peripheral nerve repair

周围神经修复
  • 文章类型: Case Reports
    肱骨远端骨折的切开复位和内固定过程中尺神经的损伤是众所周知的现象。然而,植入物移除过程中尺神经损伤尚未得到很好的记录。我们在合并的肱骨远端骨折中进行了植入物移除,目的是改善肘部的运动范围。即使有适当的手术预防措施,解剖时尺神经受损。这份报告旨在深入了解这种罕见的现象,并对造成这种伤害的原因进行回顾性检查。操作说明的重要性,手术方法,神经的前部移位,这些因素和其他因素如何帮助外科医生避免这种并发症也得到了强调。
    Injuries to the ulnar nerve during open reduction and internal fixation of distal humerus fractures are a well-known phenomenon. However, ulnar nerve injury during implant removal has not been well documented. We performed implant removal in a united distal humerus fracture with the aim of improving the elbow\'s range of motion. Even with proper surgical precautions in place, the ulnar nerve was damaged during dissection. This report aims to provide insight into this rare phenomenon, and the reasons for this injury are examined retrospectively. The importance of operation notes, the surgical approach, anterior transposition of the nerve, and how this and other factors could have helped the surgeons avoid this complication have also been highlighted.
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  • 文章类型: Journal Article
    周围神经损伤很普遍,其治疗存在重大挑战。在各种重建方案中,神经导管和包裹是受欢迎的选择。生物工程和再生医学的进步导致了新的生物相容性材料和植入物设计的开发,这些材料和植入物设计提供了增强神经恢复的潜力。成本,神经损伤类型,在决定理想的重建方案时,必须考虑植入物的大小。
    Peripheral nerve injuries are prevalent and their treatments present significant challenges. Among the various reconstructive options, nerve conduits and wraps are popular choices. Advances in bioengineering and regenerative medicine have led to the development of new biocompatible materials and implant designs that offer the potential for enhanced neural recovery. Cost, nerve injury type, and implant size must be considered when deciding on the ideal reconstructive option.
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  • 文章类型: Journal Article
    周围神经损伤通常会导致运动和感觉障碍的症状,损伤后神经恢复缓慢,治疗方法有限,会加重症状,甚至导致终身残疾。姜黄素可以促进周围神经再生,但是如何在局部周围神经中准确递送适当浓度的姜黄素仍有待解决。在这项研究中,我们设计了一种人发角蛋白/壳聚糖(C/K)水凝胶,其具有交联的三聚磷酸钠离子以局部递送姜黄素。壳聚糖改善了水凝胶的机械性能,角蛋白改善了水凝胶的生物相容性。C/K水凝胶显示出良好的细胞相容性,组织相容性和降解性。体外实验表明,水凝胶可以连续释放姜黄素10天。此外,对行为的全面分析,电生理学,组织学,动物实验和靶器官恢复结果表明,除了水凝胶外,局部递送姜黄素还可以增强神经再生。总之,我们提供了一种结合人类头发角蛋白优点的新方法,壳聚糖,和姜黄素用于神经损伤修复。
    Peripheral nerve injury often leads to symptoms of motor and sensory impairment, and slow recovery of nerves after injury and limited treatment methods will aggravate symptoms or even lead to lifelong disability. Curcumin can promote peripheral nerve regeneration, but how to accurately deliver the appropriate concentration of curcumin in the local peripheral nerve remains to be solved. In this study, we designed a human hair keratin/chitosan (C/K) hydrogel with sodium tripolyphosphate ions crosslinked to deliver curcumin topically. Chitosan improves the mechanical properties of hydrogels and keratin improves the biocompatibility of hydrogels. C/K hydrogel showed good cytocompatibility, histocompatibility and degradability. In vitro experiments showed that hydrogels can continuously release curcumin for up to 10 days. In addition, a comprehensive analysis of behavioral, electrophysiological, histology, and target organ recovery results in animal experiments showed that locally delivered curcumin can enhance nerve regeneration in addition to hydrogels. In short, we provide a new method that combines the advantages of human hair keratin, chitosan, and curcumin for nerve damage repair.
