神经组织工程支架或异种神经移植在面神经缺损中的应用

背景：了解面神经损伤的修复方法,以及各种组织支架的特性与优势,对于修复方法与材料的合理选择是十分必要的。 目的：总结神经组织工程支架或异种神经移植在面神经缺损中的应用进展。 方法：应用计算机检索PubMed数据库及CNKI数据库,在标题和摘要中以“组织工程支架,神经移植,面神经,修复”或“tissue engineering scaffolds,nerve transplantation,facial,repair”为检索词进行检索。根据纳入标准选择21篇文献进行综述。 结果与结论：面神经缺损后立即直接缝合神经的断端是最好的修复方法。自体神经移植受神经移植体来源之限,常造成供区失神经支配;以及产生束外有髓和无髓轴突无规则生长会导致神经纤维错向再生,造成严重的联带运动的不足。异体或异种神经移植法虽然取得了一定的效果,但仍处于动物实验的研究阶段,尚难以应用于临床。     

4000/三种不同组织移植方法一期修复外伤性甲床缺损的比较

目的：探讨一期修复甲床缺损的不同治疗方法,综合评价其功能恢复情况。 方法：①对象：选择2002-12/ 2009-02在解放军第458医院整形外科就诊的40例51指（拇指11指,示指22指,中指14指,环指4指）甲床缺损就诊者。②方法：a：在骨膜存在条件下,当甲床缺损≥5 mm,但小于同指甲床面积的1/3者,采用同指中厚断层残留甲床移植;b：当甲床缺损在大于同指甲床面积的1/3者或合并两指甲床缺损时,采用第一、二足趾为供区;c：当末节指骨骨膜缺损时,甲床缺损面积在1/3-1/2范围内,采用有血供的断层甲床组织瓣局部转移。③评估：伤者术后随访,观察指甲形态和手指功能。 结果：经过1月-2年随访,平均6月。86.3%的病例获得良好的外形及对捏、持物功能。 结论：根据不同伤情,采用对应甲床修复方法。可达到一期修复甲床缺损的目的,恢复指甲形态和手指功能。     

神经移植在面神经功能重建中的应用

面神经损伤引起的面部功能障碍可由多种原因造成,其不仅导致患者生活质量下降,而且进一步影响正常社交活动,因此面神经修复的主要目的在于提高患者面部对称性以及恢复社交能力,目前治疗方式包括药物治疗、康复治疗以及各类外科干预等。轻症初期面瘫患者往往会先选择保守治疗,对于保守无效或中重度面瘫的情况,神经移植是有效且可靠的治疗手段,主要术式包括咬肌神经-面神经移植(MFNN)、舌下神经-面神经移植(HFA)、跨面神经移植及其改良、联合的术式,迄今仍无统一的治疗指南。本文就面神经功能重建中不同神经移植术式进行简单地描述,重点对比其优缺点、适应证以及术后疗效,为日后临床术式选择提供一些参考。     

保护神经系膜式耳大神经移植术在面神经缺损修复中的应用

目的 对临床上面神经缺损的耳大神经移植修复术的术式进行研究.方法 对因腮腺区恶性肿瘤切除面神经后即刻行耳大神经移植的患者,静态和动态观察本术式神经修复后表情肌功能恢复的效果并监测神经传导速度的变化,并与单纯耳大神经游离移植术式进行比较.结果 行保护神经系膜式带蒂耳大神经移植术的78例患者中,有72例面神经功能完全恢复,恢复率为92.3%;面神经功能恢复时间为18～25周,平均21.5周.行单纯耳大神经游离移植的46例患者中,有25例面神经功能完全恢复,恢复率为54.3%;面神经功能恢复时间32～41周,平均36.4周.结论 保护神经系膜式耳大神经移植术修复面神经缺损较单纯用耳大神经游离移植修复有明显的统计学意义(χ2=24.8,P＜0.01),是目前修复面神经一种较理想的方法.     

