提高化学去细胞异体神经再生速度和修复长度的实验研究
|
摘要
研究背景
周围神经损伤是临床上的难题,目前依然以自体神经移植修复为主要手段,但由于自体神经来源有限且供区有较多并发症,故多年来医学界不断寻找能替代自体神经移植的生物材料。在众多的替代材料中,去细胞异体神经显示了良好的应用前景。化学法萃取去细胞异体神经(Chemically ExtractedAcellular Nerve,CEAN),在最大限度地去除免疫原性物质的同时,较好地保存神经内部结构和细胞外基质的活性成分,成为修复周围神经缺损理想材料之一。
在我们前期的研究中,已经采用CEAN成功地修复了犬、猴的大段周围神经缺损,取得了良好效果,其有效修复长度范围可达8厘米。应用CEAN桥接周围神经损伤伤后,在再生神经纤维长入靶器官之前,患侧肌肉已发生严重萎缩,提高神经纤维再生速度,减轻肌肉萎缩对修复神经功能至关重要。此外,随着周围神经缺损长度的增加,神经修复效果降低,如何增加移植神经修复长度,已成为周围神经损伤研究重点之一。
相关的研究发现,CEAN中存在有利于神经生长的成分,也有不利于神经再生的成分,将这些抑制神经再生的物质去除,并保留促神经再生的物质,将进一步提高CEAN修复周围神经缺损效果。
研究目的
1对大鼠CEAN蛋白成分进行电泳分析,了解CEAN中免疫原性蛋白残存情况;在CEAN切片上,接种背根神经节,观察CEAN结构对神经再生的影响。
2为CEAN修复周围神经缺损补充缓释的外源性神经生长因子,观察该方法对神经再生生长速度、肌肉萎缩、神经组织再生情况的影响。
3应用软骨素酶ABC去除CEAN中不利于神经再生的物质-硫酸软骨素蛋白多糖(Chondroitin Sulfate Proteoglycan,CSPG),修复大鼠坐骨神经长距离缺损,评价去除CSPG对修复缺损距离的影响。
研究方法
第一部分CEAN蛋白成分及结构特性
按Sondell法制备大鼠的CEAN,将制备好的CEAN进行电泳分析,观察28-30 kDa区域的髓鞘蛋白的残留情况;将CEAN进行冰冻切片,接种鸡胚背根神经节,进行神经纤维荧光染色,观察神经纤维在CEAN切片上的生长方向。
第二部分神经生长因子(NGF)复合缓释制剂对提高CEAN修复周围神经缺损的实验研究
采用复乳溶媒蒸发—萃取法,以聚乳酸羟基/乙酸共聚物为材料制备NGF微球,与纤维蛋白胶混合制备成补充外源性NGF复合缓释制剂。体外进行NGF复合缓剂药物释放曲线,与鸡胚背根神经节共培养鉴定释放NGF的活性。体内实验,以桥接大鼠坐骨神经10mm缺损为模型,分为自体神经移植组(A组),CEAN+NGF复合缓释制剂组(B组);CEAN移植组(C组):CEAN移植+纤维蛋白胶组(D组),术后两周测量神经再生生长距离,术后4个月进行神经电生理、腓肠肌湿重、计算机图像分析等方面评价神经移植后的再生效果。
第三部分去除CEAN中的CSPG对修复周围神经缺损的实验研究
CEAN经软骨素酶ABC降解CSPG后,进行免疫组化染色,观察CSPG去除效果和对去细胞异体神经其它成分的影响。经软骨素酶ABC处理后的CSPG修复周围神经缺损为实验组(A组),桥接大鼠20mm周围神经缺损,对照组不作处理(B组),术后3个月,评价其修复周围神经效果。
研究结果
第一部分:CEAN电泳结果显示:28-30kDa区域髓鞘蛋白完全消失,化学萃取的去细胞神经可以完全去除髓鞘蛋白;背根神经节发出大量的神经纤维沿着CEAN基底膜管方向生长;而CEAN切片外侧仅有少量神经纤维生长。
第二部分:体外实验证明,NGF复合缓释制剂可持续释放NGF达60天以上,释出的NGF可促进鸡胚背根神经节神经纤维突起生长,具有较强的生物学活性。术后2周A组神经再生距离比其他组长(P＜0.05),B组优于C和D组(P＜0.05);C、D组间无差异无统计学意义(P＜0.05)。术后16周,A、B、C及D组小腿三头肌收缩力恢复率分别为85.33%±5.59%、69.79%±5.31%、64.46%±8.49%、63.35%±6.40%;A组优于其他3组(P＜0.05),B、C、D组间差异无统计学意义(P＜0.05)。A、B、C及D组肌肉湿重恢复率分别为62.54%±8.25%、53.73%±4.56%、46.37%±5.68%、45.78%±7.14%;A组三头肌湿重恢复率好于其他3组(P＜0.05),B组好于C和D组(P＜0.05);C、D组间无差异无统计学意义(P＜0.05)。组织学图像分析结果为B组在有髓神经纤维数量,轴突直径,髓鞘厚度,均优于C、D组(P＜0.05),轴突直径小于与A组(P＜0.05)。
第三部分:CSPG免疫组化染色结果显示,软骨素酶ABC可以明显去除CSPG,并保留促神经生长的Laminin有效成分。动物实验结果显示,术后2个月,两组都出现残足情况,A组仅一只大鼠出现残足,而B组6只大鼠出现残足。据Wall自残标准评分,两组进行等级资料秩和检验,P＜0.05,两者之间具有统计学差异。术后3个月,A组6只大鼠5只出现钳夹痛觉试验阳性,而B组仅1只大鼠出现阳性反应。进行四格表卡方检验,x~2=4.42,P＜0.05。两组之间具有显著性差异。在小腿三头肌肌张力恢复率和小腿三头肌肌湿重方面,两组比较,A组均优于B组。进行近端与远端吻合口HE染色A组神经纤维结构优于B组。
结论
1 CEAN中无残留引起免疫反应的髓鞘蛋白,保留的基底膜管结构对促神经纤维再生具有引导性作用。
2 NGF复合缓释制剂可以保护NGF活性,可以提高CEAN修复周围神经缺损的神经再生速度。
3软骨素酶ABC可以去除CEAN中CSPG,经软骨素酶ABC处理的CEAN可以增加修复周围神经缺损的长度。
Background:The treatment of peripheral nerve injury is a tough problem clinically. The standard clinical approach for bridging nerve defects is an autologous nerve graft, or autograft.Disadvantages of the autograft include limitation of the source of autologous nerve and loss of function at the donor site.Therefore,many researchs are focused on developing proper biomaterials as an alternate to autograft.Chemically extracted acellular nerve allograft(CEAN) which removes immunogenicity such as Schwann cells and myelin while restoring the nerve structures such as basal lamina tubes and extracellular matrix,is a promising material alternative to autograft.In nerve grafting,muscles may show irreversible atrophy and lose function before axonal regeneration into the distal targets.For CEAN,the speed of recovery of nerves regeneration must be increased and muscle atrophy decreased.In addition,the results of repiring the peripheral nerve defect with CEAN became worse while the length of peripheral nerve defect increasing.It becomes an important research subject that how to increase the length of repairing peripheral nerve defect.
Objective:
1.Electrophoretic analysis of rat CEAN protein is to be performed to know about the protein of CEAN.Dorsal root ganglia of chicken are cultured onto the surface of CEAN slice in order to observe the effect of CEAN structure on the fiber regeneration.
2.Sustained of nerve growth factor is to be deliveried for CEAN,used to repair injured nerves,to evaluate effect of the method on the speed of nerve regeneration, muscular atrophy and nerve tissue regeneration.
3.The protein of Chondroitin Sulfate Proteoglycan(CSPG) in CEAN is to be degraded by Chondroitin enzyme ABC,and the peripheral nerve large defects is to be repaired with these CEAN in order to evaluate the effect of degrading Chondroitin sulfate proteoglycan of CEAN on the length of repairing nerve defects. Methods:
ⅠThe protein and structure characteristics of CEAN The CEAN were perpared according to Sondell method and electrophoresed to observed whether the electrophoresis strip of 28-30kDa(Myelin Protein) exited or not.Dorsal root ganglia of chicken was cultured onto the surface of CEAN slice and dyed with nerve fiber fluorescence to observe the orientation of nerve fiber growth on the surface of CEAN slice.
ⅡExperiment on the effect of controlled nerve growth factor on peripheral nerve defect repaired by CEAN
The microspheres of NGF were prepared drug microsphere technology and fixed with the fibrin gels to make the complicated controlled release NGF.The Wister rats were randomly divided into four groups:Autograft group(A group),acellular nerve allograft+the double controlled release NGF(B group),acellular nerve allograft(C group) and acellular nerve allograft+fibrin glue(D group).The nerve regeneration length was measured 2 weeks after operation.The effects of peripheral nerve regeneration were evaluated by neural electrophysiology,the recovery rate of triceps surae muscular tension and weight and histological assessment 4 monthes after operation.
ⅢEffect of CSPG degraded by Chondroitin enzyme ABC in CEAN on repairing peripheral nerve defect
CEAN of which chondroitin sulfate proteoglycan was degraded by chondroitin enzyme ABC was immunohistochemistrily dyed with anti-CSPG in order to observe the remain of chondroitin sulfate proteoglycan and the other elements in CEAN.The Wister rats which left sciatic nerve was cut for 20 mm defect were randomly divided into two groups:CEAN degraded by chondroitin enzyme ABC(A group),CEAN(B group).The result of nerve regeneration was evaluated 3 monthes after operation.
Results:
ⅠElectrophoretic analysis of rat CEAN protein showed that the electrophoresis strip of 28-30kDa was totally disappeared.The large number of nerve fibers growed from DRG along the basement membrane of CEAN,while as the little nerve fibers grew outsite CEAN.
ⅡThe NGF was detected from the complicated controlled release drug of NGF at least 60 days and the bioactivity of released NGF stimulated the neuritis growth of chick dorsal root ganglion.At second week after nerve repair,the datum showed that the length of nerve regeneration in autografting was larger than the other groups (P＜0.05),NGF-treated acellular grafting better than acellular grafting alone and acellular grafting with fibrin glue(P＜0.05),and there were no difference between acellular grafting alone and acellular grafting with fibrin glue.Four months after nerve repair,nerve regeneration was assessed functionally and histomorphometrically. The percentage of the triceps surae muscular tension in autografting were better than the other groups(P＜0.05).There were no significant differences between the other three groups(P＜0.05).The percentage of the triceps surae weight in autografting were better than the other groups(P＜0.05),and that in NGF-treated acellular grafting better than the other two control group(P＜0.05).There were no significant differences between acellular grafting alone and acellular grafting with fibrin glue (P＜0.05).Based on the histological observation,the image analysis indicated that axonal diameter,axon number and myelin thickness in NGF-treated acellular grafting were better than those in acellular grafting alone and acellular grafting with fibrin glue (P＜0.05).There were no significant differences between NGF-treated acellular grafting and autografting.
ⅢThe slice of CEAN degraded by chondroitin enzamy ABC was immunohistochemistrily dyed:the CSPG could be degraded by chondroitin enzamy ABC and the laminin could be perserved.Animal experiment evaluated by functional and histological accessment 12 weeks after operation showed that there was autotomy in both groups.There was only one of 6 rats that had autotomy foot in A group but 6 of 8 rats in B group.Assessment of autotomy was carried out using the scale described by Wall,there were significant difference between both groups(P＜0.05). Five of six rats had positive pain reaction test in A group while as 1 of 8 rats did in B group.There were significant difference between them according to Chi-square test of four-fold table was performed(P＜0.05).The percentage of the triceps surae muscular tension and triceps surae weight in A group were better than the B group(P＜0.05). Nerve fibers structure dyed by HE staining were better in A group than in B group.