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  • 文章类型: English Abstract
    Objective:To investigate the characteristics and prognosis of two anastomosis techniques in repairing facial nerve defects. Methods:A retrospective analysis was conducted on 30 patients who underwent facial nerve anastomosis(direct or rerouting) for facial nerve defects in our department from January 2012 to December 2021. Among them, 21 were male and 9 were female, with an average age of(37.53±11.33) years, all with unilateral onset. Preoperative House-Brackmann(H-B) facial nerve function grades were Ⅳ in 2 cases, Ⅴ in 9 cases, and Ⅵin 19 cases. The duration of facial paralysis before surgery was within 6 months in 21 cases, 6-12 months in 6 cases, and over 1 year in 3 cases. The causes of facial paralysis included 14 cases of cholesteatoma, 6 cases of facial neurioma, 6 cases of trauma, and 4 cases of middle ear surgery injury. Surgical approaches included 9 cases of the middle cranial fossa approach, 8 cases of labyrinthine-otic approach, 7 cases of mastoid-epitympanum approach, and 6 cases of retroauricular lateral neck approach. Results:All patients were followed up for more than 2 years. The direct anastomosis was performed in 10 cases: 6 cases with defects located in the extratemporal segment and 4 cases in the tympanic segment. Rerouting anastomosis was performed in 20 cases: 11 cases with defects located in the labyrinthine-geniculate ganglion, 4 cases from the internal auditory canal to the geniculate ganglion, 3 cases in the internal auditory canal, and 2 cases in the horizontal-pyramid segment. Postoperative H-B facial nerve grades were Ⅱ in 2 cases, Ⅲ in 20 cases, and Ⅳ in 8 cases, with 73.3%(22/30) of patients achieving H-B grade Ⅲ or better. Conclusion:Both direct and rerouting anastomosis techniques can effectively repair facial nerve defects, with no significant difference in efficacy between the two techniques. Most patients can achieve H-B grade Ⅲ or better facial nerve function recovery. Preoperative facial nerve function and duration of facial paralysis are the main prognostic factors affecting the outcome of facial nerve anastomosis.
    目的:探讨分析2种吻合术修复面神经缺损的疗效及影响因素。 方法:回顾性分析2012年1月至2021年12月在我科行面神经吻合术(直接或改道)修复面神经缺损的30例患者临床资料,其中男21例,女9例,平均年龄(37.53±11.33)岁,均为单侧发病;术前H-B Ⅳ级2例、Ⅴ级9例、Ⅵ级19例;面瘫患者术前面瘫时间6个月以内21例,6~12个月6例,1年以上3例;面瘫原因包括胆脂瘤14例、面神经肿瘤6例、外伤6例、中耳手术损伤4例。手术入路包括颅中窝入路9例,迷路-耳囊入路8例,乳突-上鼓室入路7例,耳后颈侧入路6例。 结果:随访2年以上。术中采用直接吻合10例:缺损位于颞骨外段6例,水平-锥段4例;改道吻合20例:缺损位于迷路-膝状神经节11例,内听道至膝状神经节及水平段近端4例,内听道3例,水平-锥段2例。术后H-B面神经评分为Ⅱ级2例、Ⅲ级20例、Ⅳ级8例,73.3%(22/30)患者能达到H-B Ⅲ级或更好。 结论:面神经直接吻合术和改道吻合术均可修复面神经缺损,2种术式疗效无明显差异。多数患者能达到H-B Ⅲ级或更好。术前面神经功能评级及术前面瘫时间是影响面神经吻合效果的主要影响因素。.