4000/人发角蛋白非神经移植材料的基础研究（英文自译）

①目的　研究人发角蛋白非神经移植材料的解剖学特点和组织相容性,及其对周围神经缺损的修复效果。②方法　Wistar 大白鼠18 只随机分成3 组,将其坐骨神经切取10 mm ,分别用人发角蛋白非神经移植材料(实验组) 、大白鼠自体骨骼肌(对照Ⅰ组) 和未经特殊处理的人发(对照Ⅱ组) 连接神经两断端。术后不同时间进行 组织形态及解剖学观察。③结果　术后第8 周实验组坐骨神经两断端之间出现白色新生组织;第12 周白色新生组织出现于移植材料腔隙;第24 周移植材料腔隙被充满,人发被初步降解,光镜下可见人发周围有大量呈无序排列的再生神经纤维,透射电镜下可见人发周围雪旺细胞增殖并形成髓鞘。对照组未出现上述变化。④结论　人发角蛋白非神经移植材料的组织相容性好,并可诱导神经纤维再生,是用于修复神经缺损较为理想的材料。     

外源性神经生长因子诱导下自体静脉桥接修复神经缺损

背景：采用自体神经游离移植修复神经缺损效果比较理想,但有其弊端。为此寻求一种更佳修复神经缺损的治疗方法。 目的：验证及外源性神经生长因子诱导下自体静脉桥接神经缺损对神经再生的影响。 方法：采用Wistar大鼠建立周围神经缺损模型。随机将大鼠分为3组。实验组采用自体静脉桥接并注入神经生长因子;对照组采用自体静脉桥接并注入生理盐水;标准组采用自体神经桥接。分别于术后1,3个月,对实验动物进行活体观察,电生理检测及组织学检测。 结果与结论：3组实验动物均有神经再生及修复表现,但程度不同。实验组失神经表现恢复的较对照组早,电生理检测运动神经传导速度快,组织学检查再生神经纤维数量及质量明显高于对照组(P < 0.05);与“金标准”的自体神经桥接组比较无显著性意义(P > 0.05)。结果提示采用自体静脉桥接+神经生长因子诱导对周围神经缺损后的再生、修复具有有促进作用,可以使再生神经纤维的数量增加并显著提高再生神经纤维质量。     

面神经损伤的修复机制研究

面神经是极易受损的颅神经,外伤、手术操作、炎症或肿瘤等均可造成它的损伤。至今对于修复和重建受损神经的技术并未达到令人满意的地步,其中一个主要原因是神经修复及再生生物学机制尚未完全清楚。最新文献表明,神经损伤后的修复不仅与神经细胞自身密切相关,而且周围非神经细胞也参与了神经组织的再生。本文旨在综述近年来这方面的实验研究进展。     

脉络丛移植对中枢神经损伤的修复作用

轴突都有再生的能力,但是中枢神经受损后未见明显的轴突再生,这是由于轴突固有的再生能力较差以及轴突生长的微环境阻滞所致.近年来,随着对脉络丛的结构和功能的研究增多,学者们认为脉络丛有助于轴突的再生和中枢神经损伤的修复.     

化学去细胞同种异体神经移植修复大鼠骶1神经缺损

背景：自体神经移植是修复周围神经损伤中最常用的方法。目的：探讨化学去细胞神经修复大鼠骶1神经缺损的效果,以期寻找修复周围神经缺损较为理想的方法和材料。方法：取SD大鼠骶1神经,采用化学去细胞法处理大鼠骶1神经的免疫原性成分,使其成为去细胞神经。将Wistar大鼠右侧骶1神经制成1 cm缺损模型,用SD大鼠去细胞同种异体神经移植修复大鼠骶1神经的缺损。结果与结论：与术前相比,术后8周逼尿肌漏尿点降低,膀胱最大容积和膀胱顺应性升高(P < 0.05)。神经纤维细丝蛋白染色结果显示,右侧经同种异体神经移植修复的神经吻合口断端被染成绿色,神经纤维排列整齐分布均一,再生神经轴突长入远端神经。左侧正常神经形态均一,神经纤维排列整齐分布均一未见轴突长入远端神经。结果表明,化学去细胞同种异体神经的抗原性明显降低,可修复高等哺乳类动物的周围神经损伤。     

Autogenous inside-out versus standard vein and skeletal muscle-combined grafting for facial nerve repair