Conclusions:
1 There was no myelin protein remained in the CEAN,while the basement membrane structure of CEAN can induce the nerve fiber growing.
2 NGF bioactivity can be protected by NGF complicated controlled release drug. The speed of peripheral nerve regeneration can be improved repaired by CEAN with NGF complicated controlled release drug.
3 CSPG can be removed from the CEAN degraded by chondroitin enzyme ABC. Chondroitinase treatment increases the effective length of acellular nerve grafts.
周围神经损伤是临床上的难题,目前依然以自体神经移植修复为主要手段,但由于自体神经来源有限且供区有较多并发症,故多年来医学界不断寻找能替代自体神经移植的生物材料。在众多的替代材料中,去细胞异体神经显示了良好的应用前景。化学法萃取去细胞异体神经(Chemically ExtractedAcellular Nerve,CEAN),在最大限度地去除免疫原性物质的同时,较好地保存神经内部结构和细胞外基质的活性成分,成为修复周围神经缺损理想材料之一。
在我们前期的研究中,已经采用CEAN成功地修复了犬、猴的大段周围神经缺损,取得了良好效果,其有效修复长度范围可达8厘米。应用CEAN桥接周围神经损伤伤后,在再生神经纤维长入靶器官之前,患侧肌肉已发生严重萎缩,提高神经纤维再生速度,减轻肌肉萎缩对修复神经功能至关重要。此外,随着周围神经缺损长度的增加,神经修复效果降低,如何增加移植神经修复长度,已成为周围神经损伤研究重点之一。
相关的研究发现,CEAN中存在有利于神经生长的成分,也有不利于神经再生的成分,将这些抑制神经再生的物质去除,并保留促神经再生的物质,将进一步提高CEAN修复周围神经缺损效果。
研究目的
1对大鼠CEAN蛋白成分进行电泳分析,了解CEAN中免疫原性蛋白残存情况;在CEAN切片上,接种背根神经节,观察CEAN结构对神经再生的影响。
2为CEAN修复周围神经缺损补充缓释的外源性神经生长因子,观察该方法对神经再生生长速度、肌肉萎缩、神经组织再生情况的影响。
3应用软骨素酶ABC去除CEAN中不利于神经再生的物质-硫酸软骨素蛋白多糖(Chondroitin Sulfate Proteoglycan,CSPG),修复大鼠坐骨神经长距离缺损,评价去除CSPG对修复缺损距离的影响。
研究方法
第一部分CEAN蛋白成分及结构特性
按Sondell法制备大鼠的CEAN,将制备好的CEAN进行电泳分析,观察28-30 kDa区域的髓鞘蛋白的残留情况;将CEAN进行冰冻切片,接种鸡胚背根神经节,进行神经纤维荧光染色,观察神经纤维在CEAN切片上的生长方向。
第二部分神经生长因子(NGF)复合缓释制剂对提高CEAN修复周围神经缺损的实验研究
采用复乳溶媒蒸发—萃取法,以聚乳酸羟基/乙酸共聚物为材料制备NGF微球,与纤维蛋白胶混合制备成补充外源性NGF复合缓释制剂。体外进行NGF复合缓剂药物释放曲线,与鸡胚背根神经节共培养鉴定释放NGF的活性。体内实验,以桥接大鼠坐骨神经10mm缺损为模型,分为自体神经移植组(A组),CEAN+NGF复合缓释制剂组(B组);CEAN移植组(C组):CEAN移植+纤维蛋白胶组(D组),术后两周测量神经再生生长距离,术后4个月进行神经电生理、腓肠肌湿重、计算机图像分析等方面评价神经移植后的再生效果。
第三部分去除CEAN中的CSPG对修复周围神经缺损的实验研究
CEAN经软骨素酶ABC降解CSPG后,进行免疫组化染色,观察CSPG去除效果和对去细胞异体神经其它成分的影响。经软骨素酶ABC处理后的CSPG修复周围神经缺损为实验组(A组),桥接大鼠20mm周围神经缺损,对照组不作处理(B组),术后3个月,评价其修复周围神经效果。
研究结果
第一部分:CEAN电泳结果显示:28-30kDa区域髓鞘蛋白完全消失,化学萃取的去细胞神经可以完全去除髓鞘蛋白;背根神经节发出大量的神经纤维沿着CEAN基底膜管方向生长;而CEAN切片外侧仅有少量神经纤维生长。
第二部分:体外实验证明,NGF复合缓释制剂可持续释放NGF达60天以上,释出的NGF可促进鸡胚背根神经节神经纤维突起生长,具有较强的生物学活性。术后2周A组神经再生距离比其他组长(P＜0.05),B组优于C和D组(P＜0.05);C、D组间无差异无统计学意义(P＜0.05)。术后16周,A、B、C及D组小腿三头肌收缩力恢复率分别为85.33%±5.59%、69.79%±5.31%、64.46%±8.49%、63.35%±6.40%;A组优于其他3组(P＜0.05),B、C、D组间差异无统计学意义(P＜0.05)。A、B、C及D组肌肉湿重恢复率分别为62.54%±8.25%、53.73%±4.56%、46.37%±5.68%、45.78%±7.14%;A组三头肌湿重恢复率好于其他3组(P＜0.05),B组好于C和D组(P＜0.05);C、D组间无差异无统计学意义(P＜0.05)。组织学图像分析结果为B组在有髓神经纤维数量,轴突直径,髓鞘厚度,均优于C、D组(P＜0.05),轴突直径小于与A组(P＜0.05)。
第三部分:CSPG免疫组化染色结果显示,软骨素酶ABC可以明显去除CSPG,并保留促神经生长的Laminin有效成分。动物实验结果显示,术后2个月,两组都出现残足情况,A组仅一只大鼠出现残足,而B组6只大鼠出现残足。据Wall自残标准评分,两组进行等级资料秩和检验,P＜0.05,两者之间具有统计学差异。术后3个月,A组6只大鼠5只出现钳夹痛觉试验阳性,而B组仅1只大鼠出现阳性反应。进行四格表卡方检验,x~2=4.42,P＜0.05。两组之间具有显著性差异。在小腿三头肌肌张力恢复率和小腿三头肌肌湿重方面,两组比较,A组均优于B组。进行近端与远端吻合口HE染色A组神经纤维结构优于B组。
结论
1 CEAN中无残留引起免疫反应的髓鞘蛋白,保留的基底膜管结构对促神经纤维再生具有引导性作用。
2 NGF复合缓释制剂可以保护NGF活性,可以提高CEAN修复周围神经缺损的神经再生速度。
3软骨素酶ABC可以去除CEAN中CSPG,经软骨素酶ABC处理的CEAN可以增加修复周围神经缺损的长度。
Background:The treatment of peripheral nerve injury is a tough problem clinically. The standard clinical approach for bridging nerve defects is an autologous nerve graft, or autograft.Disadvantages of the autograft include limitation of the source of autologous nerve and loss of function at the donor site.Therefore,many researchs are focused on developing proper biomaterials as an alternate to autograft.Chemically extracted acellular nerve allograft(CEAN) which removes immunogenicity such as Schwann cells and myelin while restoring the nerve structures such as basal lamina tubes and extracellular matrix,is a promising material alternative to autograft.In nerve grafting,muscles may show irreversible atrophy and lose function before axonal regeneration into the distal targets.For CEAN,the speed of recovery of nerves regeneration must be increased and muscle atrophy decreased.In addition,the results of repiring the peripheral nerve defect with CEAN became worse while the length of peripheral nerve defect increasing.It becomes an important research subject that how to increase the length of repairing peripheral nerve defect.
Objective:
1.Electrophoretic analysis of rat CEAN protein is to be performed to know about the protein of CEAN.Dorsal root ganglia of chicken are cultured onto the surface of CEAN slice in order to observe the effect of CEAN structure on the fiber regeneration.
2.Sustained of nerve growth factor is to be deliveried for CEAN,used to repair injured nerves,to evaluate effect of the method on the speed of nerve regeneration, muscular atrophy and nerve tissue regeneration.
3.The protein of Chondroitin Sulfate Proteoglycan(CSPG) in CEAN is to be degraded by Chondroitin enzyme ABC,and the peripheral nerve large defects is to be repaired with these CEAN in order to evaluate the effect of degrading Chondroitin sulfate proteoglycan of CEAN on the length of repairing nerve defects. Methods:
ⅠThe protein and structure characteristics of CEAN The CEAN were perpared according to Sondell method and electrophoresed to observed whether the electrophoresis strip of 28-30kDa(Myelin Protein) exited or not.Dorsal root ganglia of chicken was cultured onto the surface of CEAN slice and dyed with nerve fiber fluorescence to observe the orientation of nerve fiber growth on the surface of CEAN slice.
ⅡExperiment on the effect of controlled nerve growth factor on peripheral nerve defect repaired by CEAN
The microspheres of NGF were prepared drug microsphere technology and fixed with the fibrin gels to make the complicated controlled release NGF.The Wister rats were randomly divided into four groups:Autograft group(A group),acellular nerve allograft+the double controlled release NGF(B group),acellular nerve allograft(C group) and acellular nerve allograft+fibrin glue(D group).The nerve regeneration length was measured 2 weeks after operation.The effects of peripheral nerve regeneration were evaluated by neural electrophysiology,the recovery rate of triceps surae muscular tension and weight and histological assessment 4 monthes after operation.
ⅢEffect of CSPG degraded by Chondroitin enzyme ABC in CEAN on repairing peripheral nerve defect
CEAN of which chondroitin sulfate proteoglycan was degraded by chondroitin enzyme ABC was immunohistochemistrily dyed with anti-CSPG in order to observe the remain of chondroitin sulfate proteoglycan and the other elements in CEAN.The Wister rats which left sciatic nerve was cut for 20 mm defect were randomly divided into two groups:CEAN degraded by chondroitin enzyme ABC(A group),CEAN(B group).The result of nerve regeneration was evaluated 3 monthes after operation.
Results:
ⅠElectrophoretic analysis of rat CEAN protein showed that the electrophoresis strip of 28-30kDa was totally disappeared.The large number of nerve fibers growed from DRG along the basement membrane of CEAN,while as the little nerve fibers grew outsite CEAN.
ⅡThe NGF was detected from the complicated controlled release drug of NGF at least 60 days and the bioactivity of released NGF stimulated the neuritis growth of chick dorsal root ganglion.At second week after nerve repair,the datum showed that the length of nerve regeneration in autografting was larger than the other groups (P＜0.05),NGF-treated acellular grafting better than acellular grafting alone and acellular grafting with fibrin glue(P＜0.05),and there were no difference between acellular grafting alone and acellular grafting with fibrin glue.Four months after nerve repair,nerve regeneration was assessed functionally and histomorphometrically. The percentage of the triceps surae muscular tension in autografting were better than the other groups(P＜0.05).There were no significant differences between the other three groups(P＜0.05).The percentage of the triceps surae weight in autografting were better than the other groups(P＜0.05),and that in NGF-treated acellular grafting better than the other two control group(P＜0.05).There were no significant differences between acellular grafting alone and acellular grafting with fibrin glue (P＜0.05).Based on the histological observation,the image analysis indicated that axonal diameter,axon number and myelin thickness in NGF-treated acellular grafting were better than those in acellular grafting alone and acellular grafting with fibrin glue (P＜0.05).There were no significant differences between NGF-treated acellular grafting and autografting.
