静电纺丝聚乳酸聚乙醇酸共聚物-丝素-胶原神经导管修复大鼠周围神经缺损

背景:周围神经缺损修复是临床上一大难题,由于自体神经移植有一定的局限性,人工神经修复材料是一种很有前途的选择.目的:探讨静电纺丝聚乳酸聚乙醇酸共聚物(PLGA)-丝素-胶原纳米神经导管修复大鼠坐骨神经缺损的可能性.方法:雌性SD大鼠36只,制备约10 mm的坐骨神经缺损,分别采用倒转自体神经、静电纺丝PLGA-丝素-胶原神经导管、单纯 PLGA 神经导管桥接,术后12周进行大体观察、神经电生理测定、光镜观察、透射电镜观察和图像分析对比,了解神经再生的情况.结果与结论:静电纺丝法制备成的纳米神经导管管壁疏松多孔,能够模拟细胞外基质的结构.静电纺丝 PLGA-丝素-胶原神经导管组在促进坐骨神经再生、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单纯 PLGA导管组,比自体神经移植组略差.     

复合他克莫司聚乳酸-乙醇酸缓释导管修复大鼠胫神经缺损

背景：虽然单纯聚乳酸-乙醇酸导管修复大鼠神经缺损可部分恢复大鼠神经功能,但神经直径、再生纤维数量、髓鞘成熟度及功能恢复上均较自体神经移植差。目的：观察复合他克莫司的聚乳酸-乙醇酸缓释导管修复大鼠胫神经缺损的可行性。方法：制作SD大鼠右侧胫神经缺损模型,随机分为3组,分别植入自体胫神经、单纯聚乳酸-乙醇酸导管及复合他克莫司的聚乳酸-乙醇酸缓释导管修复。植入后3,6,12周行坐骨神经功能指数检查、电生理检查、组织学观测、腓肠肌湿质量测量。结果与结论：植入后第6,12周复合他克莫司的聚乳酸-乙醇酸缓释导管组、自体胫神经组坐骨神经功能指数检查、电生理检查、组织学观测、腓肠肌湿质量测量结果优于单纯聚乳酸-乙醇酸导管组（P〈0.05）,自体胫神经组、复合他克莫司的聚乳酸-乙醇酸缓释导管组比较差异无显著性意义。说明复合他克莫司的聚乳酸-乙醇酸缓释导管桥接修复大鼠胫神经缺损可明显促进断端神经的再生,在晚期功能恢复上取得接近自体神经移植的效果。     

无细胞神经支架复合骨髓间充质干细胞构建组织工程人工神经修复坐骨神经缺损

背景：作者已经成功制备了无细胞神经移植物,并且复合骨髓间充质干细胞构建组织工程人工神经桥接大鼠坐骨神经缺损。目的：无细胞神经移植物复合骨髓间充质干细胞构建组织工程人工神经修复大鼠坐骨神经缺损后运动功能的恢复。方法：成年雄性SD大鼠构建大鼠坐骨神经15mm缺损模型,分别应用组织工程人工神经、组织工程神经支架或自行神经桥接坐骨神经缺损。桥接后20周再生神经电生理学测定,手术侧胫骨前肌湿质量、腓肠肌组织学及透视电镜分析。结果与结论：桥接20周后,组织工程人工神经与自体神经移植组胫骨前肌湿质量比较,差异无显著性意义（P〉0.05）,神经干传导速度为（30.56±2.15）m/s。结果提示,无细胞神经移植物复合骨髓间充质干细胞构建的组织工程人工神经桥接大鼠坐骨神经缺损后,可以促进再生神经运动功能的恢复。     

