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1.
背景:聚乳酸-羟基乙酸共聚物具有良好的生物相容性和可降解性性。 目的:制备载荷角质细胞生长因子聚乳酸-羟基乙酸共聚物控释载药系统用于组织工程皮肤。 方法:采用乳化-溶剂挥发法、冷冻干燥法制备载有角质细胞生长因子的聚乳酸-羟基乙酸共聚物纳米微球,并构建组织工程皮肤。扫描电镜、倒置显微镜、纳米粒度分析仪、紫外分光及ELISA法对微球评价其特性。 结果与结论:纳米微球载药量为(14.05±0.56)%,包封率为(59.86±2.38)%,角质细胞生长因子活性保留率(78.26±5.63)%,体外释放30 d的累积释药率达75%以上,微球形态规则圆润。微球形态规整,在脱细胞真皮表面分布均匀,与其联接良好。毛囊干细胞群在荷载聚乳酸-羟基乙酸共聚物纳米微囊脱细胞真皮上生长活跃,细胞形态良好,并呈克隆团生长。说明实验用组织工程材料制备工艺合理,材料相容性好,可用于构建新型组织工程皮肤。  相似文献   

2.
背景:骨组织工程骨构建中如何使生长因子持续高效发挥作用是影响成骨速度和质量的关键,现多以各种材料的微球或支架作为缓释载体,但缓释作用有待提高。 目的:实验拟制备壳聚糖微球,然后复合到纳米羟基磷灰石/聚乳酸-羟基乙酸支架上,形成双重缓释作用,并测量对牛血清白蛋白的释放效果。 方法:以牛血清白蛋白为模型药物,采用乳化交联法制备壳聚糖微球。将微球与纳米羟基磷灰石、聚乳酸-羟基乙酸按一定比例混合,以冰粒子为致孔剂,采用冷冻干燥法制备壳聚糖微球/纳米羟基磷灰石/聚乳酸-羟基乙酸复合支架。利用扫描电镜、激光粒度分析仪、压泵仪和力学性能测试仪检测复合支架的形态性能,考察药物在缓释支架上的体外释放规律。 结果与结论:所制备的壳聚糖微球形态良好,呈规则圆球形,粒径集中分布在20~40 μm,微球药物包封率为86.5%,载药量为0.8%,随牛血清白蛋白初始用量的增加,载药量可升高至2.6%,但包封率下降至74.1%。壳聚糖微球能均匀分布在聚乳酸-羟基乙酸支架上,形成壳聚糖微球/纳米羟基磷灰石/聚乳酸-羟基乙酸复合支架,孔径为100~400 μm,孔隙率> 80%,压缩强度为1.1~2.3 MPa,10周降解率为26.5%。单纯纳米羟基磷灰石/聚乳酸-羟基乙酸支架其牛血清白蛋白在36 h累积释放量达85%以上,壳聚糖微球其牛血清白蛋白10 d累积释放量为33.6%,复合支架其牛血清白蛋白40 d累积释放量为81.5%。结果证实包埋壳聚糖微球的纳米羟基磷灰石/聚乳酸-羟基乙酸支架其压缩强度和降解速率合适,对蛋白类药物具有良好的缓释作用,有望作为组织工程的支架材料和生长因子的缓释载体。 关键词:聚乳酸-羟基乙酸;支架;壳聚糖;缓释载体;骨修复材料,组织工程;生物材料 doi:10.3969/j.issn.1673-8225.2010.03.017  相似文献   

