection rings. Polymer2005;46:611-614.
[36] Xin Yi, Huang Zonghao, Chen Jinfeng. Fabrication of well-aligned PPV/PVPnanofibers by electrospinning. Mater Lett，2008，62:991-993.
[37] Baker Brendon M., Mauck Robert L. The effect of nanofiber alignment on thematuration of engineered meniscus constructs. Biomaterials2007;28:1967-1977.
[38] Yu J, Qiu YJ, Zha XX, et al. Production of aligned helical polymer nanofbers byelectrospinning[J]. Eur Polym2008;44(9):2838-2844.
[39]周文,陈新,邵正中.红外和拉曼光谱用于对丝蛋白构象的研究[J].化学进展2006;18（11）:1514-1522.
[40] Hu AJ, Zuo BQ, Zhang F, Zhang HX, Lan Q. Biocompatibility evaluation ofelectrospun silk fibroin nanofibers with Schwann cells in vitro. Advanced MaterialsResearch2011;175-176:220-223.
[41] Wang Y, Kim HJ, Vunjak-Novakovic G, Kaplan DL. Stem cellbased tissueengineering with silk biomaterials. Biomaterials2006;August4,Epub ahead of print.
[42] Yang F, Murugan R., Ramakrishna S, Wang X, Ma YX, Wang S. Fabrication ofnano-structured porous PLLA scaffold intended for nerve tissue engineering.Biomaterials2004;25:1891-900.
[43] Wen X, Tresco PA. Effect of filament diameter and extracellular matrix moleculeprecoating on neurite outgrowth and Schwann cell behavior on multifilamententubulation bridging device in vitro. J Biomed Mater Res2006;76A:626–37.
[44] Dyck PJ, Thomas PK.Peripheralneuropathy.Philadelphia: W.B.Saunders Co1993;290-298.
[45] Baron-Van Evercooren A, Avellana-Adalid V, Lachapelle F, et a1. Schwann celltransplantation and myelin repair of the CNS[J]．Mult Scler1997，3(2):157．
[46] Cheng C, Zochodne DW. In vivo proliferation，migration and phenotypic changesof． Schwann cells in the prsents of myelinated fibers Neuroscience2002;115:321-329．
[47] Luke E. Role of the Schwann cell in diabetic neuropathy.International ofNeurobiology2002;50：293-312．
[48] Evans GR. Peripheral never injury.A review and approach to tissue andengineering conducts．Anat Rec2001;263:396-404．
[49] Rhona M, Kristian RJ, Angela B, et a1. Schwann cells as regulations of nervedevelopment．Physiol Paris2002;96:17-20321.
[50] Hirota H., Kiyama H., Kishimoto T. and Taga T. Accelerated nerve regeneration inmice by upregulated expression of interleukin(IL)6and IL-6receptor after trauma.Exp. Med1996;183:2627–2634.
[51] Burnett MG, Zager EL. Pathophysiology of peripheral nerve injury: a brief review.Neurosurg Focus2004;16(5):1-7.
[52] Brenner MJ, Moradzadeh A, Myckatyn TM, et al. Role of timing in assessment ofnerve regeneration. Microsurgery2008;28(4):265-272.
[53]孙明芳,胡韶楠,徐建光.神经导管修复周围神经的临床应用.国外医骨科学分册2005;26（6）:371-373.
[54] Silva SS. Novel genipin-cross-linked chitosan/silk sibroin sponges forcartilageengineeringstrategies[J].Biomacromolecules2008;9(10):764-2774.
[1]王正敏,陆书昌.现代耳鼻咽喉科学.第一版,北京人民军医出版社2001;570-572.
[2]侯熙德,主编.神经病学.第三版人民卫生出版社1996;76-77.
[3]奥托森著,吕国蔚等译.神经系统生理学人民卫生出版社1987;35-41.