无细胞神经移植物复合骨髓间充质干细胞构建组织工程人工神经修复坐骨神经缺损

背景:作者前期已经成功将无细胞神经移植物复合骨髓间充质干细胞构建组织工程人工神经,并证明可以促进周围神经再生.目的:构建组织工程人工神经,观察和验证桥接大鼠坐骨神经缺损后的神经功能恢复情况.方法:成年雄性SD大鼠60只构建大鼠坐骨神经15 mm缺损模型.随机分成3组,每组20只.桥接大鼠坐骨神经缺损,实验组采用组织工程人工神经,空白对照组采用无细胞组织工程神经支架,自体神经对照组采用自体神经移植.桥接后12周通过大体观察、胫骨前肌湿质量、组织学等方法分析坐骨神经组织学及功能恢复情况.结果与结论:桥接术后12周:实验组大鼠肢体可以支撑着地,钳夹大鼠手术侧足底皮肤出现逃避反射,足底皮肤s.100蛋白染色呈阳性反应.实验组与自体神经移植组胫骨前肌湿质量比差异无显著性意义(P＞0.05).实验组辣根过氧化物酶逆行示踪实验显示脊髓、后根神经节均可见数量不等的辣根过氧化物酶标记阳性细胞.实验组移植物与自体神经移植组有髓神经纤维数、髓鞘厚度、神经组织面积比较差异无显著性意义.实验结果验证了无细胞神经移植物复合骨髓间充质干细胞构建组织工程人工神经修复大鼠坐骨神经缺损,可以促进神经组织学的修复重建和功能的恢复.     

神经导管结合神经片段修复外周神经损伤

目的研究神经片段结合神经导管治疗外周神经缺损,为周围神经损伤修复与重建的解决途径提供实验依据。方法 24只成年Wistar大鼠随机分为A、B、C组,分别为神经自体移植、与含有神经片段的神经导管和单纯导管移植桥接大鼠10mm神经缺损,各组间在形态学、电生理、组织学进行比较。结果 B组大鼠移植侧肢体足迹实验的坐骨神经功能指数(SFI)为-81.20±2.81,神经干传导速度为(28.93±5.07)m/s、动作电位的振幅为(5.46±2.76)mV,再生神经中段检查髓鞘化轴突密度为(3953±468)/视野,髓鞘面积为(2.77±0.83)μm,与C组比较差异有统计学意义(P<0.05)。结论含有神经片段的神经导管组织工程移植体桥接神经缺损有促进神经轴突再生与神经功能恢复的良好作用,效果优于单纯神经导管移植。     

壳聚糖导管结合碱性成纤维细胞生长因子修复大鼠坐骨神经缺损

目的:应用含有碱性成纤维细胞生长因子的壳聚糖神经导管桥接大鼠坐骨神经缺损,观察其对神经再生的作用。方法:实验于2004-09/2005-05在辽宁医学院附属第一医院外科实验室完成。选择健康成年SD大鼠30只,按随机数字表法分为3组,复合导管组、自体神经移植组和单纯导管组,每组10只。分别采用壳聚糖加碱性成纤维细胞生长因子复合导管,自体神经移植和壳聚糖导管加生理盐水的单纯导管修复大鼠右后肢坐骨神经约10mm的缺损。术后4个月进行形态学(光镜、透射电镜、免疫组织化学、轴突图像分析)和神经电生理学(运动神经传导速度、复合肌肉动作电位)检测。结果:纳入大鼠30只,均进入结果分析。①术后4个月复合导管组各项指标与自体神经移植组相当,明显好于单纯导管组,400倍视野下,复合导管组再生神经的数目多于单纯导管组、直径(像素值)大于单纯导管组,差异有非常显著性意义[分别为(523.3±53.1),(452.2±32.1);45.63±4.61,36.36±3.51,F=15.56,37.76,P<0.01]。②透射电镜显示复合导管组再生神经纤维直径、轴突粗细、髓鞘厚度及形态学方面更接近自体神经移植组,而明显优于单纯导管组。③S-100蛋白免疫组织化学染色结果表明复合导管组有大量雪旺细胞增生,其数量和排列上达到自体神经移植水平。④电生理指标:复合导管组坐骨神经平均传导速度低于自体神经移植组,但高于单纯导管组,差异有显著性意义[分别为(17.53±2.76),(21.96±2.73),(14.37±2.43)m/s,F=5.528,P<0.05]。复合导管组复合肌肉动作电位接近于自体神经移植组,高于单纯导管组,差异有显著性意义[分别为(14.45±3.13),(15.62±3.40),(10.63±2.29)mV,F=9.905,P<0.01]。结论:壳聚糖加碱性成纤维细胞生长因子神经导管可以为神经修复提供一个良好的微环境,并显著促进神经的再生。     