BACKGROUND: In the repair of nerve defects, collapse of the venous wall, as a result of vein grafting alone, could impede nerve regeneration. Therefore, vein lumens filled with muscle and nerve segments have been used to bridge nerve defects. OBJECTIVE: To compare the effects of autogenous, inside-out, vein-skeletal, muscle-combined grafting versus standard, vein-skeletal, muscle-combined grafting for the repair of facial nerve defects. DESIGN, TIME AND SETTING: A randomized, controlled, neuroanatomical, animal study was erformed at the Animal Experimental Center and Laboratories of the Capital Medical University Xuanwu Hospital and the Peking Union Medical College Hospital from September 2007 to October 2008. MATERIALS: A total of 10 healthy, male, New Zealand rabbits, aged 6 months, were randomly assigned to inside-out, vein-skeletal, muscle-combined grafting and standard, vein-skeletal, muscle-combined grafting groups, with 5 rabbits in each group. METHODS: A 20-mm gap in the buccal branch of the right facial nerve was made in each animal, which was respectively repaired with inside-out, vein-skeletal, muscle-combined grafts or standard vein-skeletal muscle-combined grafts. MAIN OUTCOME MEASURES: At 6 months after implantation, evoked maximal compound muscle action potentials were recorded on bilateral facial nerves using electromyogram. Myelinated nerve fibers of the regenerating nerves were quantified using myelin sheath osmic acid staining. RESULTS: There was no significant difference between the groups in terms of ratios of bilateral amplitude and latency of compound muscle action potential (P> 0.05). Moreover, morphology of regenerating nerves and quantity of myelinated nerve fibers were similar between the groups (P > 0.05). CONCLUTION: Compared with standard vein grafting, the inside-out vein grafting did not significantly improve nerve regeneration. Therefore, it is not necessary to utilize inside-out vein grafting for the repair of nerve defects, in particular with the combined use of autogenous vein and skeletal muscle grafts.     

Skeletal muscle-derived cells repair peripheral nerve defects in mice

Skeletal muscle-derived cells have strong secretory function,while skeletal muscle-derived stem cells,which are included in muscle-derived cells,can differentiate into Schwann cell-like cells and other cell types.However,the effect of muscle-derived cells on peripheral nerve defects has not been reported.In this study,5-mm-long nerve defects were created in the right sciatic nerves of mice to construct a peripheral nerve defect model.Adult female C57BL/6 mice were randomly divided into four groups.For the muscle-derived cell group,muscle-derived cells were injected into the catheter after the cut nerve ends were bridged with a polyurethane catheter.For external oblique muscle-fabricated nerve conduit and polyurethane groups,an external oblique muscle-fabricated nerve conduit or polyurethane catheter was used to bridge the cut nerve ends,respectively.For the sham group,the sciatic nerves on the right side were separated but not excised.At 8 and 12 weeks post-surgery,distributions of axons and myelin sheaths were observed,and the nerve diameter was calculated using immunofluorescence staining.The number,diameter,and thickness of myelinated nerve fibers were detected by toluidine blue staining and transmission electron microscopy.Muscle fiber area ratios were calculated by Masson’s trichrome staining of gastrocnemius muscle sections.Sciatic functional index was recorded using walking footprint analysis at 4,8,and 12 weeks after operation.The results showed that,at 8 and 12 weeks after surgery,myelin sheaths and axons of regenerating nerves were evenly distributed in the muscle-derived cell group.The number,diameter,and myelin sheath thickness of myelinated nerve fibers,as well as gastrocnemius muscle wet weight and muscle area ratio,were significantly higher in the muscle-derived cell group compared with the polyurethane group.At 4,8,and 12 weeks post-surgery,sciatic functional index was notably increased in the muscle-derived cell group compared with the polyurethane group.These criteria of the muscle-derived cell group were not significantly different from the external oblique muscle-fabricated nerve conduit group.Collectively,these data suggest that muscle-derived cells effectively accelerated peripheral nerve regeneration.This study was approved by the Animal Ethics Committee of Plastic Surgery Hospital,Chinese Academy of Medical Sciences(approval No.040)on September 28,2016.     