[4] Mirskya R, Jessena KR, Brennana A,et al. Schwann cells as regulators ofnervedevelopment.Journal of physiology-Paris2002;96（1-2）:17-24.
[5] Burnett MG, Zager EL. Pathophysiology of peripheral nerve injury: a brief review[J].Neurosurg Focus2004;16(5):1-7.
[6] Dyck PJ, Thomas PK. Peripheral neuropathy.Philadelphia: W.B.Saunders Co1993;290一298.
[7] Torigoe K, Tanaka HF, Takahashi A, et al. Basic Behavior of Migratory SchwannCells in Peripheral Nerve Regeneration. Experimental neurology1996;137(2):301-308.
[8] Cheng C，Zochodne DW．In vivo proliferation，migration and phenotypic changesof Schwann cells in the prsents of myelinated fibers Neuroscience2002;115：321—329．
[9] Luke E． Role of the Schwann cell in diabetic neuropathy. International review ofNeurobiology2002;50:293-312．
[10] Evans GR. Peripheral never injury. A review and approach to tissue andengineering conducts． Anat Rec2001;263:396-404.
[11]陈菁,楚燕飞,顾玉东等．培养施旺细胞NGF、CNTF和GDNF共表达和共定位实验研究．中华手外科杂志2005;21:317-319.
[12]何继银,劳杰,蒋良福，等．激活态施旺细胞信号转导通路的初步研究.中华手外科杂志2006;22:376-378.
[13] Bünge RP. Expanding roles for the Schwann cell: ensheathment, myelination,trophism and regeneration. Curr. Opin. Neurobiol1993;3:805-809.
[14] Jessen KR, Mirsky R. Schwann cells and their precursors emerge as major regulatorsofnerve development. Trends Neurosci1999;22:402-410.
[15] Singer AJ, Clark RA. Cutaneous wound healing. N. Engl. Med1999;341:738-746.
[16] Sendtner M, Holtmann B, Kolbeck R, Thoenen H, Barde Y.A. Brain-derivedneurotrophic factor prevents the death of motoneurons in newborn rats after nervesection. Nature1992;360:757-759.
[17] Hoke A, Cheng C, Zochodne DW. Expression of glial cell line-derived neurotrophicfactor family of growth factors in peripheral nerve injury in rats. NeuroReport2000;11:1651-1654.
[18] Meyer M, Matsuoka I, Wetmore, C, Olson L, Thoenen H. Enhanced synthesisofbrain-derived neurotrophic factor in the lesioned peripheral nerve: differentmechanisms are responsible for the regulation of BDNF and NGF mRNA. J. Cell Biol1992;119:45-54.
[19] Herdegen T, Leah GD, Inducible and constitutive transcription factors in themammalian nervous system,control of gene expression by Gun,Fos and Krox andCREB/REF proteins. Brain Res.Rev1998;28:370-490.
[20] Molander C, Hongpaisan J, Shord and P. Avotapic redistribution of c-fos expressingneurons in the superficial dorsalhorll after peripherial nerve injury Neuroscience1998;84(1):24l.
[21] Wu W, Li L, Yick LW, et al. GDNF and BDNF alter expression of neuronalNOS,c-jun P75and prevent motoneuron death foll1wing spinal root avulsion in adultrats J.Neurotrauma2003;20(6):603-612.
[22] Herdegen T, Skene P,Bahr M. The c-jun transcription factor by Potential mediator ofneuronal death, survival and regeneration. Trends Neurosci1997;20:227-231.
[23] Dragunow M, Young D, Hughes P,et al. As c-jun involved in nerve cell deathfollowing status epilepticus and hypoxic-ischaemic brain injury?Brain Res. Mol1993;18:347-352.
[24] Anderson AJ, Cummings BJ, Cotman C.W.I ncreased immunoreactivity for Jun andFos-related proteins in Alzhemer’s disease,association with pathology. Exp neurol1994;125:286-295.