神经再生室桥接断离面神经的实验研究

目的 探索面神经断离后临床治疗方法，探讨经自体筋膜神经再生室加神经生长因子（NGF）桥接神经的效果。方法 24只雄兔，按术式随机分组。A组：应用神经再生室＋无细胞肌基膜管；B组：应用神经再生室内置无细胞肌基膜管和NGF；C组：自体神经原位修复为对照组；分别桥接8mm缺损，术后24周，应用神经电生理、HE染色、秀射电镜及图象分析仪检测神经再生效果。结果 B组再生神经与对照组相似（P&;gt;0.05），再生神经以有髓终结为主，髓鞘较厚；A组再生神经数量、髓鞘厚度等指标与B、C组之间有显著性差异（P&;lt;0.05）。结论 自体筋膜做成神经再生室内置无细胞肌基膜管内NGF可有效地引导神经再生并修复断离面神经，该方法有临床应用价值。     

辣根过氧化物酶逆行示踪评价无细胞神经移植物复合骨髓间充质干细胞对坐骨神经缺损大鼠运动神经元的作用

背景:作者前期将无细胞神经移植物与骨髓间充质干细胞复合培养,成功构建了组织工程人工神经.目的:应用辣根过氧化物酶(HRP)神经逆行示踪技术对无细胞神经移植物复合骨髓间充质干细胞构建的神经移植复合体桥接大鼠坐骨神经缺损后运动冲经元的保护作用进行评价.方法:成年清洁级健康雄性SD大鼠,随机分成3组:①实验组:采用复合骨髓问充质干细胞的无细胞神经移植物桥接大鼠坐骨神经缺损.②空白对照组:采用无细胞神经移植物桥接大鼠坐骨神经缺损.⑨自体神经对照组:采用自体神经移植桥接大鼠坐骨神经缺损.术后12刷应用辣根过氧化物酶神经逆行示踪技术对脊髓前角运动神经元的再牛进行评价.结果与结论:术后12周脊髓前角运动神经元再生评价结果显示:实验组优丁无细胞神经移植物组,而与自体神经移植物组相比差异无显著性意义.证实无细胞神经移植物复合骨髓间充质干细胞构建组织工程人工神经修复人鼠坐骨神经缺损,对大鼠脊髓运动神经元具有倨护作用,可能达到与自体神经移植相似的效果.     

复合许旺细胞的猪肠黏膜下层桥接修复周围神经缺损

背景：小肠黏膜下层作为一种天然的生物材料,能提供适合神经生长的三维支架,而许旺细胞又在神经再生过程中发挥重要作用。如果能将许旺细胞种植在小肠黏膜下层,用来桥接周围神经缺损,理论上更有利于神经的长入,极有可能获得良好的实验效果。目的：应用复合有许旺细胞的小肠黏膜下层桥接周围神经缺损,观察桥接后神经生长情况。设计、时间及地点：对比观察实验,于2008-01在深圳市松岗人民医院完成。材料：取健康成年猪的新鲜近段空肠制备小肠黏膜下层。方法：SD大鼠20只随机分成2组,即复合有许旺细胞的小肠黏膜下层桥接组、自体神经移植组。每组10只。首先在距坐骨神经出口1cm处用双面刀片切取1cm长度的坐骨神经,造成神经缺损模型。然后分别用复合有许旺细胞的小肠黏膜下层桥接、自体神经移植桥接。主要观察指标：于术后6,12周自近端缝合口的近端至远端缝合口的远端切取大鼠的坐骨神经,用于病理组织学观察并进行图像分析。同时用生理示波器测定大鼠两侧坐骨神经的潜伏期和诱发电位的波幅。结果：复合有许旺细胞的小肠黏膜下层桥接神经组可见有再生神经组织长过缺损,呈条索状连续,且神经纤维多集中在小肠黏膜下层形成的桥接管周缘区域,而中心区域可见胶原组织且孔隙较多。复合有许旺细胞的小肠黏膜下层桥接神经组潜伏期的延迟率均高于自体神经移植组（P〈0.05）,而诱发电位的波幅恢复率均低于自体神经对照组（P〈0.05）。复合有许旺细胞的小肠黏膜下层桥接神经组轴突的平均直径、单位面积的轴突数量和神经组织所占的百分比均低于自体神经移植组（P〈0.05）。结论：复合有许旺细胞的小肠黏膜下层具有促进周围神经轴突再生的作用,但较自体神经移植略差。     