ⅢThe slice of CEAN degraded by chondroitin enzamy ABC was immunohistochemistrily dyed:the CSPG could be degraded by chondroitin enzamy ABC and the laminin could be perserved.Animal experiment evaluated by functional and histological accessment 12 weeks after operation showed that there was autotomy in both groups.There was only one of 6 rats that had autotomy foot in A group but 6 of 8 rats in B group.Assessment of autotomy was carried out using the scale described by Wall,there were significant difference between both groups(P＜0.05). Five of six rats had positive pain reaction test in A group while as 1 of 8 rats did in B group.There were significant difference between them according to Chi-square test of four-fold table was performed(P＜0.05).The percentage of the triceps surae muscular tension and triceps surae weight in A group were better than the B group(P＜0.05). Nerve fibers structure dyed by HE staining were better in A group than in B group.
Conclusions:
1 There was no myelin protein remained in the CEAN,while the basement membrane structure of CEAN can induce the nerve fiber growing.
2 NGF bioactivity can be protected by NGF complicated controlled release drug. The speed of peripheral nerve regeneration can be improved repaired by CEAN with NGF complicated controlled release drug.
3 CSPG can be removed from the CEAN degraded by chondroitin enzyme ABC. Chondroitinase treatment increases the effective length of acellular nerve grafts.
引文
1.Dumont CE,Hentz VR.Enhancement of axon growth by detergent-extracted nerve grafts.Transplantation,1997,63:1210-1215.
2.Sondell M,Lundborg G,Kanje M.Regeneration of the rat sciatic nerve into allografts made acellular through chemical extraction.Brain Res,1998,795:44-54.
3.衷鸿宾,卢世璧,赵庆,等.犬化学去细胞神经同种异体移植的神经再生研究.中华手外科杂志,2002,18:131-133.
4 衷鸿宾,卢世璧,赵庆,等.去细胞神经同种异体移植的运动功能恢复.中华创伤杂志,2002,18:533-535.
5.郭义柱,卢世璧,王岩,等.去细胞同种异体神经移植修复人体长段周围神经缺损.中国临床康复,2005,9(38):26-27.
6.Levi-Montalcini R,Skaper SD,Toso RD,et al.Nerve growth factor:from neurot -rophin to neurokine.Trends in Neurosci,1996,19(11):514-520.
7.Terenghi G.Peripheral nerve regeneration and neurotrophic factors.J Anatomy,1999,194:1-14.
8.Aloe L.Rita Levi-Montalcini:the discovery of nerve growth factor and modern neurobiology.Trends in Cell Biology,2004,14(7):395-399.
9.Gravvanis AI,Tsoutsos DA,Tagaris GA,et al.Beneficial effect of nerve growth factor-7S on peripheral nerve regeneration through inside-out vein grafts:An ex -perimental study.Microsurgery,2004,24(5):408-415.
10.Tsai CC,Lu MC,Chen YS,et al.Locally administered nerve growth factor supp -resses ginsenoside Rbl-enhanced peripheral nerve regeneration.Am J Chin Med,2003,31(5):665-673.
11.Camarata P J,Suryanarayanan R,Turner DA,et al.Sustained release of nerve growth factor from biodegradable polymer microspheres.Neurosurgery,1992,30(3):313-319.
12.Hadlock TA,Sheahan T,Cheney ML,et al.Biologic activity of nerve growth factor slowly released from microspheres.Biomaterials,2002,23(17):3765-3772.
13.Xiaoyun Xu,Harry Yu,Shujun Gao,et al.Polyphosphoester microshperes for sustained release of biologically active nerve growth factor.Biomaterials,2002, 23:3765-3722.
4.Xu X,Yee WC,Hwang PY,et al.Peripheral nerve regeneration with sustained release of poly(phosphoester) microencapsulated nerve growth factor within nerve guide conduits.Biomaterials,2003,24(13):2405-2412.
5.Jockenhoevel S,Zund G,Hoerstrup SP,et al.Fibrin gel-advantages of a new scaffold in cardiovascular tissue engineering.Eur J Cardiothorac Surg,2001,19(4):424-430.
6.Herbert CB,Bittner GD,Hubbell JA.Effects of fibinolysis on neurite growth from dorsal root ganglia cultured in two-and three-dimensional fibrin gels.J Comp Neurol,1996,365(3):380-391.
7.Lee AC,Yu VM,Lowe JB,et al.Controlled release of nerve growth factor enhances sciatic nerve regeneration.Exp Neurol,2003,184(1):295-303.
18.Previtali SC,Nodari A,Taveggia C,et al.Expression of laminin receptors in schwann cell differentiation:evidence for distinct roles.J Neurosci,2003,23(13):5520-5530.
19.Chen ZL,Strickland S.Laminin gammal is critical for Schwann cell differentia -tion,axon myelination,and regeneration in the peripheral nerve.J Cell Biol,2003,163(4):889-899.
20.Ferguson TA,Muir D.MMP-2 and MMP-9 increase the neurite-promoting poten -tial of Schwann cell basal laminae and are upregulated in degenerated nerve.Mol Cell Neurosci,2000,16(2):157-167.
21.Trigg D J,O'Grady KM,Bhattacharyya T,Reinke M,Toriumi DM.Peripheral nerve regeneration:comparison of laminin and acidic fibroblast growth factor.Am J Otolaryngol,1998,19(1):29-32.
22.Uziyel Y,Hall S,Cohen J.Influence of laminin-2 on Schwann cell-axon interacts -ions.Glia,2000,32(2):109-121.
23.王国英,平井圭一,钟世镇,等.雪旺氏细胞基底膜成分 laminin 在神经再生中的作用探讨.中国临床解剖杂志,1992,10(3):200-207.
24.Le Beau JM,Liuzzi FJ,Depto AS,et al.Up-regulation of laminin B2 gene expres -sion in dorsal root ganglion neurons and nonneuronal cells during sciatic nerve regeneration.Exp Neurol,1995,134(1):150-155.
25.Martini R.Expression and functional roles of neural cell surface molecules and extracellular matrix components during development and regeneration of peripheral nerves.J Neurocytol,1994,23(1):1-28.
26.Agius E,Cochard P.Comparison of neurite outgrowth induced by intact and injured sciatic nerves:a confocal and functional analysis.J Neurosci,1998,18(1):328-38.
27.Bovolenta P,Fernaud-Espinosa I.Nervous system proteoglycans as modulators of neurite outgrowth.Prog Neurobiol,2000,61(2):113-132.
28.Lander AD,Fujii DK,Reichardt LF.Purification of a factor that promotes neurite outgrowth:isolation of laminin and associated molecules.J Cell Biol,1985,101(3):898-913.
29.Okada N,Tanaka H,Takizawa H,et al.A monoclonal antibody that blocks the complement regulatory activity of guinea pig erythrocytes and characterization of the antigen involved as guinea pig decay-accelerating factor.J Immunol,1995,154(11):6103-6111.
30.Cole GJ,Loewy A,Glaser L.Neuronal cell-cell adhesion depends on interactions of N-CAM with heparin-like molecules.Nature,1986,320(6061):445-447.
31.Hantaz-Ambroise D,Vigny M,Koenig J.Heparan sulfate proteoglycan and lamin -in mediate two different types of neurite outgrowth.J Neurosci,1987,7(8):2293-2304.
32.Dou CL,Levine JM.Inhibition of neurite growth by the NG2 chondroitin sulfa -te proteoglycan.J Neurosci,1994,14(12):7616-7628.
33.Fidler PS,Schuette K,Asher RA,et al.Comparing astrocytic cell lines that are in -hibitory or permissive for axon growth:the major axon-inhibitory proteoglycan is NG2.J Neurosci,1999,19(20):8778-8788.
34.McKeon RJ,Hoke A,Silver J.Injury-induced proteoglycans inhibit the potential for laminin-mediated axon growth on astrocytic scars.Exp Neurol,1995,136(1):32-43.
35.Muir D,Engvall E,Varon S,Manthorpe M.Schwannoma cell-derived inhibitor of the neurite-promoting activity of laminin.J Cell Biol,1989,109(5):2353-62.
36.Schmalfeldt M,Bandtlow CE,Dours-Zimmermann MT,et al.Brain derived versi-can V2 is a potent inhibitor of axonal growth.J Cell Sci,2000,113:807-816.
37.Snow DM,Lemmon V,Carrino DA,e al.Sulfated proteoglycans in astroglial barriers inhibit neurite outgrowth in vitro.Exp Neurol,1990,109 (1):111-130.
38.Ughrin YM,Chen ZJ,Levine JM.Multiple regions of the NG2 proteoglycan inhibit neurite growth and induce growth cone collapse.J Neurosci,2003,23 (1):175-186.
39.Jones LL,Sajed D,Tuszynski MH.Axonal regeneration through regions of chon -droitin sulfate proteoglycan deposition after spinal cord injury:a balance of per-missiveness and inhibition.J Neurosci,2003,23(28):9276-9288.
40.Zuo J,Ferguson TA,Hernandez YJ,et al.Neuronal matrix metalloproteinase-2 degrades and inactivates a neurite-inhibiting chondroitin sulfate proteoglycan.J Neurosci,1998,18(14):5203-5211.
41.Baichwal RR,Bigbee JW,DeVries GH.Macrophage-mediated myelin-related mitogenic factor for cultured Schwann cells.Proc Natl Acad Sci USA,1988 85(5):1701-1705.
1.Dumont,CE,Hentz VR.Enhancement of axon growth by detergent-extracted nerve grafts.Transplantation,1997,63(9):1210-1215.
2.Sondell,MG,Lundborg,Kanje M.Regeneration of the rat sciatic nerve into allografts made acellular through chemical extraction.Brain Res,1998,795(1-2):44-54.
3.戴传昌,王炜,曹谊林,等.去细胞异体神经基膜管桥接神经缺损的实验研究.中华整形外科杂志,2001,17:366-368.
4.王建云.化学萃取同种异体神经种植许旺细胞的体外实验.中华显微外科杂志,2002,25:189-191.
5.Sun MX,Lu SB,Tang JS.Experimental study on repairing different length nerve defects with chemical extracted acellular nerve allograft.Orthopedic Journal of China,2006,14:603-607.
6.Verdu E,Labrador RO,Rodringuez F J,et al.Alignment of collagen and laminin-containing gels improve nerve regeneration within silicone tubes.Restor Neurol Neurosci,2002,20(5):169-79.
7.Dubovy P,Svizenska I,Klusakova I,et al.Laminin molecules in freeze-treated nerve segments are associated with migrating Schwann cells that display the corresponding alpha6betal integrin receptor.Glia,2001,33(1):36-44.
8.Fawcett JW,Keynes RJ.Peripheral nerve regeneration.Annu Rev Neurosci,1990,13:43-60.
9.Ide C,Osawa T,Tohyama K.Nerve regeneration through allogeneic nerve grafts,with special reference to the role of the Schwann cell basal lamina.Prog Neurobiol,1990,34(1):1-38.
10.Hudson TW,Liu SY,Schmidt CE.Engineering an improved acellular nerve graft via optimized chemical processing.Tissue Eng,2004,10(9-10):1346-58.
11.Hudson TW,Zawko S,Deister C,et al.Optimized acellular nerve graft is immunologically tolerated and supports regeneration.Tissue Eng,2004,10(11-12):1641-51.
12.Givogri MI,Bongarzone ER,Campagnoni AT.New insights on the biology of myelin basic protein gene:the neural-immune connection.J Neurosci Res,2000,59(2):153-9.
13.Lassner F,Schaller E,Steinhoff,et al.Cellular mechanisms of rejection and regeneration in peripheral nerve allografts.Transplantation,1989,48(3):386-92.