[25] Schaden H, Stuermer CA,Bahr M. GAP-43immunoreactivity and axon regenerationin retinal ganglion cells of the rat.J.Neurobiol1994;25:1570-1578.
[26] Robison GA. Axotomy-induced regulation of c-jun expression in regenerating ratretinal ganglion cells Brain Res. Mol1995;30:61-69.
[27] Raich G, Bohatschek M, Da Costa C,et al. The AP-1transcription factor c-jun isrequired for efficient axonal regeneration.Neuron2004;43:57-67.
[28] Fu SY, Gordon T. The cellular and molecular basis of peripherial nerve regeneration.Mol. Neurobiol1997;14:67－116.
[29] Ide, C. Peripheral nerve regeneration. Neurosci. Res，1996，25(2):101-121.
[30] Barde, YA. Trophic factors and neuronal survival.Neuron1989;2：1525－1534.
[31] Korsching,s. The neurotrophic factor concept a reexamination. Neurobiol1993;25:759-766.
[32] Korsching, S. The neurotrophic factor concept: a reexamination. Neurosci1993;13:2739-2748.
[33] Richardson, PM. Neurotrophic factors in regeneration. Curr. Opin. Neurobiol1991;1:401-406.
[34] Richardson, PM. Ciliary neurotrophic factor: a review. Pharmacol. Ther1994;63:187-198.
[35] Henderson CE, Philips HS, Pollock RA,et al. GDNF,a pertent survival factor formotoneurons present in peripherial nerve and muscle. Science1994;266:1062－1064.
[36] Trupp M, Ryden M, Jornvall H et al. peripherial expressions and biological activitiesof GDNF,a neurotrophic factor for avian and mammalian peripherial neurons. CellBiol1995;130:137－148.
[37] Golden GP,Baloh RH,Kotzbauer PT,et al Expression of neurturin,GDNF and theirreceptors in the adult mouse CNS. Comp. Neurol1998;398:139-150.
[38] Golden JP, Demaro JA,Osborne PA, et al. Exprssion of neurturin,GDNF and GDNFfamily-receptor mRNA in the developing and mature mouse.Exp. Neurol1999;158(2):504－528.
[39] Wilkins A, Majed H, Layfield R,et al. Oligodendrocytes promote neuronal survivaland axonal length by distinct intralcellular mechanisms,novel role forOligodendrocytes derived glial cell line-derived neurotrophic factor. Neuroscience2003;23:4967－4974.
[40] Airaksinen MS,Saarma M. The GDNF family,singalling biological functions andtherapeutic value. Nat. Rev,Neurosci2002;3:383－394.
[41] Bohn MC.Motoneurons crave glial cell line-derived neurotrophic factor.Exp. neurol2004;190:263－275.
[42] Alexander Parsadanian, Yanchun pan, Wen li, et al. Astrocyte-derived transgeneGDNF promotes complete and long-term surval of adult facial moto neuronsfollowing avulsion and diffentially regulates the expression of transcription factors ofAP-1and ATF/CREB families.Experimental neurology2006;200:26-37.
[43] Nicole O, Ali C,Docagne F, et al. Neuroprotection mediated by glial cell line-derivedneurotrophic factor,involvement of a reduction of NMDA-induced calcium infux bythe mitogen-activiated protein kinase passway. G. Neurosci2001;21(9):3024－3033.
[44] Zhao Z, Alam S, Oppenheim RW, et al. Overexpression of glial cell line-derivedneurotrophic factor in the CNS rescues motoneurons from programmed cell death andpromote their long_term survival following axotomy. Exp. Neurol2004;190:356－372.
[45] Sendtner M, Stuckli KA, Thoenen H. Synthesis and localization of ciliaryneurotrophic factor in the sciatic nerve of the adult rat after lesion and duringregeneration. Cellbiol1992;118:139-148.