活性组织工程神经移植体桥接坐骨神经损伤：存活时间及功能恢复的量化评估

目的:利用组织工程方法制备的神经组织替代物桥接大鼠坐骨神经缺损,观察移植体的存活时间和神经功能指数。方法:实验于2001-04/2003-01在宾夕法尼亚大学神经外科颅脑创伤中心实验室完成。实验方法:利用神经轴索可以体外机械拉长的特性,将背根神经节神经元和拉长的轴索经凝胶处理后,一并卷入可吸收的聚乙醇酸导管内,制备出具有生物学活性的组织工程神经移植体。选用成年雄性SD大鼠40只,按随机数字表法分为4组,每组10只。建立大鼠坐骨神经损伤模型,组织工程替代物移植组将长约12mm的组织工程神经移植体桥接于坐骨神经缺损处;自体神经移植组将切除的坐骨神经近远端调转后重新缝合回缺损处;损伤模型组切除神经后无修复;对照组未造成损伤。实验评估:术后15周,分别对各组大鼠进行行为学评估,比较坐骨神经功能指数,其绝对数值与坐骨神经功能呈负相关。术后16周,处死动物前检测坐骨神经的传导速度,处死动物后行病理学检查,坐骨神经标本切片分别行苏木精-伊红、降钙素基因相关的缩氨酸抗体(背根神经节神经元标记物)、神经丝蛋白和髓鞘染色。结果:40只大鼠全部进入结果分析,无脱失。①术后15周,损伤模型组大鼠的坐骨神经功能指数绝对值高于组织工程替代物移植组和自体神经移植组(-94.3±2.55,-80.0±1.2,-82.7±2.7,P<0.05),两移植组差异无显著性意义(P>0.05)。对照组大鼠的坐骨神经功能指数为(-6.08±1.6),其绝对值显著低于其他3组(P<0.05)。②术后16周,对照组、组织工程替代物移植组、自体神经移植组大鼠的坐骨神经传导速度分别为(51.2±3.1,12.4±2.3,12.0±2.5)m/s,损伤模型组无动作电位引出,对照组大鼠的坐骨神经传导速度高于其他各组(P<0.01),两移植组差异无显著性意义(P>0.05)。③术后16周,自体神经移植组和替代物移植组中,大体检查可见相对正常的神经组织通过缺损区,聚乙醇酸导管基本已完全吸收。苏木精-伊红染色在替代物移植组大鼠的损伤区内发现大量的神经元细胞,降钙素基因相关的缩氨酸抗体和神经丝蛋白双重免疫组织荧光化学检查证实为背根神经节神经元。髓鞘染色可见缺损区内大量髓鞘包裹的轴突。结论:组织工程制备的神经组织替代物能够在移植受体内长期存活,并与受体神经结合促进神经功能恢复,在修复神经缺损、促进功能恢复方面与自体神经具有近似的能力。     

人胚雪旺细胞组织工程神经修复坐骨神经缺损的实验研究

目的：探索人胚雪旺细胞作为组织工程的种子细胞修复周围神经缺损的可行性。方法：通过组织工程方法用PLGA导管和polyglactin 910纤维负载人胚雪旺细胞预先构置好人工神经，然后用于修复大鼠20mm的坐骨神经缺损，并与神经切断后原位缝合以及用单纯的PLGA导管进行修复的实验组进行对照。通过活体肢体功能观察、靶器官肌肉测量、电生理检测、辣根过氧化物酶示踪、连续组织切片图像分析以及透射电镜等检查神经再生情况。结果：人工神经修复组神经再生良好，效果接近于神经原位缝合组，明显优于单纯的PLGA导管修复组。结论：人胚雪旺细胞构建的人工神经可以修复20mm的周围神经缺损。     