14.Mackinnon SE,Dellon AL.Clinical nerve reconstruction with a bioabsorbable polyglycolic acid tube.Plast Reconstr Surg,1990,85(3):419-24.
15.Meek MF,Den Dunnen WF,Schakenraad JM,et al.Long-term evaluation of functional nerve recovery after reconstruction with a thin-walled biodegradable poly(DL-lactide-epsilon-aprolactone) nerve guide,using walking track analysis and electrostimulation tests.Microsurgery,1999,19(5):247-53.
16.Li ST,Archibaid S J,Krarup C,et al.Peripheral nerve repair with collagen conduits.Clin Mater,1992,9(3-4):195-200.
17.Shaw D,Shoichet MS.Toward spinal cord injury repair strategies:peptide surface modification of expanded poly(tetrafluoroethylene) fibers for guided neurite outgrowth in vitro.J Craniofac Surg,2003,14(3):308-16.
18.Bozkurt A,Deumens R,Beckmann C,et al.In vitro cell alignment obtained with a Schwann cell enriched microstructured nerve guide with longitudinal guidance channels.Biomaterials,2009,30(2):169-79.
19.李立钧,陈统一.周围神经损伤与再生中的细胞和细胞因子.国外医学.骨科学分册,2004,25:280-283.
1.Levi-Montalcini R,Skaper SD,Toso RD,et al.Nerve growth factor:from neurot-rophin to neurokine.Trends in Neurosci,1996,19(11):514-520.
2.Xiaoyun Xu,Harry Yu,Shujun Gao,et al.Polyphosphoester microshperes for sustained release of biologically active nerve growth factor.Biomaterials,2002,23:3765-3722.
3.Terenghi G.Peripheral nerve regeneration and neurotrophic factors.J Anatomy,1999,194:1-14.
4.Aloe L.Rita Levi-Montalcini:the discovery of nerve growth factor and modern neurobiology.Trends in Cell Biology,2004,14(7):395-399.
5.Gravvanis Al,Tsoutsos DA,Tagaris GA,et al.Beneficial effect of nerve growth factor-7S on peripheral nerve regeneration through inside-out vein grafts:An experimental study.Microsurgery,2004,24(5):408-415.
6.Tsai CC,Lu MC,Chen YS,et al.Locally administered nerve growth factor suppresses ginsenoside Rb1-enhanced peripheral nerve regeneratioa Am J Chin Med,2003,31(5):665-673.
7.Xiaoyun Xua,Woon-Chee Yeeb,Peter YK,et al.Peripheral nerve regeneration with sustained release of poly(phosphoester) microencapsulated nerve growth factor within nerve guide conduits.Biomaterials,2003,24(13):2405-2412.
8.Bhang SH,Jeon O,Choi CY,et al.Controlled release of Nerve growth factor from fibrin gel.J Biomed Mater Res A,2007,80(4):998-1002.
9.Camarata PJ,Suryanarayanan R,Turner DA,et al.Sustained nerve growth factor from biodegradable polymer microsphere.Neurosurgery,1992,30(3):313-319.
1.徐杨,陈统一.周围神经修复方法进展.国外医学·骨科学分册,2004,25(5):270-274.
2.Sondell M,Lundborg G,Kanje M.Regeneration of the rat sciatic nerve into allografts made acellular through chemical extraction.Brain Res,1998,795(1-2):44-54.
3.Hudson TW,Liu SY,Schmidt CE.Engineering an improved acellular nerve graft via optimized chemical processing.Tissue Eng,2004,10(9-10):1346-1358.
4.Levi-Montalcini R,Skaper SD,Dal Toso R,et al.Nerve growth factor:from neurotrophin to neurokine.Trends Neurosci,1996,19(11):514-520.
5.王冠军,孙明学,卢世璧,等.改良化学去细胞同种异体神经制备方法的实验研究.中国矫形外科杂志,2007,15(12):929-932.
6.Lee AC,Yu VM,Lowe JB 3rd,et al.Controlled release of nerve growth factor enhances sciatic nerve regeneration.Exp Neurol,2003,184(1):295-303.
7.Xu X,Yee WC,Hwang PY,et al.Peripheral nerve regeneration with sustained release of poly(phosphoester) microencapsulated nerve growth factor within nerve guide conduits.Biomaterials,2003,24(13):2405-2412.
8.Zhu JY,Huang YT,Zhu QS,et al.Expression of adenovirus-mediated neurotrophin-3 gene in Schwann cells of sciatic nerve in rats.Chin J Traumatol,2003,6(2):75-80.
9.Aloe L.Rita Levi-Montalcini:the discovery of nerve growth factor and modern neurobiology.Trends Cell Biol,2004,14(7):395-399.
10.Gravvanis AI,Tsoutsos DA,Tagaris GA,et al.Beneficial effect of nerve growth factor-7S on peripheral nerve regeneration through inside-out vein grafts:an experimental study.Microsurgery,2004,24(5):408-415.
11.Tsai CC,Lu MC,Chen YS,et al.Locally administered nerve growth factor suppresses ginsenoside Rb1-enhanced peripheral nerve regeneration.Am J Chin Med,2003,31(5):665-673.
12.Kim BS,Yoo J J,Atala A.Peripheral nerve regeneration using acellular nerve grafts.J Biomed Mater Res A,2004,68(2):201-209.
13.孙明学,王鑫,赵斌,等.化学去细胞法对粗大神经质量评价方法及影响因素的探讨.中国修复重建外科杂志,2006,20(8):779-782.
14.Yoshimura K,Harii K.A regenerative change during muscle adaptation to denervation in rats.J Surg Res,1999,81(2):139-146.
15.赵磊,严志强,吕广明.失神经支配骨髂肌的萎缩机制.中国组织工程研究与临床康复,2007,11(6):1120-1122.
16.Lee DY,Choi BH,Park JH,et al.Nerve regeneration with the use of a poly(1-lactide-co-glycolic acid)-coated collagen tube filled with collagen gel.J Craniomaxillofac Surg,2006,34(1):50-56.
1.顾立强,裴国献．周围神经损伤与临床．人民军医出版社,2001：100-101．
2.Muir D,Engvall E,Varon S,et al.Schwannoma cell-derived inhibitor of the neurite-promoting activity of laminin.J Cell Biol,1989,109(5):2353-2362.
3.Snow DM,Lemmon V,Carrino DA,et al.Sulfated proteoglycans in astroglial barriers inhibit neurite outgrowth in vitro.Exp Neurol,1990,109(1):111-130.
4.Brittis PA,Canning DR,Silver J.Chondroitin sulfate as a regulator of neuronal patterning in the retina.Science,1992,255(5045):733-736.
5.McKeon RJ,Hoke A,Silver J.Injury-induced proteoglycans inhibit the potential for laminin-mediated axon growth on astrocytic scars.Exp Neurol,1995,136(1):32-43.
6.Friedman JA,Windebank AJ,Moore MJ,et al.Biodegradable polymer grafts for surgical repair of the injured spinal cord.Neurosurgery,2002,51(3):742-751.
7.Zuo J,Hernandez YJ,Muir D.Chondroitin sulfate proteoglycan with neurite-inhibiting activity is up-regulated following peripheral nerve injury.Journal of Neurobiology,1998 b,34(1):41-54.
8.Zuo J,Neubauer D,Dyess K,et al.Degradation of chondroitin sulfate proteoglycan enhances the neurite-promoting potential of spinal cord tissue.Exp Neurol,1998,154(2):654-662.
9.Bedi KS,Winter J,Berry M,et al.Adult Rat Dorsal Root Ganglion Neurons Extend Neurites on Predegenerated But Not on Normal Peripheral Nerves In Vitro.Eur J Neurosci,1992,4(3):193-200.
10.Agius E,Cochard P.Comparison of neurite outgrowth induced by intact and injured sciatic nerves:a confocal and functional analysis.J Neurosci,1998,18(1):328-338.
11.Danielsen N,Kerms JM,Holmquist B,et al.Pre-degenerated nerve grafts enhance regeneration by shortening the initial delay period.Brain Res,1994,666(2):250-254.
12.Chan YM,Wu W,Yip HK,et al.Caspase inhibitors promote the survival of avulsed spinal motoneurons in neonatal rats.Neuroreport,2001,12(3):541-545.
13.Hammarberg H,Piehl F,Risling M,et al.Differential regulation of trophic factor receptor mRNAs in spinal motoneurons after sciatic nerve transection and ventral root avulsion in the rat.J Comp Neurol,2000,426(4):587-601.
14.Shi TJ,Tandrup T,Bergman E,et al.Effect of peripheral nerve injury on dorsal root ganglion neurons in the C57 BL/6J mouse:marked changes both in cell numbers and neuropeptide expression.Neuroscience,2001,105(1):249-263.
15.Zuo J,Ferguson TA,Hernandez YJ,et al.Neuronal matrix metalloproteinase-2 degrades and inactivates a neurite-inhibiting chondroitin sulfate proteoglycan.Journal of Neuroscience,1998,18(14):5203-5211.
16.Zuo J,Neubauer D,Graham J,et al.Regeneration of axons after nerve transection repair is enhanced by degradation of chondroitin sulfate proteoglycan.Experimental Neurology,2002,176(1):221-228.
17.Hudson TW,Liu SY,Schmidt CE.Engineering an improved acellular nerve graft via optimized chemical processing.Tissue Eng,2004,10(9-10):1346-1358.
18.Hudson TW,Zawko S,Deister C,et al.Optimized acellular nerve graft is immunologically tolerated and supports regeneration.Tissue Eng,2004,10(11-12):1641-1651.
1.Dumont C E,Hentz VR.Enhancement of axon growth by detergent-extracted nerve grafts.Transplantation,1997,63(9):1210-5.
2.Sondell M,Lundbor G,Kanje M.Regeneration of the rat sciatic nerve into allografts made acellular through chemical extraction.Brain Res,1998,795(1-2):44-54.
3.Gulati AK.Evaluation of acellular and cellular nerve grafts in repair of rat peripheral nerve.J Neurosurg,1988,68(1):117-123.
4.Nadim W,Anderson PN,Turmaine M.The role of Schwann cells and basal lamina tubes in the regeneration of axons through long lengths of freeze-killed nerve grafts.Neuropathol Appl Neurobiol,1990,16(5):411-421.
5.Danielsen N,Kerms JM,Holmquist B,et al.Pre-degenerated nerve grafts enhance regeneration by shortening the initial delay period.Brain Res,1994,666(2):250-254.
6.Krekoski CA,Neubauer D,Graham JB,et al.Metalloproteinase-dependent predegeneration in vitro enhances axonal regeneration within acellular peripheral nerve grafts.J Neurosci,2002,22(23):10408-15.
7.Krekoski CA,Neubauer D,Zuo J,et al.Axonal regeneration into acellular nerve grafts is enhanced by degradation of chondroitin sulfate proteoglycan.Journal of Neuroscience,2001,21(16):6206-6213.
8.Jubran M,Widenfalk J.Repair of peripheral nerve transections with fibrin sealant containing neurotrophic factors.Exp Neurol,2003,181(2):204-212.
9.Fawcett JW,Keynes RJ.Peripheral nerve regeneration.Annu Rev Neurosci,1990,13:43-60.
10.Tohyama K,Ide C,Osawa T.Nerve regeneration through the cryo injured allogeneic nerve graft in the rabbit.Acta Neuropathol,1990,80(2):138-144.
11.Chong MS,Woolf CJ,Andrews P,et al.The downregulation of GAP-43 is not responsible for the failure of regeneration in freeze-killed nerve grafts in the rat.Exp Neurol,1994,129(2):311-20.