[46] Dolcet X, Soler RM, Gould T.W, et al. Cytokins promote motoneuron survivalthrough the Janus kinase-dependant activation of the phosphatidylanositoll3-kinssepassway. Mol. Cell. Neurosci2001;18(6):619-631.
[47] Schwaiger FW, Hager G, Schmitt AB, et al. Periopherial but not central axotomyinduced changes in Janus kinse(JAK) and signal transducers and activiators oftranscription(STAT).Eur. Neurosci2000;12(4):1165-1176.
[48] Schwaiger U, Gunnersen J, Karch C.et al conditional gene ablation of STAT3reviwsdifferential signaling requirement for survival of motoneurons during developmentand after nerve injury in th adult. Cell Biol2002;156:287-297.
[49] Matthias K, Ulrich T, Hans-dieter H. Ciliary neurotrophic factor is an earlylesion-induced retrograde signal for axotomied facial motoneurons. Molecular andCellular Neuroscience2003;24:130-138.
[50] Hasas CA, Hofmann HD, Kirsh M. Expression of CNTF/LIF receptor componentand activation of STAT3singaling in axotomized facial motoneurons,evidents for asequential post lesional function of the cytokines. Neurobiol1999;41:559-571.
[51] Bregman BS, McATee M, Dai HN, et a1. Neurotrophic factors increase axonalgrowth after spinal cord injury and transplantation in the adult rat.Exp Neurol1997;148(2):475-494．
[52] Giehl KM,￡zla w. BDNF and NT一3, but not NGF，prevents axotomy induceddeath of rat corticospinal neurons in vivo[J]. Eur Neumsci1996;8(6):1167—1175．
[53] Narniki J, Kojima A, Tator CH. Effect of brain—derived neurotrophic factor, nervegrowt h factor, and neurotrophic3on functional recovery an dregeneration afterspinal cord injury in adult rats. Neurotrauma2000;17(12):1219—1231．
[54] Mertz K, Koscheckt T. Schilling. Brain gliaderiverd neurotrophic factor modulatesdendrite． morpholog of cerebella baskcet and stellate cells： An in vitrostudy．Neurosience2000;97(2):303.
[55] Ekberg J, Brunhof C, Jaras M, et a1．Increased expression of cyclin A1protein isassociated with all trans retinoic acid induced apoptosis J．1nt J Bioechem Cell Biol2006;38(8):1330-1339.
[56]李学礼,吕立夏,张红娟.脑源性神经营养因子在体外诱导SH--SY5Y细胞分化过程中的作.解剖学报2OO7;38（6）:688-681.
[57] Almeida RD. Maned as BJ, Me1o CV, et al. Neamprotection by BDNF againstglutamate induced apoptotic cell death is mediated by ERK and PI3一kinasepathways． Cell Death Diffe2005;12(10):1329-43.
[58] Hosnsin MA. Russel JC, Gomez R,et a1. Neuroprotection by scatterfactor hepatocytegrowth factor an d FGF-1in cerebellar granule neuron is phosphatidylinositol3-kinase／akt. dependent and MAPK CREB—independent. J Neurochem2001;81(2)：365-78.
[59] Madeddu F, Naska S. Bozzi Y．BDNF down-regulates the caspase3pathway ininjured geniculocortical neuron．Neuroreport2004;15(13):2045-9.
[60] Leeds P, LengY, Chalecka-Franszek E, et al. Neumtrophin protect a cytosinearabinoside-induced apoptosis of irnmature rat cerebelar neuron. Neurock2005;46(1):61—72.
[61]孙继虎,肖杭.脑源性神经营养子对海马神经元NMDA受体功能下调的逆转作用.中国神经科学杂志2000;16(4):349.
[62] Naff NJ, Ecklund JM. The History of Peripheral Nerve Surgery. Techniques.Neurosurg Clin N Am2001;12(1):197-209.
[63]王敏,杨志焕.周围神经损伤修复方法研究进展.创伤外科杂志2002;4（1）:51-54.