合成材料神经导管与自体神经移植修复周围神经缺损的比较

背景：生物可降解材料制成的神经导管可在体内降解,避免出现的神经卡压等问题,因而受到越来越多的关注. 目的：比较自体神经移植与3种合成可生物降解材料神经导管在修复周围神经损伤的效果差异. 方法：通过电生理学检测,形态学观察等神经恢复效果评价方法,对比分析近年来常用的胶原神经导管、DL-乳酸-ε-己内酯神经导管、聚乙醇酸神经导管与自体神经移植修复周围神经缺损的效果. 结果与结论：虽然神经导管与自体神经移植相比在理论上有其优势的一面,但不同合成材料的神经导管之间在神经功能恢复中存在明显差异性,DL-乳酸-ε-己内酯神经导管修复效果与自体神经移植无明显差异,是较为理想的神经导管材料,聚乙醇酸神经导管因自身的因素影响其降解性能,在3种神经导管中的修复周围神经损伤效果最差,胶原神经导管需要交联剂改善其机械性能,其修复周围神经损伤效果居于前两者之间,因此,这3种神经导管在神经功能再生方面还有潜在的缺陷,不能完全替代自体神经移植,而且3者之间的性价比,还缺少足够的大样本长期随机对照实验结果来验证,还需要进一步的实验观察.     

新型仿生人工神经导管诱导犬周围神经再生过程的组织学观察

背景:前期动物实验已经证明,精氨酸-甘氨酸-天冬氨酸多肽接枝聚(羟基乙酸-L-赖氨酸-乳酸)/β-磷酸三钙/神经生长因子导管可以修复大鼠坐骨神经10mm缺损,该材料具有良好的生物相容性和细胞亲和性。目的:观察精氨酸-甘氨酸-天冬氨酸多肽接枝聚(羟基乙酸-L-赖氨酸-乳酸)/聚乳酸/β-磷酸三钙/神经生长因子导管诱导犬周围神经再生过程的组织学变化。方法:取健康成年杂种犬12只,建立30mm腓总神经缺损模型,用精氨酸-甘氨酸-天冬氨酸多肽接枝聚(羟基乙酸-L-赖氨酸-乳酸)/聚乳酸/β-磷酸三钙/神经生长因子人工神经导管进行桥接修复。结果与结论:修复后3个月时在神经远端即可发现新生神经纤维,随着时间的推移,再生神经轴突直径及髓鞘厚度不断增加,9个月时再生神经中可见较多发育成熟的有髓神经纤维。胫骨前肌损伤后出现逐渐萎缩,修复后6,9个月萎缩肌肉逐渐恢复。从组织学角度证实了精氨酸-甘氨酸-天冬氨酸多肽接枝聚(羟基乙酸-L-赖氨酸-乳酸)/聚乳酸/β-磷酸三钙/神经生长因子导管可修复大动物粗大神经缺损。     

The effects of low-intensity ultrasound on peripheral nerve regeneration in poly(DL-lactic acid-co-glycolic acid) conduits seeded with Schwann cells