12.Ochi M,Wakasa M,Ikuta Y,et al.Nerve regeneration in predegenerated basal lamina graft:the effect of duration of predegeneration on axonal extension.Exp Neurol,1994,128(2):216-25.
13.Zuo J,Hernandez Y J,Muir D.Chondroitin sulfate proteoglycan with neuriteinhibiting activity is up-regulated following peripheral nerve injury.J Neurobiol,1998,34(1):41-54.
14.Ferguson TA,Muir D.MMP-2 and MMP-9 increase the neurite-promoting potential of schwann cell basal laminae and are upregulated in degenerated nerve.Mol Cell Neurosci,2000,16(2):157-167.
15.Muir D,Engvall E,Varon S,et al.Schwannoma cell-derived inhibitor of the neurite-promoting activity of laminin.J Cell Biol,1989,109(5):2353-2562.
16.Zuo J,Neubauer D,Dyess K,et al.Degradation of chondroitin sulfate proteoglycan enhances the neurite-promoting potential of spinal cord tissue.Exp Neurol,1998,154(2):654-662.
17.Yoshimura K,Harii K.A regenerative change during muscle adaptation to denervation in rats.J Surg Res,1999,81(2):139-46.
18.赵磊,严志强,吕广明.失神经支配骨骼肌的萎缩机制.中国组织工程研究与临床康复,2007,11(6):1120-1122.
1.Lundborg G.Alternatives to autologous nerve grafts.Handchir Mikrochir Plast Chir,2004,36(1):1-7.
2.Schmidt CE,Leach JB.Neural tissue engineering:strategies for repair and regeneration.Annu Rev Biomed Eng,2003,5:293-296.
3.Raimondo S,Nicolino S,Tos P,et al.Schwann cell behavior after nerve repair by means of tissue-engineered muscle-vein combined guides.J Comp Neurol,2005,489(2):249-259.
4.Hudson TW,Liu SY,Schmidt CE.Engineering an improved acellular nerve graft via optimized chemical processing.Tissue Eng,2004,10(9-10):1346-1358
5.Hudson TW,Evans GR,Schmidt CE.Engineering strategies for peripheral nerve repair.Clin Plast Surg,1999,26(4):617-628
6.张自杰,朱家恺.获得大量雪旺氏细胞的方法学研究.中华显微外科杂志,1992,15(2):87-89.
7.Patrick CW,Zheng B,Schmidt M,et al.Dermal fibroblasts genetically engineered to release NGF.Ann Plast Surg,2001,47(6):660-665.
8.Jimenez JC,Tyson DR,Dhar S,et al.Human embryonic kidney cells(HEK-293):characterization and dose response for modulated release of NGF for nerve regeneration.Plast Reconstr Surg,2004,113(2):605-610.
9.McConnell MP,Dhar S,Nguyen T,et al.Nerve growth factor expression response to induction agent booster dosing in transfected human embryonic kidney cells.Plast Reconstr Surg,2005,115(2):506-514.
10.McConnell MP,Dhar S,Naran S,et al.In vivo induction and delivery of nerve growth factor,using HEK-293 cells.Tissue Eng,2004,10(9-10):1492-501.
11.Knight MA,Evans GR.Tissue engineering:progress and challenges.Plast Reconstr Surg,2004,114(2):26E-37E.
12.Dezawa M.Future views and challenges to the peripheral nerve regeneration by cell based therapy.Rinsho Shinkeigaku,2005,45(11):877-879.
13.Murakami T,Fujimoto Y,Yasunaga Y,et al.Transplanted neuronal progenitor cells in a peripheral nerve gap promote nerve repair.Brain Res,2003,974(1-2):17-24.
14.Heine W,Conant K,Griffin JW,et al.Transplanted neural stem cells promote axonal regeneration through chronically denervated peripheral nerves.Exp Neurol, 2004,189(2):231-240.
15.Morrison SJ,White PM,Zock C,et al.Prospective identification,isolation by flow cytometry,and in vivo self renewal of multipotent mammalian neural crest stem cells.Cell,1999,96(5):737-749.
16.Tohill M,Terenghi G.Stem cell plasticity and therapy for injuries of the peripheral nervous system.Biotechnol Appl Biochem,2004,40(pt1):17-24.
17.Amoh Y,Li L,Campillo R,et al.Implanted hair follicle stem cells form Schwann cells that support repair of severed peripheral nerves.Proc Natl Acad Sci USA,2005,102(48):17734-17738.
18.Woodbury D,Schwarz EJ,Prockop DJ,et al.Adult rat and human bone marrow stromal cells differentiate into neurons.J Neurosci Res,2000,61(4):364-370.
19.Sanchez-Ramos J,Song S,Cardozo-Pelaez F,et al.Adult bone marrow stromal cells differentiate into neural cells in vitro.Exp Neurol,2000,164(2):247-56.
20.Akiyama Y,Radtke C,Kocsis JD.Remyelination of the rat spinal cord by transplantation of identified bone marrow stromal cells.J Neurosci,2002,22(15):6623-6630.
21.Dezawa M,Takahashi I,Esaki M,et al.Sciatic nerve regeneration in rats induced by transplantation of in vitro differentiated bone-marrow stromal cells.Eur J Neurosci,2001,14(11):1771-1776.
22.DiStefano PS,Friedman B,Radziejewski C,et al.The neurotrophins BDNF,NT-3,and NGF display distinct patterns of retrograde axonal transport in peripheral and central neurons.Neuron,1992,8(5):983-993.
23.Fu SY,Gordon T.The cellular and molecular basis of peripheral nerve regeneration.Mol Neurobiol,1997,14(1-2):67-116.
24.Bampton ET,Taylor JS.Effects of Schwann cell secreted factors on PC 12 cell neuritogenesis and survival.J Neurobiol,2005,63(1):29-48.
25.Gravel C,Gotz R,Lorrain A,et al.Adenoviral gene transfer of ciliary neurotrophic factor and brain-derived neurotrophic factor leads to long-term survival of axotomized moter neurons.Nat Med,1997,3(7):765-770.
26.Rangappa N,Romero A,Nelson KD,et al.Laminin-coated poly (L-lactide) filaments induce robust neurite growth while providing directional orientation.Biomed Mater Res,2000,51(4):625-634.
27.Colognato H,Yurchenco PD.Form and function:the laminin family of heterotrimers.Dev Dyn,2002,18(2):213-234.
28.Kuhn TB,Williams CV,Dou P,et al.Laminin directs growth cone navigation via two temporally and functionally distinct calcium signals.Neurosci,1998,18(1):184-194.
29.Baron-Van Evercooren A,Kleinman HK,Seppa HE,el at.Fibronectin promotes rat Schwann cell growth and motility.J Cell Biol,1982,93(1):211-216.
30.Yuan Y,Zhang P,Yang Y,et al.The interaction of Schwann cells with chitosan membranes and fibers in vitro.Biomaterials,2004,25(18):4273-8.
31.Ciardelli G,Chiono V.Materials for peripheral nerve regeneration.Macromol Biosci,2006,6(1):13-26.
32.Young RC,Wiberg M,Terenghi G.Poly-3-hydroxybutyrate (PHB):a resorbable conduit for long-gap repair in peripheral nerves.Br J Plast Surg,2002,55(3):235-240.
1.顾立强,裴国献．周围神经损伤与临床[M]．北京,人民军医出版社,2001：100-101．
2.Bunge MB,Williams AK,Wood PM,et al.Comparison of nerve cell and nerve cell plus Schwann cell cultures,with particular emphasis on basal lamina and collagen formation.Cell Biol,1980,84(1):184-202.
3.Clark MB,Bunge MB.Cultured Schwann cells assemble normal-appearing basal lamina only when they ensheathe axons.Des Biol,1989,133(2):393-404.
4.Carey DG.Biosynthsis of type collagen by cultured rat Schwann cells.Cell Biol,1983,97(2):473-489.
5.Obremski VJ,Wood PM,Bunge MB.Fibroblasts promote Schwann cell basal lamina deposition and elongation in the absence of neurons in culture.Det Biol,1993,160(1):119-134.
6.Chemousov MA,Scherer SS,Stahl RC,et al.P200,a collagen secreted by Schwann cells,is expressed in developing nerves and in adult nerves following axotomy.J neurosci Res,1999,56(3):284-294.
7.Hirata K,Kawabuchi M.Myelin phagocytosis by macrophages and nonmacro-phages during Wallerian degeneration.Microsc Res Tech,2002,57(6):541-547.
8.La Fleur M,Underwood JL,Rappolee DA,el al.Basement membrane and repair of injury to peripheral nerve:defining a potential role for macrophages,matrix Metallo-proteinases,and tissue inhibitor of metalloproteinases-1.Exp Med,1996,184(6):2311-2326.
9.Martini R.Expression and functional roles of neural cell surface molecules and extracellular matrix components during development and regeneration of peripher-al Nerves.J Neurocytol,1994,23(1):1-28.
10.Pasterkamp RJ,Giger RJ.Regulation of semaphorin Ⅲ/ collapsing-1 gene expression during peripheral nerve regeneration.Exp Neurol,2001,153:313-327.
11.Rangappa N,Romero A,Nelson KD,et al.Laminin-coated poly(L-lactide) filaments induce robust neurite growth while providing directional orientation. Biomed Mater Res,2000,51 (4):625-634.
12.Colognato H,Yurchenco PD.Form and function:The laminin family of heterotri mers.Dev Dyn,2002,18:213-234.
13.Kuhn TB,Williams CV,Dou P,et al.Laminin direct s growth cone navigation via two temporally and functionally distinct calcium signals.Neurosci,1998,18:184-194.
14.Zu-Lin Chen,Sidney Strickland.Laminin-1 is critical for Schwann cell differ-enttiatio n,axon myelination,and regeneration in the peripheral nerve.The Journal of Cell Biology,2003,163(4):889-899.
15.Dubovy ZP,Svizenska I,Klusakova I,et al.Laminin molecules in freeze-treated nerve segments are associated with migrating Schwann cells that display the corresponding α6β1 integrin receptor.Glia,2001,33:36-44.
16.Baron-Van-Evercooren A,Kleinman HK,Seppa H E,el at.Fibronectin promotes rat Schwann cell growth and motility.J-Cell-Biol,1982,93(1):211-216.
17.Snow DM,Smit h JD,Cunningham AT,et al.Neurite elongation on chondroitin sulfate proteoglycans is characterized by axonal fasciculation.Exp Neurol,2003,182:310-321.
18.Fidler PS,Schuette K,Asher RA,et al.Comparing astrocytic cell lines that are inhibitory or permissive for axon growth:the major axon-inhibitory proteoglycan is NG2.Neurosc,1999,19:8778-8788.
19.Zuo J,Hernandez YJ,Muir D.Chondroitin sulfate proteoglycan with neurite inhibiting activity is upregulated following peripheral nerve injury.Neurobiol,1998,34:41-54.
20.Zuo J,Ferguson TA,Hernandez YJ,et al.Neuronal matrix metalloproteinase-2 degrades and inactivates a neurite-inhibiting chondroitin sulfate proteoglycan.Neurosci,1998,18:5203-5211.
21.Ferguson TA,Muir D.MMP-2 and MMP-9 increase the neuritepromoting potenti-al of Schwann cell basal laminae and are upregulated in degenerated nerve.Mol Cell Neurosci,2000,16:157-167.
22.Chafik D,Bear D,Bui P,et al.Optimization of Schwann cell adhesion in response to shear stress in an in vitro model for peripheral nerve tissue engineering.Tiss Eng,2003,9(2):233-241.