[64]赵建军,李泽山.面神经缺损修复与再生的研究进展.锦州医学院学报2000;21(5):51-53.
[65] Cueva RA, Robbins KT, Martin PJ. Lower cervical cutaneous sensory nerves:analternative for facial nerve3cable grafting [J].Otolaryngol Head Neck surg1996;114(3):479481.
[66]刘大庸,胡恨民,董敬朋.耳大神经移植体的应用解剖学.临床应用解剖学杂志1985;3(2):95-96.
[67]蒋常文,陆明深.耳大神经移植治疗面神经麻痹的应用解剖研究.解剖学杂志1995;18(6):502-503.
[68]钟世镇.临床应用解剖学.北京:人民军医出版社1995;764-790.
[69]廖进民,苗华,钟世镇.四肢皮神经营养血管筋膜皮瓣的应用解剖学研究回顾[J],中华国际医学杂志2002;2(4):353-356.
[70] Fansa H, Schneider W, Wolf O, et al. Host responses after acellular muscle basallamina allografting used as a matrix for tissue engineered nerve grafts.Transplantation2002;74(3):381-387.
[71]葛平江,高志强,曹克利等.微波变性自体骨骼肌和异体神经修复面神经缺损的实验研究.中华耳鼻咽喉科杂志2000;35(6):42-45.
[72]朱国臣,娄卫华,孙永强等.同种异体神经修复面神经缺损的实验研究.中国临床康复2004;8(11):2068-2069.
[73] Sondel M, Lundborg G, Kanje M. Regeneration of the rat sciatic nerve into allograftsmade scellular through chemical extraction. Brain Res1998;795(1-2):44-54.
[74] Borschel GH, Kis KF, Kuson WM Jr, et al. Mechanical properties of acellularperipheral nerve. Surg Res2003;114(2):133-139.
[75]刘世清,张思胜,彭昊等.化学萃取同种异体神经修复鼠坐骨神经缺损.武汉大学学报(医学版)2004;25(2):129-136.
[76] Seckel BR. Enhancement of peripheral nerve regeneration. Muscle Nerve1990;13:785-800.
[77]宋修竹,顾玉东,徐建光.不同对位情况下神经直接缝合与小间隙套管法修复的疗效比较.中华手外利杂志1998;14:250-251.
[78] Myers RR, Powell HC. Endoneurial fluid is hypertonic. Results of microanalysis andits aignificance in neuropathy. I Neuropath Exp Neurol1983;42:217-224.
[79] Ochi M, Ikuta Y, Miycamato Y, et al. Experimental evidence of selective axonalregeneration in allogenic and isogenic chambers. Exp Neurol1992;115:260.
[80] Willims LR. Rat aorta isografts possess nerve regeneration promoting properties insililone Y chambers. Exp Neurol1987;93:555.
[81] Wang KK, Costas PD, Bryan DJ, et al. Inside-out vein graft promotes improvednerve regeneration in rats. Microsurgery1993;14:608-618.
[82]陈书连,贺长清,吴学建.翻转静脉桥接修复周围神经缺损的实验研究.中华显微科科杂志1998;21:208-211.
[83] Meek MF, Coert JH. Clinical use of nerve conduits in peripheral nerve repair: reviewof literature. J Reconstr Microsurg2002;18:97-109.
[84] Jkema-Paassen J, Jansen K, Gramsbergen A, et al. Transection of peripheral nerves,bridging strategies and effect evaluation. Biomaterials2004;25(9):1583-1592.
[85] Battiston B, Tos P, Cushway TR, et al. Nerve repair by means of vein filled withmuscle graftsⅠ.Clinical results. Microsurgery2000;20(1):32-36.
[86] Brandt J, Dahlin LB, Kanje M, et al. Functional recovery in a tendon autograft usedto bridge a Peripheral nerve defect. Scand J Plast Surg Hand Surg2002;36(1):2-8.