3.
背景:有实验表明聚羟基乙酸支架材料已成功在裸鼠及大型哺乳动物体内构建形成了组织工程化软骨、骨、肌腱等组织,将血管内皮细胞与平滑肌细胞接种于聚羟基乙酸能否在裸鼠皮下形成血管样结构? 目的:采用新生婴儿脐静脉血管内皮细胞与平滑肌细胞接种于片状聚羟基乙酸形成的复合物移植于裸鼠皮下,验证其形成血管样结构的可行性。 设计:对比观察。 单位:原上海第二医科大学组织工程重点实验室。 材料:实验于2002-01/06在上海第二医科大学组织工程重点实验室完成。新生婴儿脐带来源于本院妇产科健康新生儿,经产妇知情同意,实验经过医院伦理委员会的批准。选用26只3~4周龄清洁级裸鼠,雌雄不拘,实验过程中对动物的处置符合动物伦理学标准。聚羟基乙酸购自Albany International Research Co.。 方法:将体外培养、扩增的新生婴儿脐静脉血管内皮细胞与平滑肌细胞接种于片状聚羟基乙酸材料上,形成细胞-材料复合物,将该复合物包绕于硅胶管使成管状结构后移植于20只裸鼠皮下为实验组,将未接种细胞的单纯聚羟基乙酸置入其余6只裸鼠皮下。 主要观察指标:分别于细胞-生物材料复合物置入后第2,6周后取出两组移植物进行大体观察,并进行苏木精-伊红染色及免疫组织化学染色,检测VIII因子及α-平滑肌肌动蛋白的表达。 结果:裸鼠26只均进入结果分析。①大体观察结果:移植物置入2周后,两组移植物均有管状结构形成;置入6周后,对照组管形结构消失,围绕硅胶管有极薄的纤维组织包裹形成,抽去硅胶管后,纤维组织失去支撑,无法维持管型结构。实验组抽去硅胶管后,新生组织仍维持管型结构。②组织学观察及免疫组化检测结果:移植物置入2周后,两组均可在镜下观察到大量未完全降解的聚羟基乙酸,对照组内少有细胞成分,实验组内可见多量细胞存在;置入6周后,两组聚羟基乙酸成分基本消失,对照组只有菲薄的纤维结缔组织形成,实验组显示有新生血管组织形成,其最内层有VIII因子阳性细胞覆盖,管壁内有大量细胞外基质及散在的α-平滑肌肌动蛋白阳性细胞存在。 结论:血管内皮细胞、平滑肌细胞-聚羟基乙酸复合物置入裸鼠皮下可形成具有与正常血管组织学结构相似的血管。  相似文献   

4.
摘要 背景:Sox基因家族是一个新发现的基因家族,在胚胎发育、性别分化、神经系统及骨骼系统发育过程中起着重要的作用。 目的:观察SOX-9基因转染骨髓基质干细胞后在聚乳酸-羟基乙酸共聚物培养生长的生物相容性,以及其复合材料修复软骨缺损动物模型的可行性。 方法:将SOX-9基因转染成功后的骨髓基质细胞在聚乳酸-羟基乙酸共聚物培养生长,制备软骨缺损动物模型,将复合物植入软骨缺损,通过大体标本观察、组织学观察及Ⅱ型胶原免疫组织化学及RT-PCR检测对软骨缺损模型的修复效果。 结果与结论:SOX-9基因转染骨髓基质干细胞后可以在聚乳酸-羟基乙酸共聚物上正常生长,并有Ⅱ型胶原的高表达,将复合物植入软骨缺损后,可以修复软骨缺损动物模型。聚乳酸-羟基乙酸共聚物与转染后的骨髓基质细胞具有良好的生物相容性,可以修复兔软骨缺损动物模型。  相似文献   

5.
背景:眼镜蛇毒细胞毒素具有强烈的细胞毒活性,但缺乏特异性,全身用药可导致严重毒副作用,而采用缓释载体包载进行间质化疗可达到提高肿瘤局部治疗效应,并且减轻全身毒性。 目的:制备眼镜蛇毒细胞毒素-聚乳酸-羟基乙酸微球,观察其一般性质和体外释药特性。 设计、时间及地点:观察性实验,于2007-12/2008-05在福建医科大学医药生物工程中心完成。 材料:聚乳酸-羟基乙酸、聚乙烯醇由中国科学院成都有机化学有限公司提供,广东产中华眼镜蛇毒。 方法:采用分子筛、离子交换分离,反相疏水高效液相色谱方法纯化细胞毒素,MTT法检测细胞毒活性,复乳-溶剂挥发法制备载药微球。 主要观察指标:扫描电镜观察载药微球的表面形态,激光粒径仪测微球粒径,计算包封率、载药量、体外释放周期。 结果:纯化的眼镜蛇细胞毒素具有明显的细胞毒作用,对HepG2细胞12,24 h的IC50分别为1.43,1.12 mg/L。复乳法制备微球表面光滑圆整,粒径2~8 μm,包封率和载药率分别为(74.10±9.92)%和(0.72±0.09)%,21 d药物累积释放63.3%,释放细胞毒素保持较好的生物学活性。 结论:采用复乳-溶剂挥发法可制备具有较高包封率、良好缓释效果、保持完整生物学活性的眼镜蛇毒细胞毒素-聚乳酸-羟基乙酸微球。  相似文献   