This study attempted to improve the efficacy of peripheral nerve regeneration, using the stimulus of low-intensity ultrasound (US) on poly(DL-lactic acid-co-glycolic acid) (PLGA) nerve guidance conduits seeded with Schwann cells. The possible differences between the ultrasonic effects of biodegradable and nonbiodegradable materials used as conduits were also investigated, by comparison with a group of silicone conduits. The PLGA conduits were seeded with or without Schwann cells (6 x 10(3) cells). All conduits were implanted 10 mm into right sciatic nerve defects in rats and underwent 12 ultrasonic treatment sessions over 2 weeks. Ultrasound was applied at a frequency of 1 MHz and an intensity of 0.2 W/cm2 spatial average temporal peak (SATP) for 5 min/day. Histologic analysis was used to evaluate the recovery of the nerve after 6 weeks. Ultrasonically stimulated animals, especially those whose PLGA conduits, seeded with Schwann cells, exhibited considerably more myelinated axons with a larger mean area at the midconduit of the implanted grafts than those in any other group. Ultrasonic stimulation of a silicone conduit induced the generation of mass fibrous tissues that covered the nerve conduits and retarded axon regeneration. These results showed that ultrasonic stimulation may directly stimulate the seeded Schwann cells within the PLGA conduits to regenerate nerves. Nevertheless, the applying of US may not allow incorporation with the silicone rubber as a material from which to form nerve guidance conduits.     

HRP神经逆行示踪评价GDNF修饰的神经移植复合体对大鼠脊髓运动神经元的保护作用

目的：采用大鼠坐骨神经缺损桥接动物模型,应用霍乱毒素B-辣根过氧化物酶（CB-HRP）神经逆行示踪技术对构建的GDNF修饰的神经移植复合体的运动神经元保护作用进行评价.方法：20只成年Wistar大鼠随机分为4组：A组（n=5）细胞外基质凝胶-PLGA管桥接组;B组（n=5）雪旺细胞-细胞外基质凝胶-PLGA管桥接组;C组（n=5）GDNF基因修饰的雪旺细胞-细胞外基质凝胶-PLGA管桥接组;D组（n=5）自体神经桥接组.损伤各组12周时应用辣根过氧化物酶神经逆行示踪技术进行脊髓前角运动神经元的再生评价.结果：12周时脊髓前角运动神经元再生评价结果提示：C组优于A、B组,而与D组相比差异无显著性意义.结论：雪旺细胞的转基因处理可能弥补单纯细胞移植神经营养因子含量的不足,而可能达到与自体神经移植相似的效果.     

The advances in nerve tissue engineering: From fabrication of nerve conduit to in vivo nerve regeneration assays

Peripheral nerve damage is a common clinical complication of traumatic injury occurring after accident, tumorous outgrowth, or surgical side effects. Although the new methods and biomaterials have been improved recently, regeneration of peripheral nerve gaps is still a challenge. These injuries affect the quality of life of the patients negatively. In the recent years, many efforts have been made to develop innovative nerve tissue engineering approaches aiming to improve peripheral nerve treatment following nerve injuries. Herein, we will not only outline what we know about the peripheral nerve regeneration but also offer our insight regarding the types of nerve conduits, their fabrication process, and factors associated with conduits as well as types of animal and nerve models for evaluating conduit function. Finally, nerve regeneration in a rat sciatic nerve injury model by nerve conduits has been considered, and the main aspects that may affect the preclinical outcome have been discussed.     

Neurotrophin releasing single and multiple lumen nerve conduits.

Tissue engineering strategies for nerve repair employ polymer conduits termed guidance channels and bridges to promote regeneration for peripheral nerve injury and spinal cord injury, respectively. An approach for fabrication of nerve conduits with single and multiple lumens capable of controlled release of neurotrophic factors was developed. These conduits were fabricated from a mixture of poly(lactide-co-glycolide) (PLG) microspheres and porogen (NaCl) that was loaded into a mold and processed by gas foaming. The porosity and mechanical properties of the constructs were regulated by the ratio of porogen to polymer microsphere. The neurotrophin, nerve growth factor (NGF), was incorporated into the conduit by either mixing the protein with microspheres or encapsulating the protein within microspheres prior to gas foaming. A sustained release was observed for at least 42 days, with the release rate controlled by method of incorporation and polymer molecular weight. Released NGF retained its bioactivity, as demonstrated by its ability to stimulate neurite outgrowth from primary dorsal root ganglion (DRG). In vivo results indicate that conduits retain their original architecture, and allow for cellular infiltration into the channels. Polymer conduits with controllable lumen diameters and protein release may enhance nerve regeneration by guiding and stimulating neurite outgrowth.     