[87]张琪,顾晓明,俞光岩等.复合许旺细胞的羊膜衍生物膜修复神经缺损的动物实验.中华口腔医学杂志2006;41(2):98-101.
[88]卫晓恩,韩西城.多种移植体修复周围神经的比较实验研究.中国修复重建外科杂志1996;10:12-15.
[89]卫晓恩,韩西城.多种移植体修复周围神经的比较实验研究.中国修复重建外科杂志1996;10:12-15.
[90] Lundborg G, Danielsen N. Ulnar nerve repair by the silicone chamber technique: casereport. Scand J Plast Reconstr Hand Surg1991;25:79-82.
[91] Braga SJ. The use of silicone tubing in the late repair of the median and ulnar nervesin the forearm. Hand Surg1999;24:703-706.
[92] Chen YS, Hsieh CL, Tsai CC, et al. Increased success of Peripheral nerveregeneration using silicone rubber chambers filled with collagen,laminin andfibronectin. Biomaterials2000;21:1541-1547.
[93] Kosaka M. Enhancement of rat peripheral-nerve regeneration through artery-including silicone tubing, Exp Neurol1990;107(1):69-77.
[94] Gibson KL, Paniloff JK. Comparison of sciatic nerve regeneration through siliconetube and nerve allograft[J]. Microsurgery1989;10:126-129.
[95] Pogrel MA, Mcdonald AR, Kaban LB. Gore-Tex tubing as a conduit for repair oflingual and inferior alveolar nerve continuity defects: a preliminary report[J]. J OrolMaxillofac Surg1998;56:319-321.
[96] Evans GR, Brandt Widmer MS, et al. In vivo evaluation of poly (L-lactic acid)porous conduits for peripheral nerve regeneration. Biomaterials1999;20:1109-1115.
[97] Hadlock T, Elisseef J, Langer R, Vacand J, Cheney M. A tissue-engineered conduitfor peripheral nerve repair. Arch Otolaryugol Head Neck Surg1998;124(l):1081-6.
[98] Molander H, Olsson Y, Engkvist O, et al. Regeneration of peripheral nerve through apolyglactin tube. Muscle Nerve1982;5:54.
[99] Robinson PH, Van der Lei B, Hoppen HJ, et al. Nerve regeneration through atwo-plybiodegradable nerve guide in the rat. Microsurgery1991;12:412.
[100]陈西广,刘万顺,刘晨光.几丁质的研究与进展.生物工程展1997，17:5-9.
[101]匡勇,侯春林,苟三怀,等.几丁质糖管修复周围神经缺损的实验研究.中华创伤杂志1998;14:72-74.
[102]匡勇,候春林,苟三怀，等.几丁质及几丁糖与施旺氏细胞相容性的实验研究.中国修复重建外科杂志1998;12:90-93.
[103] Luciano RM, de Carvalho Iavaglia CA, de Rerende Duek EA. Preparation ofbioabsorbable nerve guide tube. Artif Organs2000;24(3):206-208.
[104] Hoppen HJ, Leenslag JW, Pennings AJ, et al. Two-plybiodegradable nerve guide:basic aspects of design, construction and biological performance. Biomaterials1990;11:286-290.
[105] Mackinnon SE, Dellon AL. Clinical nerve reconstruction with a bioabsorbablepolyglycolic acid tube. Plast Reconstr Surg1990;85:419-424.
[106] Yannas IV, Hill BJ. Selection of biomaterials for peripheral nerve regeneration usingdata from the nerve chamber model. Biomaterials2004;25(9):1593-1600.
[107] Navissano, Malan F, Carnino R, et al. Neurotube for facial nerve repair[J].Microsurgery2005;25(4):268-271.
[108] Den Dunnen WF, Van der Lei B, Robinson PH, et a. Biological performance of adegradable poly (lacticacid-ε-caprolac-tone) nerve guide: influence of tubedimensions. J Biomed Mater Res1995;29(6):757-766.