6.
摘要 背景:目前临床使用的多烯紫杉醇注射液多采用吐温80作为增溶剂,容易导致过敏反应,且全身化疗不良反应大。采用聚乳酸-羟基乙酸包载多烯紫杉醇制备的缓释微球进行肿瘤间质化疗可提高肿瘤局部药物浓度,减轻全身不良反应。 目的:制备一种用于肿瘤间质化疗的载多烯紫杉醇聚乳酸-羟基乙酸缓释微球,并考察其理化性质、体外释放及药物稳定性。 方法:采用溶剂挥发法制备不同投料比载药微球,扫描电镜观察微球的表面形态、粒径,高效液相色谱法检测包封率、载药率及体外药物释放情况。将制备的微球于5,15,25 kGy 60Co 3种剂量辐照灭菌,体外细菌培养观察灭菌效果。 结果与结论:制备的载药微球呈圆球形,表面光滑,分散良好,平均粒径为23.1 µm。聚乳酸-羟基乙酸与多烯紫杉醇的投料比为100 mg/5 mg时可获得最佳的包封率(96.3%)和载药率(4.82%);载药微球体外4周平稳释放药物达81.6%,无明显突释效应,包裹在微球内的多烯紫杉醇结构稳定性明显提高;3种剂量60Co辐照后均未见短小芽孢杆菌生长。说明采用溶剂挥发法可制备粒径及分布适宜、释放周期较理想、药物稳定性好的载多烯紫杉醇聚乳酸-羟基乙酸缓释微球。 关键词:多烯紫杉醇;聚乳酸-羟基乙酸;微球;缓释;生物材料与药物控释 doi:10.3969/j.issn.1673-8225.2010.21.013  相似文献   

7.
用于制备乳酸-羟基乙酸共聚物缓释微球的方法很多,可根据聚合物和药物的性质进行选择,其中乳化-固化法是目前制备乳酸-羟基乙酸共聚物缓释微球中最常用的方法,适用于在连续相中不溶或难溶的药物,缺点在于使用有机溶剂,不利于保持药物的活性,复乳化时工艺也比较复杂,不适宜进行工业化生产;喷雾干燥技术是一种快速的一步微囊化过程,其条件温和,制得的微球具有粒度分布窄、包封率高等特点,其用于不稳定药物微囊化的大规模生产极具潜力。由于给药初期的突释有可能导致血药浓度接近或超过中毒水平,产生明显的毒副作用。乳酸-羟基乙酸共聚物的分子质量、乳酸-羟基乙酸共聚物的纯度、主药理化性质、微球制备方法及制备参数、微球载药量等均是影响突释程度的具体因素。目前防止突释或降低突释程度的方法主要有改变载体材料结构、适当的微球制备以及萃取、洗涤或加入附加剂等。乳酸-羟基乙酸共聚物微球控释系统具有延长药物释放时间、靶向释放、降低药物毒性和刺激性等特点,存在多种给药途径可肌肉注射、皮下注射、玻璃体内注射、关节腔内给药、植入给药、黏膜给药等。  相似文献   

8.
背景:以往有很多学者通过发泡法将β-磷酸三钙与明胶复合得到引导组织再生材料,但将其采用静电纺丝技术制成纤维膜的报道很少。 目的:制备新型引导组织再生膜,并比较其与聚乳酸,聚丙交酯/乙交酯膜的细胞毒性。 方法:采用静电纺丝法制备β-磷酸三钙/明胶引导组织再生膜,通过扫描电子显微镜对纤维膜表面进行观察。通过MTT实验对电纺β-磷酸三钙/明胶膜与聚乳酸,聚丙交酯/乙交酯膜的细胞毒性进行对比。 结果与结论:新型电纺β-磷酸三钙/明胶膜为多孔状,β-磷酸三钙颗粒呈结节状附着在明胶纤维表面,纤维直径平均为400~500 nm,分布比较集中,大多在200~500 nm之间。与聚乳酸,聚丙交酯/乙交酯膜及阴性对照之间细胞毒性差异无显著性意义(P > 0.05)。说明新型电纺β-磷酸三钙/明胶引导组织再生膜细胞毒性较低,基本符合生物材料安全性的要求,有望成为新型的引导组织再生膜材料之一。 关键词:明胶;β-磷酸三钙;聚乳酸;聚丙交酯/乙交酯;引导组织再生;静电纺丝;生物相容性 doi:10.3969/j.issn.1673-8225.2010.16.014  相似文献   