23.Obremski VJ,Wood PM,Bunge MB,et al.Fibroblasts promote Schwann cell basal lamina deposition and elongation in the absence of neurons in culture.D BioZ,1993,160(1):119-134.
24.王国英,秦建强.Laminin 等因子失活后巨噬细胞的行为对周围神经再生的影响.中华显微外科杂志,1995,18(1):30-33.
25.Verdu E,Labrador RO,Rodriguez FJ,et al.Alignment of collagen and laminin -containing gels improve nerve regeneration within silicone tubes.Restor Neurol Neurosci,2002,20(5):69-179.
26.郭义柱,卢世璧,王岩,等.去细胞同种异体神经移植修复人体长段周围神经缺损.中国临床康复,2005,38(9):26-27.
2.Sondell M,Lundborg G,Kanje M.Regeneration of the rat sciatic nerve into allografts made acellular through chemical extraction.Brain Res,1998,795:44-54.
3.衷鸿宾,卢世璧,赵庆,等.犬化学去细胞神经同种异体移植的神经再生研究.中华手外科杂志,2002,18:131-133.
4 衷鸿宾,卢世璧,赵庆,等.去细胞神经同种异体移植的运动功能恢复.中华创伤杂志,2002,18:533-535.
5.郭义柱,卢世璧,王岩,等.去细胞同种异体神经移植修复人体长段周围神经缺损.中国临床康复,2005,9(38):26-27.
6.Levi-Montalcini R,Skaper SD,Toso RD,et al.Nerve growth factor:from neurot -rophin to neurokine.Trends in Neurosci,1996,19(11):514-520.
7.Terenghi G.Peripheral nerve regeneration and neurotrophic factors.J Anatomy,1999,194:1-14.
8.Aloe L.Rita Levi-Montalcini:the discovery of nerve growth factor and modern neurobiology.Trends in Cell Biology,2004,14(7):395-399.
9.Gravvanis AI,Tsoutsos DA,Tagaris GA,et al.Beneficial effect of nerve growth factor-7S on peripheral nerve regeneration through inside-out vein grafts:An ex -perimental study.Microsurgery,2004,24(5):408-415.
10.Tsai CC,Lu MC,Chen YS,et al.Locally administered nerve growth factor supp -resses ginsenoside Rbl-enhanced peripheral nerve regeneration.Am J Chin Med,2003,31(5):665-673.
11.Camarata P J,Suryanarayanan R,Turner DA,et al.Sustained release of nerve growth factor from biodegradable polymer microspheres.Neurosurgery,1992,30(3):313-319.
12.Hadlock TA,Sheahan T,Cheney ML,et al.Biologic activity of nerve growth factor slowly released from microspheres.Biomaterials,2002,23(17):3765-3772.
13.Xiaoyun Xu,Harry Yu,Shujun Gao,et al.Polyphosphoester microshperes for sustained release of biologically active nerve growth factor.Biomaterials,2002, 23:3765-3722.
4.Xu X,Yee WC,Hwang PY,et al.Peripheral nerve regeneration with sustained release of poly(phosphoester) microencapsulated nerve growth factor within nerve guide conduits.Biomaterials,2003,24(13):2405-2412.
5.Jockenhoevel S,Zund G,Hoerstrup SP,et al.Fibrin gel-advantages of a new scaffold in cardiovascular tissue engineering.Eur J Cardiothorac Surg,2001,19(4):424-430.
6.Herbert CB,Bittner GD,Hubbell JA.Effects of fibinolysis on neurite growth from dorsal root ganglia cultured in two-and three-dimensional fibrin gels.J Comp Neurol,1996,365(3):380-391.
7.Lee AC,Yu VM,Lowe JB,et al.Controlled release of nerve growth factor enhances sciatic nerve regeneration.Exp Neurol,2003,184(1):295-303.
18.Previtali SC,Nodari A,Taveggia C,et al.Expression of laminin receptors in schwann cell differentiation:evidence for distinct roles.J Neurosci,2003,23(13):5520-5530.
19.Chen ZL,Strickland S.Laminin gammal is critical for Schwann cell differentia -tion,axon myelination,and regeneration in the peripheral nerve.J Cell Biol,2003,163(4):889-899.
20.Ferguson TA,Muir D.MMP-2 and MMP-9 increase the neurite-promoting poten -tial of Schwann cell basal laminae and are upregulated in degenerated nerve.Mol Cell Neurosci,2000,16(2):157-167.
21.Trigg D J,O'Grady KM,Bhattacharyya T,Reinke M,Toriumi DM.Peripheral nerve regeneration:comparison of laminin and acidic fibroblast growth factor.Am J Otolaryngol,1998,19(1):29-32.
22.Uziyel Y,Hall S,Cohen J.Influence of laminin-2 on Schwann cell-axon interacts -ions.Glia,2000,32(2):109-121.
23.王国英,平井圭一,钟世镇,等.雪旺氏细胞基底膜成分 laminin 在神经再生中的作用探讨.中国临床解剖杂志,1992,10(3):200-207.
24.Le Beau JM,Liuzzi FJ,Depto AS,et al.Up-regulation of laminin B2 gene expres -sion in dorsal root ganglion neurons and nonneuronal cells during sciatic nerve regeneration.Exp Neurol,1995,134(1):150-155.
25.Martini R.Expression and functional roles of neural cell surface molecules and extracellular matrix components during development and regeneration of peripheral nerves.J Neurocytol,1994,23(1):1-28.
26.Agius E,Cochard P.Comparison of neurite outgrowth induced by intact and injured sciatic nerves:a confocal and functional analysis.J Neurosci,1998,18(1):328-38.
27.Bovolenta P,Fernaud-Espinosa I.Nervous system proteoglycans as modulators of neurite outgrowth.Prog Neurobiol,2000,61(2):113-132.
28.Lander AD,Fujii DK,Reichardt LF.Purification of a factor that promotes neurite outgrowth:isolation of laminin and associated molecules.J Cell Biol,1985,101(3):898-913.
29.Okada N,Tanaka H,Takizawa H,et al.A monoclonal antibody that blocks the complement regulatory activity of guinea pig erythrocytes and characterization of the antigen involved as guinea pig decay-accelerating factor.J Immunol,1995,154(11):6103-6111.
30.Cole GJ,Loewy A,Glaser L.Neuronal cell-cell adhesion depends on interactions of N-CAM with heparin-like molecules.Nature,1986,320(6061):445-447.
31.Hantaz-Ambroise D,Vigny M,Koenig J.Heparan sulfate proteoglycan and lamin -in mediate two different types of neurite outgrowth.J Neurosci,1987,7(8):2293-2304.
32.Dou CL,Levine JM.Inhibition of neurite growth by the NG2 chondroitin sulfa -te proteoglycan.J Neurosci,1994,14(12):7616-7628.
33.Fidler PS,Schuette K,Asher RA,et al.Comparing astrocytic cell lines that are in -hibitory or permissive for axon growth:the major axon-inhibitory proteoglycan is NG2.J Neurosci,1999,19(20):8778-8788.
34.McKeon RJ,Hoke A,Silver J.Injury-induced proteoglycans inhibit the potential for laminin-mediated axon growth on astrocytic scars.Exp Neurol,1995,136(1):32-43.
35.Muir D,Engvall E,Varon S,Manthorpe M.Schwannoma cell-derived inhibitor of the neurite-promoting activity of laminin.J Cell Biol,1989,109(5):2353-62.
36.Schmalfeldt M,Bandtlow CE,Dours-Zimmermann MT,et al.Brain derived versi-can V2 is a potent inhibitor of axonal growth.J Cell Sci,2000,113:807-816.
37.Snow DM,Lemmon V,Carrino DA,e al.Sulfated proteoglycans in astroglial barriers inhibit neurite outgrowth in vitro.Exp Neurol,1990,109 (1):111-130.
38.Ughrin YM,Chen ZJ,Levine JM.Multiple regions of the NG2 proteoglycan inhibit neurite growth and induce growth cone collapse.J Neurosci,2003,23 (1):175-186.
39.Jones LL,Sajed D,Tuszynski MH.Axonal regeneration through regions of chon -droitin sulfate proteoglycan deposition after spinal cord injury:a balance of per-missiveness and inhibition.J Neurosci,2003,23(28):9276-9288.
40.Zuo J,Ferguson TA,Hernandez YJ,et al.Neuronal matrix metalloproteinase-2 degrades and inactivates a neurite-inhibiting chondroitin sulfate proteoglycan.J Neurosci,1998,18(14):5203-5211.
41.Baichwal RR,Bigbee JW,DeVries GH.Macrophage-mediated myelin-related mitogenic factor for cultured Schwann cells.Proc Natl Acad Sci USA,1988 85(5):1701-1705.
1.Dumont,CE,Hentz VR.Enhancement of axon growth by detergent-extracted nerve grafts.Transplantation,1997,63(9):1210-1215.
2.Sondell,MG,Lundborg,Kanje M.Regeneration of the rat sciatic nerve into allografts made acellular through chemical extraction.Brain Res,1998,795(1-2):44-54.
3.戴传昌,王炜,曹谊林,等.去细胞异体神经基膜管桥接神经缺损的实验研究.中华整形外科杂志,2001,17:366-368.
4.王建云.化学萃取同种异体神经种植许旺细胞的体外实验.中华显微外科杂志,2002,25:189-191.
5.Sun MX,Lu SB,Tang JS.Experimental study on repairing different length nerve defects with chemical extracted acellular nerve allograft.Orthopedic Journal of China,2006,14:603-607.
6.Verdu E,Labrador RO,Rodringuez F J,et al.Alignment of collagen and laminin-containing gels improve nerve regeneration within silicone tubes.Restor Neurol Neurosci,2002,20(5):169-79.
7.Dubovy P,Svizenska I,Klusakova I,et al.Laminin molecules in freeze-treated nerve segments are associated with migrating Schwann cells that display the corresponding alpha6betal integrin receptor.Glia,2001,33(1):36-44.
8.Fawcett JW,Keynes RJ.Peripheral nerve regeneration.Annu Rev Neurosci,1990,13:43-60.
9.Ide C,Osawa T,Tohyama K.Nerve regeneration through allogeneic nerve grafts,with special reference to the role of the Schwann cell basal lamina.Prog Neurobiol,1990,34(1):1-38.
10.Hudson TW,Liu SY,Schmidt CE.Engineering an improved acellular nerve graft via optimized chemical processing.Tissue Eng,2004,10(9-10):1346-58.
11.Hudson TW,Zawko S,Deister C,et al.Optimized acellular nerve graft is immunologically tolerated and supports regeneration.Tissue Eng,2004,10(11-12):1641-51.
12.Givogri MI,Bongarzone ER,Campagnoni AT.New insights on the biology of myelin basic protein gene:the neural-immune connection.J Neurosci Res,2000,59(2):153-9.
13.Lassner F,Schaller E,Steinhoff,et al.Cellular mechanisms of rejection and regeneration in peripheral nerve allografts.Transplantation,1989,48(3):386-92.
14.Mackinnon SE,Dellon AL.Clinical nerve reconstruction with a bioabsorbable polyglycolic acid tube.Plast Reconstr Surg,1990,85(3):419-24.
15.Meek MF,Den Dunnen WF,Schakenraad JM,et al.Long-term evaluation of functional nerve recovery after reconstruction with a thin-walled biodegradable poly(DL-lactide-epsilon-aprolactone) nerve guide,using walking track analysis and electrostimulation tests.Microsurgery,1999,19(5):247-53.
16.Li ST,Archibaid S J,Krarup C,et al.Peripheral nerve repair with collagen conduits.Clin Mater,1992,9(3-4):195-200.