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  • 文章类型: Journal Article
    创伤或神经病导致的周围神经损伤(PNI)可导致严重的残疾,其预后随着年龄的增长而恶化。新的证据表明,肠道菌群失调和减少的粪便短链脂肪酸(SCFA)有助于年龄相关的全身性炎症(炎症),这阻碍了受伤后的神经恢复。因此,这项研究旨在评估使用老年小鼠在临床前PNI模型中恢复活力的粪便微生物群移植(FMT)的促再生作用。老年C57BL/6小鼠坐骨神经双侧挤压损伤。随后,他们要么在受伤后3天和4天接受来自年轻供体的FMT,要么保留了他们年老的肠道微生物群.我们分析了粪便样品中的肠道微生物组组成和SCFA浓度。通过Claudin-1的免疫荧光染色评估回肠粘膜屏障的完整性。流式细胞术用于检查回肠中的免疫细胞和细胞因子的产生,脾,脾和坐骨神经。各种评估,包括行为测试,电生理学研究,和形态计量学分析,进行评估周围神经功能和损伤后的修复。恢复FMT通过增加放线菌来逆转年龄相关的肠道菌群失调,尤其是双歧杆菌属。这种干预还导致老年受者肠道SCFA水平升高,并减轻了与年龄相关的回肠粘膜渗漏。此外,它增加了回肠和脾脏中的T辅助细胞2(Th2)和调节性T(Treg)细胞的数量,大多数人对抗炎白细胞介素-10(IL-10)呈阳性。在坐骨神经中,再生FMT导致M2巨噬细胞计数增加和IL-10+TNF-α-M2巨噬细胞亚群产生更高的IL-10。最终,在老年小鼠中恢复年轻的肠道微生物组导致PNI后神经修复改善和功能恢复增强。考虑到FMT已经是一种临床可用的技术,探索针对肠道微生物组的新型转化策略以增强老年人的神经修复似乎很有希望,值得进一步评估。
    Peripheral nerve injury (PNI) resulting from trauma or neuropathies can cause significant disability, and its prognosis deteriorates with age. Emerging evidence suggests that gut dysbiosis and reduced fecal short-chain fatty acids (SCFAs) contribute to an age-related systemic hyperinflammation (inflammaging), which hinders nerve recovery after injury. This study thus aimed to evaluate the pro-regenerative effects of a rejuvenating fecal microbiota transplant (FMT) in a preclinical PNI model using aged mice. Aged C57BL/6 mice underwent bilateral crush injuries to their sciatic nerves. Subsequently, they either received FMT from young donors at three and four days after the injury or retained their aged gut microbiota. We analyzed gut microbiome composition and SCFA concentrations in fecal samples. The integrity of the ileac mucosal barrier was assessed by immunofluorescence staining of Claudin-1. Flow cytometry was utilized to examine immune cells and cytokine production in the ileum, spleen, and sciatic nerve. Various assessments, including behavioural tests, electrophysiological studies, and morphometrical analyses, were conducted to evaluate peripheral nerve function and repair following injury. Rejuvenating FMT reversed age-related gut dysbiosis by increasing Actinobacteria, especially Bifidobacteriales genera. This intervention also led to an elevation of gut SCFA levels and mitigated age-related ileac mucosal leakiness in aged recipients. Additionally, it augmented the number of T-helper 2 (Th2) and regulatory T (Treg) cells in the ileum and spleen, with the majority being positive for anti-inflammatory interleukin-10 (IL-10). In sciatic nerves, rejuvenating FMT resulted in increased M2 macrophage counts and a higher IL-10 production by IL-10+TNF-α- M2 macrophage subsets. Ultimately, restoring a youthful gut microbiome in aged mice led to improved nerve repair and enhanced functional recovery after PNI. Considering that FMT is already a clinically available technique, exploring novel translational strategies targeting the gut microbiome to enhance nerve repair in the elderly seems promising and warrants further evaluation.