Effect of Intertrial Delay on Whole Nerve Cuff Recordings of Muscle Afferents in Rabbits

Objective. The effect of the stationary period on the muscle afferent responsiveness to passive stretch was studied to determine if muscle afferent activity might be suitable as feedback in motor‐neural prostheses control. Methods. Muscle afferent activity was recorded using nerve cuff electrodes applied individually to the tibial and peroneal components of the sciatic nerve in five rabbit preparations. The ankle joint was rotated using a servomotor. The delay between trapezoidal movements was varied (excursion = 30°, velocity = 20°/s) and the duration was increased stepwise in successive trials(2 s, 5 s, 10 s, 20 s, 30 s, and 180 s). Results. An increase in amplitude of the afferent activity with increasing intertrial delay was observed. The afferent responses following a 2‐s delay were subtracted from the responses following each of the remaining intervals (5 s‐2 s, 10 s‐2 s, 20 s‐2 s, 30 s‐2 s and 180 s‐2 s) and were then compared. During the ramp phase a statistically significant difference was found in 85% and 76% of the cases for the tibial and peroneal nerve responses. Significant differences were below 21% for both nerves during four other phases examined. Conclusions. It is suggested that the enhancement in afferent responses caused by the increased intertrial delay may be explained by the change in the mechanical properties of the intrafusal and extrafusal muscle fibers. The consequences of this, when applying muscle afferent activity in motor‐neuro prostheses, are discussed.     

A collagen-based nerve guide conduit for peripheral nerve repair: an electrophysiological study of nerve regeneration in rodents and nonhuman primates

When a peripheral nerve is severed and left untreated, the most likely result is the formation of an endbulb neuroma; this tangled mass of disorganized nerve fibers blocks functional recovery following nerve injury. Although there are several different approaches for promoting nerve repair, which have been greatly refined over recent years, the clinical results of peripheral nerve repair remain very disappointing. In this paper we compare the results of a collagen nerve guide conduit to the more standard clinical procedure of nerve autografting to promote repair of transected peripheral nerves in rats and nonhuman primates. In rats, we tested recovery from sciatic nerve transection and repair by 1) direct microsurgical suture, 2) 4 mm autograft, or 3) entubulation repair with collagen-based nerve guide conduits. Evoked muscle action potentials (MAP) were recorded from the gastrocnemius muscle at 4 and 12 weeks following sciatic nerve transection. At 4 weeks the repair group of direct suture demonstrated a significantly greater MAP, compared to the other surgical repair groups. However, at 12 weeks all four surgical repair groups displayed similar levels of recovery of the motor response. In six adult male Macaca fascicularis monkeys the median nerve was transected 2 cm above the wrist and repaired by either a 4 mm nerve autograft or a collagen-based nerve guide conduit leaving a 4 mm gap between nerve ends. Serial studies of motor and sensory fibers were performed by recording the evoked MAP from the abductor pollicis brevis muscle (APB) and the sensory action potential (SAP) evoked by stimulation of digital nerves (digit II), respectively, up to 760 days following surgery. Evoked muscle responses returned to normal baseline levels in all cases. Statistical analysis of the motor responses, as judged by the slope of the recovery curves, indicated a significantly more rapid rate of recovery for the nerve guide repair group. The final level of recovery of the MAP amplitudes was not significantly different between the groups. In contrast, the SAP amplitude only recovered to the low normal range and there were no statistically significant differences between the two groups in terms of sensory recovery rates. The rodent and primate studies suggest that in terms of recovery of physiological responses from target muscle and sensory nerves, entubulation repair of peripheral nerves with a collagen-based nerve guide conduit over a short nerve gap (4 mm) is as effective as a standard nerve autograft.(ABSTRACT TRUNCATED AT 400 WORDS)     

Agmatine treatment and vein graft reconstruction enhance recovery after experimental facial nerve injury