17.Shaw D,Shoichet MS.Toward spinal cord injury repair strategies:peptide surface modification of expanded poly(tetrafluoroethylene) fibers for guided neurite outgrowth in vitro.J Craniofac Surg,2003,14(3):308-16.
18.Bozkurt A,Deumens R,Beckmann C,et al.In vitro cell alignment obtained with a Schwann cell enriched microstructured nerve guide with longitudinal guidance channels.Biomaterials,2009,30(2):169-79.
19.李立钧,陈统一.周围神经损伤与再生中的细胞和细胞因子.国外医学.骨科学分册,2004,25:280-283.
1.Levi-Montalcini R,Skaper SD,Toso RD,et al.Nerve growth factor:from neurot-rophin to neurokine.Trends in Neurosci,1996,19(11):514-520.
2.Xiaoyun Xu,Harry Yu,Shujun Gao,et al.Polyphosphoester microshperes for sustained release of biologically active nerve growth factor.Biomaterials,2002,23:3765-3722.
3.Terenghi G.Peripheral nerve regeneration and neurotrophic factors.J Anatomy,1999,194:1-14.
4.Aloe L.Rita Levi-Montalcini:the discovery of nerve growth factor and modern neurobiology.Trends in Cell Biology,2004,14(7):395-399.
5.Gravvanis Al,Tsoutsos DA,Tagaris GA,et al.Beneficial effect of nerve growth factor-7S on peripheral nerve regeneration through inside-out vein grafts:An experimental study.Microsurgery,2004,24(5):408-415.
6.Tsai CC,Lu MC,Chen YS,et al.Locally administered nerve growth factor suppresses ginsenoside Rb1-enhanced peripheral nerve regeneratioa Am J Chin Med,2003,31(5):665-673.
7.Xiaoyun Xua,Woon-Chee Yeeb,Peter YK,et al.Peripheral nerve regeneration with sustained release of poly(phosphoester) microencapsulated nerve growth factor within nerve guide conduits.Biomaterials,2003,24(13):2405-2412.
8.Bhang SH,Jeon O,Choi CY,et al.Controlled release of Nerve growth factor from fibrin gel.J Biomed Mater Res A,2007,80(4):998-1002.
9.Camarata PJ,Suryanarayanan R,Turner DA,et al.Sustained nerve growth factor from biodegradable polymer microsphere.Neurosurgery,1992,30(3):313-319.
1.徐杨,陈统一.周围神经修复方法进展.国外医学·骨科学分册,2004,25(5):270-274.
2.Sondell M,Lundborg G,Kanje M.Regeneration of the rat sciatic nerve into allografts made acellular through chemical extraction.Brain Res,1998,795(1-2):44-54.
3.Hudson TW,Liu SY,Schmidt CE.Engineering an improved acellular nerve graft via optimized chemical processing.Tissue Eng,2004,10(9-10):1346-1358.
4.Levi-Montalcini R,Skaper SD,Dal Toso R,et al.Nerve growth factor:from neurotrophin to neurokine.Trends Neurosci,1996,19(11):514-520.
5.王冠军,孙明学,卢世璧,等.改良化学去细胞同种异体神经制备方法的实验研究.中国矫形外科杂志,2007,15(12):929-932.
6.Lee AC,Yu VM,Lowe JB 3rd,et al.Controlled release of nerve growth factor enhances sciatic nerve regeneration.Exp Neurol,2003,184(1):295-303.
7.Xu X,Yee WC,Hwang PY,et al.Peripheral nerve regeneration with sustained release of poly(phosphoester) microencapsulated nerve growth factor within nerve guide conduits.Biomaterials,2003,24(13):2405-2412.
8.Zhu JY,Huang YT,Zhu QS,et al.Expression of adenovirus-mediated neurotrophin-3 gene in Schwann cells of sciatic nerve in rats.Chin J Traumatol,2003,6(2):75-80.
9.Aloe L.Rita Levi-Montalcini:the discovery of nerve growth factor and modern neurobiology.Trends Cell Biol,2004,14(7):395-399.
10.Gravvanis AI,Tsoutsos DA,Tagaris GA,et al.Beneficial effect of nerve growth factor-7S on peripheral nerve regeneration through inside-out vein grafts:an experimental study.Microsurgery,2004,24(5):408-415.
11.Tsai CC,Lu MC,Chen YS,et al.Locally administered nerve growth factor suppresses ginsenoside Rb1-enhanced peripheral nerve regeneration.Am J Chin Med,2003,31(5):665-673.
12.Kim BS,Yoo J J,Atala A.Peripheral nerve regeneration using acellular nerve grafts.J Biomed Mater Res A,2004,68(2):201-209.
13.孙明学,王鑫,赵斌,等.化学去细胞法对粗大神经质量评价方法及影响因素的探讨.中国修复重建外科杂志,2006,20(8):779-782.
14.Yoshimura K,Harii K.A regenerative change during muscle adaptation to denervation in rats.J Surg Res,1999,81(2):139-146.
15.赵磊,严志强,吕广明.失神经支配骨髂肌的萎缩机制.中国组织工程研究与临床康复,2007,11(6):1120-1122.
16.Lee DY,Choi BH,Park JH,et al.Nerve regeneration with the use of a poly(1-lactide-co-glycolic acid)-coated collagen tube filled with collagen gel.J Craniomaxillofac Surg,2006,34(1):50-56.
1.顾立强,裴国献．周围神经损伤与临床．人民军医出版社,2001：100-101．
2.Muir D,Engvall E,Varon S,et al.Schwannoma cell-derived inhibitor of the neurite-promoting activity of laminin.J Cell Biol,1989,109(5):2353-2362.
3.Snow DM,Lemmon V,Carrino DA,et al.Sulfated proteoglycans in astroglial barriers inhibit neurite outgrowth in vitro.Exp Neurol,1990,109(1):111-130.
4.Brittis PA,Canning DR,Silver J.Chondroitin sulfate as a regulator of neuronal patterning in the retina.Science,1992,255(5045):733-736.
5.McKeon RJ,Hoke A,Silver J.Injury-induced proteoglycans inhibit the potential for laminin-mediated axon growth on astrocytic scars.Exp Neurol,1995,136(1):32-43.
6.Friedman JA,Windebank AJ,Moore MJ,et al.Biodegradable polymer grafts for surgical repair of the injured spinal cord.Neurosurgery,2002,51(3):742-751.
7.Zuo J,Hernandez YJ,Muir D.Chondroitin sulfate proteoglycan with neurite-inhibiting activity is up-regulated following peripheral nerve injury.Journal of Neurobiology,1998 b,34(1):41-54.
8.Zuo J,Neubauer D,Dyess K,et al.Degradation of chondroitin sulfate proteoglycan enhances the neurite-promoting potential of spinal cord tissue.Exp Neurol,1998,154(2):654-662.
9.Bedi KS,Winter J,Berry M,et al.Adult Rat Dorsal Root Ganglion Neurons Extend Neurites on Predegenerated But Not on Normal Peripheral Nerves In Vitro.Eur J Neurosci,1992,4(3):193-200.
10.Agius E,Cochard P.Comparison of neurite outgrowth induced by intact and injured sciatic nerves:a confocal and functional analysis.J Neurosci,1998,18(1):328-338.
11.Danielsen N,Kerms JM,Holmquist B,et al.Pre-degenerated nerve grafts enhance regeneration by shortening the initial delay period.Brain Res,1994,666(2):250-254.
12.Chan YM,Wu W,Yip HK,et al.Caspase inhibitors promote the survival of avulsed spinal motoneurons in neonatal rats.Neuroreport,2001,12(3):541-545.
13.Hammarberg H,Piehl F,Risling M,et al.Differential regulation of trophic factor receptor mRNAs in spinal motoneurons after sciatic nerve transection and ventral root avulsion in the rat.J Comp Neurol,2000,426(4):587-601.
14.Shi TJ,Tandrup T,Bergman E,et al.Effect of peripheral nerve injury on dorsal root ganglion neurons in the C57 BL/6J mouse:marked changes both in cell numbers and neuropeptide expression.Neuroscience,2001,105(1):249-263.
15.Zuo J,Ferguson TA,Hernandez YJ,et al.Neuronal matrix metalloproteinase-2 degrades and inactivates a neurite-inhibiting chondroitin sulfate proteoglycan.Journal of Neuroscience,1998,18(14):5203-5211.
16.Zuo J,Neubauer D,Graham J,et al.Regeneration of axons after nerve transection repair is enhanced by degradation of chondroitin sulfate proteoglycan.Experimental Neurology,2002,176(1):221-228.
17.Hudson TW,Liu SY,Schmidt CE.Engineering an improved acellular nerve graft via optimized chemical processing.Tissue Eng,2004,10(9-10):1346-1358.
18.Hudson TW,Zawko S,Deister C,et al.Optimized acellular nerve graft is immunologically tolerated and supports regeneration.Tissue Eng,2004,10(11-12):1641-1651.
1.Dumont C E,Hentz VR.Enhancement of axon growth by detergent-extracted nerve grafts.Transplantation,1997,63(9):1210-5.
2.Sondell M,Lundbor G,Kanje M.Regeneration of the rat sciatic nerve into allografts made acellular through chemical extraction.Brain Res,1998,795(1-2):44-54.
3.Gulati AK.Evaluation of acellular and cellular nerve grafts in repair of rat peripheral nerve.J Neurosurg,1988,68(1):117-123.
4.Nadim W,Anderson PN,Turmaine M.The role of Schwann cells and basal lamina tubes in the regeneration of axons through long lengths of freeze-killed nerve grafts.Neuropathol Appl Neurobiol,1990,16(5):411-421.
5.Danielsen N,Kerms JM,Holmquist B,et al.Pre-degenerated nerve grafts enhance regeneration by shortening the initial delay period.Brain Res,1994,666(2):250-254.
6.Krekoski CA,Neubauer D,Graham JB,et al.Metalloproteinase-dependent predegeneration in vitro enhances axonal regeneration within acellular peripheral nerve grafts.J Neurosci,2002,22(23):10408-15.
7.Krekoski CA,Neubauer D,Zuo J,et al.Axonal regeneration into acellular nerve grafts is enhanced by degradation of chondroitin sulfate proteoglycan.Journal of Neuroscience,2001,21(16):6206-6213.
8.Jubran M,Widenfalk J.Repair of peripheral nerve transections with fibrin sealant containing neurotrophic factors.Exp Neurol,2003,181(2):204-212.
9.Fawcett JW,Keynes RJ.Peripheral nerve regeneration.Annu Rev Neurosci,1990,13:43-60.
10.Tohyama K,Ide C,Osawa T.Nerve regeneration through the cryo injured allogeneic nerve graft in the rabbit.Acta Neuropathol,1990,80(2):138-144.
11.Chong MS,Woolf CJ,Andrews P,et al.The downregulation of GAP-43 is not responsible for the failure of regeneration in freeze-killed nerve grafts in the rat.Exp Neurol,1994,129(2):311-20.
12.Ochi M,Wakasa M,Ikuta Y,et al.Nerve regeneration in predegenerated basal lamina graft:the effect of duration of predegeneration on axonal extension.Exp Neurol,1994,128(2):216-25.
13.Zuo J,Hernandez Y J,Muir D.Chondroitin sulfate proteoglycan with neuriteinhibiting activity is up-regulated following peripheral nerve injury.J Neurobiol,1998,34(1):41-54.
14.Ferguson TA,Muir D.MMP-2 and MMP-9 increase the neurite-promoting potential of schwann cell basal laminae and are upregulated in degenerated nerve.Mol Cell Neurosci,2000,16(2):157-167.