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  • 文章类型: Journal Article
    脂肪来源的干细胞(ADSC)是当今再生医学中利用最多的细胞之一。它们正在快速增长,能够增强轴突伸长,支持和局部刺激雪旺氏细胞(SC),并保护去神经支配的肌肉免受周围神经损伤后的萎缩。为了开发生物安全,临床上可翻译的细胞疗法,我们在体内大鼠模型中评估了用人血小板裂解物预扩增ADSC的效果,将细胞转移到15毫米的临界大小的坐骨神经缺损中,该缺损嵌入由聚已内酯(PCL)神经导管包裹的层粘连蛋白-肽功能化水凝胶(Biogelx-IKVAV)中。ADSC保留了他们的干劲,在体外测试时,它们的免疫表型和增殖活性。植入后6周,通过人ADSC-IKVAV填充的PCL导管内的轴突伸长(抗-NF200)和SC增殖(抗-S100)评估,在临界尺寸间隙观察到了强劲的再生.所有其他实验组表现出显著较低水平的生长锥伸长。组织学腓肠肌分析具有可比性,实验组之间没有定量显着差异。一起来看,这些结果表明,封装在Biogelx-IKVAV中的ADSC是提高神经再生疗效的潜在途径.可以为开发用于治疗周围神经损伤的全合成生物工程神经移植物寻求新的观点。
    Adipose-derived stem cells (ADSC) are nowadays one of the most exploited cells in regenerative medicine. They are fast growing, capable of enhancing axonal elongation, support and locally stimulate Schwann cells (SCs), and protect de-innervated muscles from atrophy after a peripheral nerve injury. With the aim of developing a bio-safe, clinically translatable cell-therapy, we assessed the effect of ADSC pre-expanded with human platelet lysate in an in vivo rat model, delivering the cells into a 15 mm critical-size sciatic nerve defect embedded within a laminin-peptide-functionalized hydrogel (Biogelx-IKVAV) wrapped by a poly-ɛ-caprolactone (PCL) nerve conduit. ADSC retained their stemness, their immunophenotype and proliferative activity when tested in vitro. At 6 weeks post-implantation, robust regeneration was observed across the critical-size gap as evaluated by both the axonal elongation (anti-NF 200) and SC proliferation (anti-S100) within the human ADSC-IKVAV filled PCL conduit. All the other experimental groups manifested significantly lower levels of growth cone elongation. The histological gastrocnemius muscle analysis was comparable with no quantitative significant differences among the experimental groups. Taken together, these results suggest that ADSC encapsulated in Biogelx-IKVAV are a potential path to improve the efficacy of nerve regeneration. New perspectives can be pursued for the development of a fully synthetic bioengineered nerve graft for the treatment of peripheral nerve injury.
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  • 文章类型: Journal Article
    由于功能恢复不良,周围神经病变的治疗仍然是一个主要挑战;因此,正在进行的研究努力,以加强周围神经修复。在这项研究中,我们旨在通过对嵌入纤维蛋白水凝胶中的施万细胞(SCs)进行机械刺激,建立Büngner构建体的三维组织工程条带.我们首次展示了菌株的应用诱导(i)类似于Büngner条带的SC的纵向排列,和(ii)通过BDNF的上调证明的明显修复SC表型的表达,NGF,和p75NTR。此外,我们表明,在与大鼠背根神经节外植体共培养模型中,机械排列的SCs为轴突在体外数毫米以上的迁移提供了物理指导.因此,这些构建体对移植到患者体内具有巨大的治疗潜力,也可能为药物筛选或病理或再生过程研究提供生理相关的体外周围神经模型.
    Treatment of peripheral nerve lesions remains a major challenge due to poor functional recovery; hence, ongoing research efforts strive to enhance peripheral nerve repair. In this study, we aimed to establish three-dimensional tissue-engineered bands of Büngner constructs by subjecting Schwann cells (SCs) embedded in fibrin hydrogels to mechanical stimulation. We show for the first time that the application of strain induces (i) longitudinal alignment of SCs resembling bands of Büngner, and (ii) the expression of a pronounced repair SC phenotype as evidenced by upregulation of BDNF, NGF, and p75NTR. Furthermore, we show that mechanically aligned SCs provide physical guidance for migrating axons over several millimeters in vitro in a co-culture model with rat dorsal root ganglion explants. Consequently, these constructs hold great therapeutic potential for transplantation into patients and might also provide a physiologically relevant in vitro peripheral nerve model for drug screening or investigation of pathologic or regenerative processes.
