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1An update–tissue engineered nerve grafts for the repair of peripheral nerve injuries显示文摘Peripheral nerve injuries(PNI) are caused by a range of etiologies and result in a broad spectrum of disability. While nerve autografts are the current gold standard for the reconstruction of extensive nerve damage, the limited supply of autologous nerve and complications associated with harvesting nerve from a second surgical site has driven groups from multiple disciplines, including biomedical engineering, neurosurgery, plastic surgery, and orthopedic surgery, to develop a suitable or superior alternative to autografting. Over the last couple of decades, various types of scaffolds, such as acellular nerve grafts(ANGs), nerve guidance conduits, and non-nervous tissues, have been filled with Schwann cells, stem cells, and/or neurotrophic factors to develop tissue engineered nerve grafts(TENGs). Although these have shown promising effects on peripheral nerve regeneration in experimental models, the autograft has remained the gold standard for large nerve gaps. This review provides a discussion of recent advances in the development of TENGs and their efficacy in experimental models. Specifically, TENGs have been enhanced via incorporation of genetically engineered cells, methods to improve stem cell survival and differentiation, optimized delivery of neurotrophic factors via drug delivery systems(DDS), co-administration of platelet-rich plasma(PRP), and pretreatment with chondroitinase ABC(Ch-ABC). Other notable advancements include conduits that have been bioengineered to mimic native nerve structure via cell-derived extracellular matrix(ECM) deposition, and the development of transplantable living nervous tissue constructs from rat and human dorsal root ganglia(DRG) neurons. Grafts composed of non-nervous tissues, such as vein, artery, and muscle, will be briefly discussed.Nitesh P.Patel Kristopher A.Lyon Jason H.Huang 2018Neural Regeneration Research2018,13,5:12
2Acellular allogeneic nerve grafting combined with bone marrow mesenchymal stem cell transplantation for the repair of long-segment sciatic nerve defects:biomechanics and validation of mathematical models显示文摘We hypothesized that a chemically extracted acellular allogeneic nerve graft used in combination with bone marrow mesenchymal stem cell transplantation would be an effective treatment for long-segment sciatic nerve defects.To test this,we established rabbit models of 30 mm sciatic nerve defects,and treated them using either an autograft or a chemically decellularized allogeneic nerve graft with or without simultaneous transplantation of bone marrow mesenchymal stem cells.We compared the tensile properties,electrophysiological function and morphology of the damaged nerve in each group.Sciatic nerves repaired by the allogeneic nerve graft combined with stem cell transplantation showed better recovery than those repaired by the acellular allogeneic nerve graft alone,and produced similar results to those observed with the autograft.These findings confirm that a chemically extracted acellular allogeneic nerve graft combined with transplantation of bone marrow mesenchymal stem cells is an effective method of repairing long-segment sciatic nerve defects.Ya-jun Li Bao-lin Zhao Hao-ze Lv Zhi-gang Qin Min Luo 2016Neural Regeneration Research2016,11,8:8