9.
While peripheral nerves demonstrate the capacity for axonal regeneration, outcome following injury remains relatively poor, especially following prolonged denervation. Since axon-deprived Schwann cells (SCs) in the distal nerve progressively lose their ability to support axonal growth, we took the approach of using skin-derived precursor cells (SKPs) as an accessible source of replacement SCs that could be transplanted into chronically denervated peripheral nerve. In this study, we employed a delayed cross-reinnervation paradigm to assess regeneration of common peroneal nerve axons into the chronically denervated rodent tibial nerve following delivery of SKP-derived SC (SKP-SCs). SKP-SC treated animals exhibited superior axonal regeneration to media controls, with significantly higher counts of regenerated motorneurons and histological recovery similar to that of immediately repaired nerve. Improved axonal regeneration correlated with superior muscle reinnervation, as measured by compound muscle action potentials and wet muscle weights. We therefore conclude that SKPs represent an easily accessible, autologous source of stem cell-derived Schwann cells that show promise in improving regeneration through chronically injured nerves.  相似文献   

10.
Antegrade, target-directed axonal regeneration is the explicit goal of nerve repair. However, aberrant and dysfunctional regrowth is commonly observed as well. At the site of surgical nerve coaptation, axonal sprouts encounter fibrotic connective tissue rich in growth-inhibiting chondroitin sulfate proteoglycan that may contribute to misdirection of axonal regrowth. In the present study, we tested the hypothesis that degradation of chondroitin sulfate proteoglycan by application of chondroitinase at the site of nerve repair can decrease aberrant axonal growth. Adult rats received bilateral sciatic nerve transection and end-to-end repair. One nerve was injected with chondroitinase ABC and the contralateral nerve treated with vehicle alone. After 28 weeks, retrograde axonal regeneration was assessed proximal to the repair by scoring neurofilament-immunopositive axons within the nerve (intrafascicular) and outside the nerve proper (extrafascicular). Intrafascicular retrograde axonal growth was equivalent in both control and chondroitinase treatment conditions. In contrast, chondroitinase treatment caused a pronounced (93%) reduction in extrafascicular retrograde axonal growth. The decrease in axon egress from the nerve was coincident with an increase in antegrade regeneration and improved recovery of motor function. Based on these findings, we conclude that chondroitinase applied at the site of nerve transection repair averts dysfunctional extrafascicular retrograde axonal growth.  相似文献   

11.
Mesenchymal stem cells (MSCs) support axon regeneration across artificial nerve bridges but their differentiative capacity and ability to promote nerve regeneration remains unclear. In this study, MSCs isolated from bone marrow of Sprague–Dawley rats were characterized by plastic adherence and pluripotency towards mesodermal lineages. Isolated undifferentiated MSCs (uMSCs) were stimulated towards a Schwann cell (SC) phenotype using specific growth factors, and cell marker analysis was performed to verify SC phenotype in vitro. Differentiation resulted in temporally dependent positive immunocytochemical staining for the SC markers, glial fibrillary acidic protein (GFAP), S100, and nerve growth factor receptor (NGFR), with maximal marker expression achieved after 6 days of treatment with differentiation media. Quantitative analysis demonstrated that ~ 50% of differentiated MSCs (dMSCs) have a SC phenotype. Using an indirect co-culture system, we compared the ability of dorsal root ganglion (DRG) cells to extend neurites in indirect contact with uMSCs and dMSCs as compared to SCs. The mean values of the longest length of the DRG neurites were the same for the dMSCs and SCs and significantly higher than the uMSC and DRG mono-culture systems (p < 0.05). In vivo, compared to an empty conduit, dMSC seeded collagen nerve conduits resulted in a greater number of sciatic motoneurons regenerating axons through the conduit into the distal nerve stump. We conclude that bone marrow-derived MSCs differentiate into a SC-phenotype that expresses SC markers transiently and sufficiently to support limited neurite outgrowth in vitro and axonal regeneration equivalent to that of SCs in vitro and in vivo. The nerve autograft remains the most effective conduit for supporting regeneration across nerve gaps.  相似文献   