15.Muir D,Engvall E,Varon S,et al.Schwannoma cell-derived inhibitor of the neurite-promoting activity of laminin.J Cell Biol,1989,109(5):2353-2562.
16.Zuo J,Neubauer D,Dyess K,et al.Degradation of chondroitin sulfate proteoglycan enhances the neurite-promoting potential of spinal cord tissue.Exp Neurol,1998,154(2):654-662.
17.Yoshimura K,Harii K.A regenerative change during muscle adaptation to denervation in rats.J Surg Res,1999,81(2):139-46.
18.赵磊,严志强,吕广明.失神经支配骨骼肌的萎缩机制.中国组织工程研究与临床康复,2007,11(6):1120-1122.
1.Lundborg G.Alternatives to autologous nerve grafts.Handchir Mikrochir Plast Chir,2004,36(1):1-7.
2.Schmidt CE,Leach JB.Neural tissue engineering:strategies for repair and regeneration.Annu Rev Biomed Eng,2003,5:293-296.
3.Raimondo S,Nicolino S,Tos P,et al.Schwann cell behavior after nerve repair by means of tissue-engineered muscle-vein combined guides.J Comp Neurol,2005,489(2):249-259.
4.Hudson TW,Liu SY,Schmidt CE.Engineering an improved acellular nerve graft via optimized chemical processing.Tissue Eng,2004,10(9-10):1346-1358
5.Hudson TW,Evans GR,Schmidt CE.Engineering strategies for peripheral nerve repair.Clin Plast Surg,1999,26(4):617-628
6.张自杰,朱家恺.获得大量雪旺氏细胞的方法学研究.中华显微外科杂志,1992,15(2):87-89.
7.Patrick CW,Zheng B,Schmidt M,et al.Dermal fibroblasts genetically engineered to release NGF.Ann Plast Surg,2001,47(6):660-665.
8.Jimenez JC,Tyson DR,Dhar S,et al.Human embryonic kidney cells(HEK-293):characterization and dose response for modulated release of NGF for nerve regeneration.Plast Reconstr Surg,2004,113(2):605-610.
9.McConnell MP,Dhar S,Nguyen T,et al.Nerve growth factor expression response to induction agent booster dosing in transfected human embryonic kidney cells.Plast Reconstr Surg,2005,115(2):506-514.
10.McConnell MP,Dhar S,Naran S,et al.In vivo induction and delivery of nerve growth factor,using HEK-293 cells.Tissue Eng,2004,10(9-10):1492-501.
11.Knight MA,Evans GR.Tissue engineering:progress and challenges.Plast Reconstr Surg,2004,114(2):26E-37E.
12.Dezawa M.Future views and challenges to the peripheral nerve regeneration by cell based therapy.Rinsho Shinkeigaku,2005,45(11):877-879.
13.Murakami T,Fujimoto Y,Yasunaga Y,et al.Transplanted neuronal progenitor cells in a peripheral nerve gap promote nerve repair.Brain Res,2003,974(1-2):17-24.
14.Heine W,Conant K,Griffin JW,et al.Transplanted neural stem cells promote axonal regeneration through chronically denervated peripheral nerves.Exp Neurol, 2004,189(2):231-240.
15.Morrison SJ,White PM,Zock C,et al.Prospective identification,isolation by flow cytometry,and in vivo self renewal of multipotent mammalian neural crest stem cells.Cell,1999,96(5):737-749.
16.Tohill M,Terenghi G.Stem cell plasticity and therapy for injuries of the peripheral nervous system.Biotechnol Appl Biochem,2004,40(pt1):17-24.
17.Amoh Y,Li L,Campillo R,et al.Implanted hair follicle stem cells form Schwann cells that support repair of severed peripheral nerves.Proc Natl Acad Sci USA,2005,102(48):17734-17738.
18.Woodbury D,Schwarz EJ,Prockop DJ,et al.Adult rat and human bone marrow stromal cells differentiate into neurons.J Neurosci Res,2000,61(4):364-370.
19.Sanchez-Ramos J,Song S,Cardozo-Pelaez F,et al.Adult bone marrow stromal cells differentiate into neural cells in vitro.Exp Neurol,2000,164(2):247-56.
20.Akiyama Y,Radtke C,Kocsis JD.Remyelination of the rat spinal cord by transplantation of identified bone marrow stromal cells.J Neurosci,2002,22(15):6623-6630.
21.Dezawa M,Takahashi I,Esaki M,et al.Sciatic nerve regeneration in rats induced by transplantation of in vitro differentiated bone-marrow stromal cells.Eur J Neurosci,2001,14(11):1771-1776.
22.DiStefano PS,Friedman B,Radziejewski C,et al.The neurotrophins BDNF,NT-3,and NGF display distinct patterns of retrograde axonal transport in peripheral and central neurons.Neuron,1992,8(5):983-993.
23.Fu SY,Gordon T.The cellular and molecular basis of peripheral nerve regeneration.Mol Neurobiol,1997,14(1-2):67-116.
24.Bampton ET,Taylor JS.Effects of Schwann cell secreted factors on PC 12 cell neuritogenesis and survival.J Neurobiol,2005,63(1):29-48.
25.Gravel C,Gotz R,Lorrain A,et al.Adenoviral gene transfer of ciliary neurotrophic factor and brain-derived neurotrophic factor leads to long-term survival of axotomized moter neurons.Nat Med,1997,3(7):765-770.
26.Rangappa N,Romero A,Nelson KD,et al.Laminin-coated poly (L-lactide) filaments induce robust neurite growth while providing directional orientation.Biomed Mater Res,2000,51(4):625-634.
27.Colognato H,Yurchenco PD.Form and function:the laminin family of heterotrimers.Dev Dyn,2002,18(2):213-234.
28.Kuhn TB,Williams CV,Dou P,et al.Laminin directs growth cone navigation via two temporally and functionally distinct calcium signals.Neurosci,1998,18(1):184-194.
29.Baron-Van Evercooren A,Kleinman HK,Seppa HE,el at.Fibronectin promotes rat Schwann cell growth and motility.J Cell Biol,1982,93(1):211-216.
30.Yuan Y,Zhang P,Yang Y,et al.The interaction of Schwann cells with chitosan membranes and fibers in vitro.Biomaterials,2004,25(18):4273-8.
31.Ciardelli G,Chiono V.Materials for peripheral nerve regeneration.Macromol Biosci,2006,6(1):13-26.
32.Young RC,Wiberg M,Terenghi G.Poly-3-hydroxybutyrate (PHB):a resorbable conduit for long-gap repair in peripheral nerves.Br J Plast Surg,2002,55(3):235-240.
1.顾立强,裴国献．周围神经损伤与临床[M]．北京,人民军医出版社,2001：100-101．
2.Bunge MB,Williams AK,Wood PM,et al.Comparison of nerve cell and nerve cell plus Schwann cell cultures,with particular emphasis on basal lamina and collagen formation.Cell Biol,1980,84(1):184-202.
3.Clark MB,Bunge MB.Cultured Schwann cells assemble normal-appearing basal lamina only when they ensheathe axons.Des Biol,1989,133(2):393-404.
4.Carey DG.Biosynthsis of type collagen by cultured rat Schwann cells.Cell Biol,1983,97(2):473-489.
5.Obremski VJ,Wood PM,Bunge MB.Fibroblasts promote Schwann cell basal lamina deposition and elongation in the absence of neurons in culture.Det Biol,1993,160(1):119-134.
6.Chemousov MA,Scherer SS,Stahl RC,et al.P200,a collagen secreted by Schwann cells,is expressed in developing nerves and in adult nerves following axotomy.J neurosci Res,1999,56(3):284-294.
7.Hirata K,Kawabuchi M.Myelin phagocytosis by macrophages and nonmacro-phages during Wallerian degeneration.Microsc Res Tech,2002,57(6):541-547.
8.La Fleur M,Underwood JL,Rappolee DA,el al.Basement membrane and repair of injury to peripheral nerve:defining a potential role for macrophages,matrix Metallo-proteinases,and tissue inhibitor of metalloproteinases-1.Exp Med,1996,184(6):2311-2326.
9.Martini R.Expression and functional roles of neural cell surface molecules and extracellular matrix components during development and regeneration of peripher-al Nerves.J Neurocytol,1994,23(1):1-28.
10.Pasterkamp RJ,Giger RJ.Regulation of semaphorin Ⅲ/ collapsing-1 gene expression during peripheral nerve regeneration.Exp Neurol,2001,153:313-327.
11.Rangappa N,Romero A,Nelson KD,et al.Laminin-coated poly(L-lactide) filaments induce robust neurite growth while providing directional orientation. Biomed Mater Res,2000,51 (4):625-634.
12.Colognato H,Yurchenco PD.Form and function:The laminin family of heterotri mers.Dev Dyn,2002,18:213-234.
13.Kuhn TB,Williams CV,Dou P,et al.Laminin direct s growth cone navigation via two temporally and functionally distinct calcium signals.Neurosci,1998,18:184-194.
14.Zu-Lin Chen,Sidney Strickland.Laminin-1 is critical for Schwann cell differ-enttiatio n,axon myelination,and regeneration in the peripheral nerve.The Journal of Cell Biology,2003,163(4):889-899.
15.Dubovy ZP,Svizenska I,Klusakova I,et al.Laminin molecules in freeze-treated nerve segments are associated with migrating Schwann cells that display the corresponding α6β1 integrin receptor.Glia,2001,33:36-44.
16.Baron-Van-Evercooren A,Kleinman HK,Seppa H E,el at.Fibronectin promotes rat Schwann cell growth and motility.J-Cell-Biol,1982,93(1):211-216.
17.Snow DM,Smit h JD,Cunningham AT,et al.Neurite elongation on chondroitin sulfate proteoglycans is characterized by axonal fasciculation.Exp Neurol,2003,182:310-321.
18.Fidler PS,Schuette K,Asher RA,et al.Comparing astrocytic cell lines that are inhibitory or permissive for axon growth:the major axon-inhibitory proteoglycan is NG2.Neurosc,1999,19:8778-8788.
19.Zuo J,Hernandez YJ,Muir D.Chondroitin sulfate proteoglycan with neurite inhibiting activity is upregulated following peripheral nerve injury.Neurobiol,1998,34:41-54.
20.Zuo J,Ferguson TA,Hernandez YJ,et al.Neuronal matrix metalloproteinase-2 degrades and inactivates a neurite-inhibiting chondroitin sulfate proteoglycan.Neurosci,1998,18:5203-5211.
21.Ferguson TA,Muir D.MMP-2 and MMP-9 increase the neuritepromoting potenti-al of Schwann cell basal laminae and are upregulated in degenerated nerve.Mol Cell Neurosci,2000,16:157-167.
22.Chafik D,Bear D,Bui P,et al.Optimization of Schwann cell adhesion in response to shear stress in an in vitro model for peripheral nerve tissue engineering.Tiss Eng,2003,9(2):233-241.
23.Obremski VJ,Wood PM,Bunge MB,et al.Fibroblasts promote Schwann cell basal lamina deposition and elongation in the absence of neurons in culture.D BioZ,1993,160(1):119-134.
24.王国英,秦建强.Laminin 等因子失活后巨噬细胞的行为对周围神经再生的影响.中华显微外科杂志,1995,18(1):30-33.
25.Verdu E,Labrador RO,Rodriguez FJ,et al.Alignment of collagen and laminin -containing gels improve nerve regeneration within silicone tubes.Restor Neurol Neurosci,2002,20(5):69-179.
26.郭义柱,卢世璧,王岩,等.去细胞同种异体神经移植修复人体长段周围神经缺损.中国临床康复,2005,38(9):26-27.