3Repair of peripheral nerve defects with chemically extracted acellular nerve allografts loaded with neurotrophic factors-transfected bone marrow mesenchymal stem cells显示文摘Chemically extracted acellular nerve allografts loaded with brain-derived neurotrophic factor-transfected or ciliary neurotrophic factor-transfected bone marrow mesenchymal stem cells have been shown to repair sciatic nerve injury better than chemically extracted acellular nerve allografts alone, or chemically extracted acellular nerve allografts loaded with bone marrow mesenchymal stem cells. We hypothesized that these allografts compounded with both brain-derived neurotrophic factor- and ciliary neurotrophic factor-transfected bone marrow mesenchymal stem cells may demonstrate even better effects in the repair of peripheral nerve injury. We cultured bone marrow mesenchymal stem cells expressing brain-derived neurotrophic factor and/or ciliary neurotrophic factor and used them to treat sciatic nerve injury in rats. We observed an increase in sciatic functional index, triceps wet weight recovery rate, myelin thickness, number of myelinated nerve fibers, amplitude of motor-evoked potentials and nerve conduction velocity, and a shortened latency of motor-evoked potentials when allografts loaded with both neurotrophic factors were used, compared with allografts loaded with just one factor. Thus, the combination of both brain-derived neurotrophic factor and ciliary neurotrophic factor-transfected bone marrow mesenchymal stem cells can greatly improve nerve injury.Yan-ru Zhang Ka Ka Ge-chen Zhang Hui Zhang Yan Shang Guo-qiang Zhao Wen-hua Huang 2015Neural Regeneration Research2015,10,9:6
4透明质酸在去细胞异体神经移植中对瘢痕的影响显示文摘背景:在组织相容性、免疫排斥反应及修复后瘢痕影响程度等方面,去细胞异体神经移植修复周围神经缺损更接近自体神经。目前,已经有透明质酸应用于自体周围神经修复的研究,尚无透明质酸应用于异体神经移植修复周围神经损伤的报道。目的:探讨透明质酸在去细胞同种异体神经移植修复大鼠坐骨神经缺损中对吻合口瘢痕形成的影响。方法:36只SD大鼠随机分为3组,每组12只。3组大鼠均选取左后肢手术,手术将坐骨神经锐性切断后造成10 mm神经缺损。实验组异体神经移植后在两端吻合口应用透明质酸,对照组行单纯异体神经移植手术,自体神经移植组将自体神经切断后远近端倒置吻合。术后观察近端吻合口的愈合情况,评估近端吻合口的瘢痕成分。结果与结论:(1)大体观察:大鼠皮肤,肌肉筋膜愈合组间无差别,周围组织粘连情况比较,实验组优于对照组(P<0.05);(2)Masson染色:各组神经外膜均可见胶原沉积,实验组神经外膜胶原纤维排列整齐有序,胶原纤维量略少;对照组大量胶原纤维成堆积状,排列紊乱;自体神经移植组神经外膜胶原纤维较多,胶原纤维排列较整齐,但胶原纤维较稀疏;(3)Ⅰ,Ⅲ型胶原免疫组化灰度值:Ⅰ型胶原灰度值实验组高于对照组(P<0.05),Ⅲ型胶原灰度值实验组低于对照组(P<0.05),Ⅰ型+Ⅲ型胶原灰度值实验组、对照组及自体神经移植组比较差异无显著性意义(P>0.05);(4)结果提示,透明质酸在周围神经损伤修复过程中对Ⅰ,Ⅲ型胶原沉积具有调控作用,可增加Ⅲ型胶原沉积,减少Ⅰ型胶原沉积,从而减少瘢痕形成。刘英伟 张万里 池成涛 徐青雨 芦德智 2016中国组织工程研究2016,20,42:5
5冻融联合优化化学法制备粗大去细胞同种异体神经显示文摘背景:异体神经移植修复神经缺损需要面对和解决的是宿主免疫排斥反应问题。因此,如何避免、减轻免疫排斥反应是同种异体神经移植获得成功的关键因素。目的:探索新的异体神经预处理方法,清除犬周围神经中的许旺细胞和髓鞘,保留完整的基底膜,建立粗大异体神经移植物的预处理方法,获得去细胞异体神经移植物。方法:取健康成年杂种犬游离双侧坐骨神经,以冻融联合优化化学法对神经进行预处理,光、电镜观察其结构特征,组织学染色及Western blot分析其成分。结果与结论:预处理后的去细胞神经的延展性和神经外膜的弹韧性良好,许旺细胞和髓鞘被彻底清除,基底膜保留完整,去细胞神经为一没有细胞、髓鞘及其碎片的空的神经基膜管。结果表明该方法有效的清除了周围神经中主要抗原成分许旺细胞及髓鞘,并且保留了促神经再生的重要成分基底膜,可作为制备组织工程化神经较理想的方法。管树军 王伟 李岩 2015中国组织工程研究2015,19,12:2
6异种源性脱细胞神经支架修复坐骨神经损伤后再生的可行性显示文摘目的:评价异种脱细胞神经支架修复大鼠坐骨神经损伤的疗效。方法:以兔源性胫神经为原材料,通过萃取技术制备脱细胞神经支架;HE染色、甲苯胺蓝染色、免疫组化(IHC)、扫描电镜(SEM)、透射电镜(TEM)检测技术评价脱细胞效果;体内实验部分采用坐骨神经离断模型,按照移植物的不同,将SD大鼠随机分为两组:异种神经支架移植组(实验组)、自体神经移植组(对照组),术后12周内,流式细胞术检测大鼠外周血中CD3^+、CD4^+、CD8^+淋巴细胞含量,以判定机体免疫系统情况;通过神经功能测定及形态学手段评价10 mm缺损神经的修复效果。结果:支架内的细胞和髓鞘成分能够彻底去除,基底膜管状结构保留较为完整。术后1、4、12周时间点,实验组大鼠外周血CD3^+、CD4^+、CD8^+淋巴细胞含量与对照组比较,差异均无统计学意义(P>0.05)。4周及12周后,两组坐骨神经功能指数(SFI)比较差异均无统计学意义(P>0.05);实验组移植物内的再生轴突数量、再生髓鞘厚度方面与对照组比较,差异均无统计学意义(P>0.05)。结论:异种神经脱细胞支架干预10 mm大鼠坐骨神经缺损,并不会引起机体系统性排斥反应,同时能够有效促进损伤神经再生。陈少红 季婉青 侯博 2016中国医学创新2016,13,20:2
7含BMSCs的ANX移植联合G-CSF修复大鼠坐骨神经缺损的实验研究显示文摘目的:探讨复合骨髓基质细胞(BMSCs)的脱细胞异种神经移植体(ANX)移植及联合应用粒细胞集落刺激因子(G-CSF)修复大鼠坐骨神经缺损的效果。方法:将大鼠BMSCs种植到ANX内复合培养,制备大鼠坐骨神经10 mm缺损模型,SD大鼠随机分为4组(n=10):ANX移植组、ANX移植联合应用G-CSF组、复合BMSCs的ANX移植组和复合BMSCs的ANX移植联合应用G-CSF组。术后8周,行坐骨神经功能指数(SFI)和电生理检测;应用免疫荧光染色和实时荧光定量PCR检测再生神经内神经丝和神经营养因子的表达。结果:含BMSCs的ANX移植联合应用G-CSF组SFI、神经传导速度、再生纤维相对密度增高(P<0.05),神经营养因子表达增加(P<0.05)。结论:含BMSCs的ANX移植联合应用G-CSF可显著促进周围神经再生。贾桦 李伟丽 王涛 董毅 李军平 焦旭文 张莲香 王效军 何仲义 2016神经解剖学杂志2016,32,2:1
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