12.
目的 应用含有神经生长因子(NGF)的壳聚糖神经导引管作为神经再生室桥接大鼠坐骨神经缺损,观察其对神经再生的作用。方法 选用Wistat大鼠60只,手术造成右后肢坐骨神经长约15mm的缺损,A组以含有NGF的壳聚糖神经导引管桥接神经缺损,B组则单纯采用壳聚糖导管,分别于术后4、12、24周进行大体及显微解剖观察、组织学检查、电镜观察和神经电生理测定。结果 A组在促进神经再生、加快血管化进程、再生神经纤维排列规律化、提高再生神经髓鞘化、加速再生神经功能重建等方面均优于B组。结论 壳聚糖神经导引管可以为大鼠坐骨神经再生提供一个良好的再生微环境,NGF对神经再生有显促进作用。  相似文献   

13.
The pseudo-nerve, which contains longitudinal Schwann cell columns without axons and surrounded by perineurium-like tissue but no axons (Q. Zhao, L.B. Dahlin, M. Kanje, G. Lundborg, Brain Res. 592 (1992) 106–114), was applied as a graft to repair nerve defect in rats. Creation of the pseudo-nerve was accomplished by inserting the proximal and distal stumps of a cut sciatic nerve into a silicone tube. The proximal insert was cut far proximally to prevent axons from entering the tube. After 4 weeks, the pseudo-nerve was harvested, trimmed into a 10-mm long graft and transplanted into a corresponding defect of the contralateral sciatic nerve. Nerve regeneration through the pseudo-nerve was examined by pinch reflex test and neurofilament staining after 6 days or by morphology after 4, 6 or 8 weeks. The results showed that the pseudo-nerve could induce nerve regeneration to a similar extend as a real nerve graft. The neurobiological composition of the pseudo-nerve and the factors influencing its formation were also studied. By double staining of S-100 and laminin we found that the longitudinally organized Schwann cell columns in the pseudo-nerve were surrounded by basal laminae and ensheathed by a layer of vascularized perineurium-like tissue. Macrophages (ED1 and ED2) and their products interleukin-1β (IL-1β) and transforming growth factor-β1 (TGF-β1) were constantly present in the pseudo-nerve. Besides, the size of tube was a crucial factor in influencing pseudo-nerve formation, e.g. a thicker pseudo-nerve was formed in tubes with larger diameters or shorter gap lengths. No pseudo-nerve was formed when the gap was 15 mm long. When both proximal and distal inserts were isolated nerve segments the pseudo-nerve was still formed but thin, probably because of compromised vascular supply. Taken together, the results suggested that the pseudo-nerve contains the essential neurobiological elements to induce successful axonal elongation.  相似文献   

14.
Li Z  Peng J  Wang G  Yang Q  Yu H  Guo Q  Wang A  Zhao B  Lu S 《Experimental neurology》2008,214(1):47-54
Options for reconstructing peripheral nerve gaps after trauma are limited. The acellular nerve is a new kind of biomaterial used to reconstruct the peripheral nerve defect, but its use could be improved upon. We aimed to investigate the effect of adenoviral transfection with hepatocyte growth factor (HGF) on the functional recovery of transected sciatic nerves repaired by acellular nerve grafting. 30 Rats were divided into three groups (10/group) for autografting and acellular grafting, as well as acellular grafting with adenovirus transfection of HGF (1 × 108 pfu) injected in muscles around the proximal and distal allograft coapation. Sciatic functional index (SFI) was evaluated every 4 weeks to week 16 by measuring rat footprints on walking-track testing. The three groups presented initial complete functional loss, followed by slow but steady recovery, with final similar SFIs. Weight of the gastrocnemius and soleus muscles, histologic and morphometric study and neovascularization in the nerve grafts were evaluated at week 16. Autografting gave the best functional recovery, but HGF-treated acellular grafting gave better recovery than acellular grafting alone. Neovascularization was greater with HGF-treated acellular grafting than with autografting and acellular grafting alone. Axonal regeneration distance of autografting on the 20th postoperative day was the longest in the three groups,while that of acellular grafting alone was the smallest. Acellular nerve grafting may be useful for functional peripheral nerve regeneration, and with human HGF gene transfection may improve on acellular grafting alone in functional recovery.  相似文献   