[109] Sieminski AL, Gooch KJ. Biomaterial-microvaseulature interactions. Biomaterials2000;21:2233-2241.
[110]兰学文,杨志.组织工程化神经研究进展．医学综述2006;12(6):330-331.
[111] Burkhard B. Muller E, Schroder B, et a1. Rat Schwann cells in bioresorbable nerveguides to promote and accelarate axonal regeneration. Brain Res2003;963(1-2):321-328.
[112] Yamada H,Igarashi Y,Takasu Y,et al.Identifi cation of fi broin-derived peptidesenhancing the proliferation of cultured human skin fi broblasts.Biomaterials2004;25(3):467-472.
[113] Kim SH, Nam YS, Lee TS, et al. Silk Fibroin Nanofiber. Electrospinning, Properties,and Structure. Polymer Journal2003;35:185-190.
[114] Jin HJ, Park J, Valluzzi R, et al. Biomaterial films of B. mori silk fibroin withpoly(ethyleneoxide). Biomacromolecules2004;5(3):711–717.
[115] Li M, Ogiso M, Minoura N. Enzymatic degradation behavior of porous silk fibroinsheets. Biomaterias2003;24(2):357-365.
[116] Li D, Marquez M, Xia YN. Capturing electrified nanodroplets under Rayleighinstability by coupling electrospray with a sol-gel reaction. Chem Phys Lett2007;445:271-275.
[117] Marginean I, Nemes P, Vertes A. Order-Chaos-Order transitions in electrosprays: theelectrified dripping faucet. Phys Rev Lett2006;97(6):45-52.
[118] Deitzel JM, Kleinmeyer J, Harris D, et al. The effect of processing variables on themorphology of electrospun nanofibers and textiles. Polymer2001;42:261-272.
[119] Min BM,You Y,Kim JM,et al.Formation of nanostructured poly (lactic-co-glycolicacid)/chitin matrix and its cellular response to normal human keratinocytes andfibroblasts. Carbohydr Polym2004;57:285-292.
[120] Zhang F, JZ Qin, R Liu, BQ Zuo. Electrospun silk fibroin nanofiber tubes forperipheral nerve regeneration. ICBBE2010.
[121] Bini TB, Gao SJ, Tan TC, et al. Electrospun poly(L-lactide-co-glycolide)biodegradable polymer nanofiber tubes for peripheral nerve regeneration.Nanotechnology2004;15:1459-1464.
[122] Chew SY, Mi RF, Hoke A, et al. Aligned Protein-Polymer Composite Fibers EnhanceNerve Regeneration: A Potential Tissue-Engineering Platform. Adv Funct Mater2007;17(8):1288-1296.
[123] Yumin Yang, Xuemei Chen, Fei Ding,et al. Biocompatibility evaluation of silkfibroin with peripheralnerve tissues and cells in vitro. Biomaterials2007;28:1643–1652.
[124]吴坚,严小莉,赵亚红，等.人工神经移植物丝素蛋白导管的生物相容性的初步研究.组织工程与重建外科杂志2009;5(2):86-88.
[125]陆艳,迟放鲁,赵霞，等.丝素导管修复面神经缺损的实验研究.中华耳鼻咽喉头颈外科杂志2006;41(8):603-606.
[126]谭学新,马丽，李波，等.丝素-壳聚糖神经导管修复兔面神经缺损的神经电生理变化.中国医科大学学报2009;38（4）253-255.
[127] Yumin Yang, Fei Ding, Jian Wu,et al. Development and evaluation of silkfibroin-based nerve grafts used for peripheral nerve regeneration Biomaterials2007;28:5526–5535
[128] Meek MF, Coert JH. Clinical use of nerve conduits in peripheral-nerve repair:review of the literature. Reconstr Microsurg2002;18:97-109.