The rate of nerve regeneration is a critical determinant of the degree of functional recovery after injury. Here, we sought to determine whether treatment with the neuroprotective compound, agmatine, with or without nerve reconstruction utilizing a regional autogenous vein graft would accelerate the rate of facial nerve regeneration. Experiments compared the following seven groups of adult male rats: (A) Intact untreated controls. (B) Sham operation with interruption of the nerve blood supply (controls). (C) Transection of the mandibular branch of the facial nerve (generating a gap of 3 mm) followed by saline treatment. (D) Nerve transection with unsutured autogenous vein (external jugular) graft reconstruction plus saline treatment. (E) Nerve transection with sutured vein graft approximation (coaptation of the proximal and distal nerve stumps) plus saline. (F) Nerve transection with sutured vein graft followed by agmatine treatment (four daily intraperitoneal injections of 100 mg/kg agmatine sulfate). (G) Nerve transection with unsutured vein graft followed by agmatine treatment. Functional recovery, as assessed by grading vibrissae movements and by recording nerve conduction velocity and numbers of regenerated axons, indicated that either vein reconstruction or agmatine treatment resulted in accelerated and more complete recovery as compared with controls. But best results were observed in animals that underwent combined treatment, i.e., vein reconstruction plus agmatine injection. We conclude that agmatine treatment can accelerate facial nerve regeneration and that agmatine treatment together with autogenous vein graft offers an advantageous alternative to other facial nerve reconstruction procedures.     

Modification of tubular chitosan-based peripheral nerve implants: applications for simple or more complex approaches

Surgical treatment of peripheral nerve injuries is still a major challenge in human clinic.Up to now,none of the well-developed microsurgical treatment options is able to guarantee a complete restoration of nerve function.This restriction is also effective for novel clinically approved artificial nerve guides.In this review,we compare surgical repair techniques primarily for digital nerve injuries reported with relatively high prevalence to be valuable attempts in clinical digital nerve repair and point out their advantages and shortcomings.We furthermore discuss the use of artificial nerve grafts with a focus on chitosan-based nerve guides,for which our own studies contributed to their approval for clinical use.In the second part of this review,very recent future perspectives for the enhancement of tubular(commonly hollow)nerve guides are discussed in terms of their clinical translatability and ability to form three-dimensional constructs that biomimick the natural nerve structure.This includes materials that have already shown their beneficial potential in in vivo studies like fibrous intraluminal guidance structures,hydrogels,growth factors,and approaches of cell transplantation.Additionally,we highlight upcoming future perspectives comprising co-application of stem cell secretome.From our overview,we conclude that already simple attempts are highly effective to increase the regeneration supporting properties of nerve guides in experimental studies.But for bringing nerve repair with bioartificial nerve grafts to the next level,e.g.repair of defects>3 cm in human patients,more complex intraluminal guidance structures such as innovatively manufactured hydrogels and likely supplementation of stem cells or their secretome for therapeutic purposes may represent promising future perspectives.     

Changes in a rat facial muscle after facial nerve injury and repair

This study describes changes in a rat facial muscle innervated by the mandibular and buccal facial nerve branches 4 months after nerve injury and repair. The following groups were studied: (A) normal controls; (B) spontaneous reinnervation by collateral or terminal sprouting; (C) reinnervation after surgical repair of the mandibular branch; and (D) chronic denervation. The normal muscle contained 1200 exclusively fast fibers, mainly myosin heavy chain (MyHC) IIB fibers. In group B, fiber number and fiber type proportions were normal. In group C, fiber number was subnormal. Diameters and proportions of MyHC IIA and hybrid fibers were above normal. The proportion of MyHC IIB fibers was subnormal. Immediate and delayed repair gave similar results with respect to the parameters examined. Group D rats underwent severe atrophic and degenerative changes. Hybrid fibers prevailed. These data suggest that spontaneous regeneration of the rat facial nerve is superior to regeneration after surgical repair and that immediacy does not give better results than moderate delay with respect to surgical repair. Long delays are shown to be detrimental.     

Genetic and clinical characteristics of skeletal and cardiac muscle in patients with lamin A/C gene mutations

Alterations of the lamin A/C (LMNA) gene are associated with different clinical entities, including disorders that affect skeletal and cardiac muscle, peripheral nerves, metabolism, bones, and disorders that cause premature aging. In this article we review the clinical and genetic characteristics of cardiac and skeletal muscle diseases related to alterations in the LMNA gene. There is no single explanation of how LMNA gene alterations may cause these disorders; however, important goals have been achieved in understanding the pathogenic effects of LMNA gene mutations on cardiac and skeletal muscle. Muscle Nerve, 48: 161–170, 2013