15.
神经桥接与导管套接修复猫动眼神经形态学观察   总被引:6,自引:1,他引:5  
目的探求导管修复颅内段动眼神经的可行性.方法 20只健康家猫随机分为2组.将右侧动眼神经于脑池段切断后,分组采用自体神经桥接和导管套接的方法修复.术后14周末光镜、电镜观察神经纤维的连续性、再生纤维数目和直径.结果神经修复14周后,神经桥接组67%、导管套接组75%的动物其动眼神经功能均有一定程度的恢复.形态学显示两组均取得较好的神经再生效果,两组间再生纤维直径差异无显著性(P>0.05),但导管套接组再生神经纤维数目较多,差异有显著性(P<0.05).结论导管套接法可作为颅内段动眼神经损伤后的一种修复方法,其疗效近似或稍优于神经桥接法.  相似文献   

16.
Summary A wound chamber model was used for the study of the interaction between axon, Schwann cell and extracellular matrix during peripheral nerve regeneration. Impermeable silicone tubes, 8 mm long and 1.4 mm in internal diameter were sutured to transected rat sciatic nerve and the contents of the tubes were removed at intervals for chemical, histological, immunocytochemical and electron microscopic studies. There was an initial phase of fluid accumulation and the formation of a fibrin/fibronectin clot or cable which connected the cut ends of the nerve. The chamber fluid was shown to have a protein profile similar to that of rat serum. Schwann cells, endothelial cells and fibroblasts migrated first into the cable, apparently mediated by cell-fibrin interaction. Axons buried within the Schwann cell cytoplasm were led into the cable but an axon-fibrin interaction was not observed. After 1 week, the fibrin matrix underwent dissolution, with replacement by collagen. This marked the onset of myelination and the organization of nerve fibers into fascicles. The findings from the present study suggest that the interactions between axon and Schwann cell and between Schwann cell and a changing extracellular matrix are the essential driving force in nerve growth and differentiation during peripheral nerve regeneration.Supported by a grant from the National Science Council of R. O. C. (NSC 80-0412-B075-67)  相似文献   

17.
组织工程周围神经修复坐骨神经缺损应用研究   总被引:3,自引:0,他引:3  
目的应用组织工程方法构建周围神经以修复坐骨神经缺损.方法体外培养的雪旺细胞(SC)与牛去细胞基质(BAM)、胎牛血清和培养液按一定的比例混合注入聚乳酸聚羟基己酸共聚物(PLGA)导管中,构建成组织工程周围神经.30只SD大鼠随机分为3组,实验组:使用组织工程周围神经修复坐骨神经缺损;对照组:用不含雪旺细胞的导管修复;自体神经组:自体神经移植.16周后通过免疫组化、电生理、透射电镜、辣根过氧化物酶(HRP)逆行示踪及坐骨神经功能指数(SFI)等方法检测神经再生及坐骨神经功能恢复情况.结果 PLGA导管至16周已基本吸收,再生神经已通过缺损区长至远端,组织工程周围神经的修复效果接近自体神经组,优于空白组.结论体外构建的组织工程周围神经可以修复周围神经缺损.  相似文献   

18.
The effects of nerve predegeneration on the preferential growth of regenerating axons were studied using a silicone Y-chamber model. This system provided a choice for axons to grow towards two distal nerve options, either a 7-day predegenerated nerve segment (PNS) or a fresh nerve segment (FNS). The rat peroneal or tibial nerve was inserted into the proximal intlet and the PNS and FNS of the corresponding nerve were inserted into the distal outlets. At 28 days postoperative, the size of the distal regenerate was significantly greater (26%) towards the PNS for the tibial nerve group. The density and number of regenerated myelinated axons in the distal nerve segment was greater on the PNS for both the tibial (97 and 88%, respectively) and peroneal (221 and 221%, respectively) nerve groups. In contrast, the elevated density and number of nonvascular nuclei was relatively constant for both PNS and FNS. Immunocytochemical and ultrastructural evidence support the hypothesis that the early activation of Schwann cells is primarily responsible for the enhanced regeneration and maturation observed in PNS. It is suggested that PNS might improve the outcome after clinical repair of injured peripheral nerves.  相似文献   

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