Nanofibrous nerve conduit‐enhanced peripheral nerve regeneration

Fibre structures represent a potential class of materials for the formation of synthetic nerve conduits due to their biomimicking architecture. Although the advantages of fibres in enhancing nerve regeneration have been demonstrated, in vivo evaluation of fibre size effect on nerve regeneration remains limited. In this study, we analyzed the effects of fibre diameter of electrospun conduits on peripheral nerve regeneration across a 15‐mm critical defect gap in a rat sciatic nerve injury model. By using an electrospinning technique, fibrous conduits comprised of aligned electrospun poly (ε‐caprolactone) (PCL) microfibers (981 ± 83 nm, Microfiber) or nanofibers (251 ± 32 nm, Nanofiber) were obtained. At three months post implantation, axons regenerated across the defect gap in all animals that received fibrous conduits. In contrast, complete nerve regeneration was not observed in the control group that received empty, non‐porous PCL film conduits (Film). Nanofiber conduits resulted in significantly higher total number of myelinated axons and thicker myelin sheaths compared to Microfiber and Film conduits. Retrograde labeling revealed a significant increase in number of regenerated dorsal root ganglion sensory neurons in the presence of Nanofiber conduits (1.93 ± 0.71 × 10³ vs. 0.98 ± 0.30 × 10³ in Microfiber, p < 0.01). In addition, the compound muscle action potential (CMAP) amplitudes were higher and distal motor latency values were lower in the Nanofiber conduit group compared to the Microfiber group. This study demonstrated the impact of fibre size on peripheral nerve regeneration. These results could provide useful insights for future nerve guide designs. Copyright © 2012 John Wiley & Sons, Ltd.     

Hydrogel composition and laser micropatterning to regulate sciatic nerve regeneration

Treatment of peripheral nerve injuries has evolved over the past several decades to include the use of sophisticated new materials endowed with trophic and topographical cues that are essential for in vivo nerve fibre regeneration. In this research, we explored the use of an advanced design strategy for peripheral nerve repair, using biological and semi‐synthetic hydrogels that enable controlled environmental stimuli to regenerate neurons and glial cells in a rat sciatic nerve resection model. The provisional nerve growth conduits were composed of either natural fibrin or adducts of synthetic polyethylene glycol and fibrinogen or gelatin. A photo‐patterning technique was further applied to these 3D hydrogel biomaterials, in the form of laser‐ablated microchannels, to provide contact guidance for unidirectional growth following sciatic nerve injury. We tested the regeneration capacity of subcritical nerve gap injuries in rats treated with photo‐patterned materials and compared these with injuries treated with unpatterned hydrogels, either stiff or compliant. Among the factors tested were shear modulus, biological composition, and micropatterning of the materials. The microchannel guidance patterns, combined with appropriately matched degradation and stiffness properties of the material, proved most essential for the uniform tissue propagation during the nerve regeneration process.     

Functional collagen conduits combined with human mesenchymal stem cells promote regeneration after sciatic nerve transection in dogs

Numerous studies have focused on the development of novel and innovative approaches for the treatment of peripheral nerve injury using artificial nerve guide conduits. In this study, we attempted to bridge 3.5‐cm defects of the sciatic nerve with a longitudinally oriented collagen conduit (LOCC) loaded with human umbilical cord mesenchymal stem cells (hUC‐MSCs). The LOCC contains a bundle of longitudinally aligned collagenous fibres enclosed in a hollow collagen tube. Our previous studies showed that an LOCC combined with neurotrophic factors enhances peripheral nerve regeneration. However, it remained unknown whether an LOCC seeded with hUC‐MSCs could also promote regeneration. In this study, using various histological and electrophysiological analyses, we found that an LOCC provides mechanical support to newly growing nerves and functions as a structural scaffold for cells, thereby stimulating sciatic nerve regeneration. The LOCC and hUC‐MSCs synergistically promoted regeneration and improved the functional recovery in a dog model of sciatic nerve injury. Therefore, the combined use of an LOCC and hUC‐MSCs might have therapeutic potential for the treatment of peripheral nerve injury.