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  • 文章类型: Journal Article
    由于神经的再生能力有限,周围神经损伤是一种复杂而具有挑战性的医学疾病,导致感觉和运动功能的丧失。水凝胶已成为促进周围神经再生的有前途的生物材料,而传统的水凝胶通常由于有限的网络动力学而无法支持内源性细胞浸润,从而损害治疗结果。在这里,我们提出了一种细胞适应性的水凝胶,其中包含模拟组织的丝素蛋白网络和动态交联的双膦酸盐-藻酸盐网络。这种水凝胶的动态网络可以响应细胞产生的力进行细胞介导的重组,从而有效促进雪旺氏细胞和巨噬细胞的快速浸润,以及轴突的向内生长。我们进一步表明,从水凝胶中释放的镁离子不仅促进神经突生长,而且以顺序的方式调节巨噬细胞的极化,有助于形成再生微环境。因此,这种水凝胶可有效防止肌肉萎缩,并在8周内促进高达10毫米的神经缺损的再生和功能恢复。这项研究的结果表明,适应性水凝胶是有希望的诱导生物材料,用于增强周围神经损伤治疗的治疗效果。
    Peripheral nerve injury is a complex and challenging medical condition due to the limited ability of nerves to regenerate, resulting in the loss of both sensory and motor function. Hydrogels have emerged as a promising biomaterial for promoting peripheral nerve regeneration, while conventional hydrogels are generally unable to support endogenous cell infiltration due to limited network dynamics, thereby compromising the therapeutic outcomes. Herein, we present a cell adaptable hydrogel containing a tissue-mimetic silk fibroin network and a dynamically crosslinked bisphosphonated-alginate network. The dynamic network of this hydrogel can respond to cell-generated forces to undergo the cell-mediated reorganization, thereby effectively facilitating the rapid infiltration of Schwann cells and macrophages, as well as the ingrowth of axons. We further show that the magnesium ions released from the hydrogel not only promote neurite outgrowth but also regulate the polarization of macrophages in a sequential manner, contributing to the formation of a regenerative microenvironment. Therefore, this hydrogel effectively prevents muscle atrophy and promotes the regeneration and functional recovery of nerve defects of up to 10 mm within 8 weeks. The findings from this study demonstrate that adaptable hydrogels are promising inductive biomaterials for enhancing the therapeutic outcomes of peripheral nerve injury treatments.
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  • 文章类型: Journal Article
    神经导管是一种很有前途的治疗长间隙周围神经损伤,然而它的功效是有限的。可释放药物的支架可以提供可靠的平台来构建用于神经恢复的再生微环境。在这项研究中,通过用于促进神经再生的连续3D打印技术制造封装有前药纳米组件的弹性水凝胶导管。生物活性水凝胶由明胶甲基丙烯酰基(GelMA)和丝素蛋白甲基丙烯酸缩水甘油酯(SF-MA)组成,对附着力表现出积极的影响,扩散,和施万细胞的迁移。同时,具有高载药能力的7,8-二羟基黄酮(7,8-DHF)前药纳米组装体通过亲脂性前药的自组装来开发并加载到GelMA/SF-MA水凝胶中。载药导管可持续释放7,8-DHF以促进神经突伸长。通过手术缝合大鼠坐骨神经,建立了12mm神经缺损模型,用于评估治疗效果。电生理学,形态学,组织学评估表明,该导管可以促进轴突再生,髓鞘再生,和功能恢复通过提供一个有利的微环境。这些发现暗示具有7,8-DHF释放的GelMA/SF-MA导管在治疗长间隙周围神经损伤方面具有潜力。
    Nerve guide conduit is a promising treatment for long gap peripheral nerve injuries, yet its efficacy is limited. Drug-releasable scaffolds may provide reliable platforms to build a regenerative microenvironment for nerve recovery. In this study, an elastic hydrogel conduit encapsulating with prodrug nanoassemblies is fabricated by a continuous 3D printing technique for promoting nerve regeneration. The bioactive hydrogel is comprised of gelatin methacryloyl (GelMA) and silk fibroin glycidyl methacrylate (SF-MA), exhibiting positive effects on adhesion, proliferation, and migration of Schwann cells. Meanwhile, 7,8-dihydroxyflavone (7,8-DHF) prodrug nanoassemblies with high drug-loading capacities are developed through self-assembly of the lipophilic prodrug and loaded into the GelMA/SF-MA hydrogel. The drug loading conduit could sustainedly release 7,8-DHF to facilitate neurite elongation. A 12 ​mm nerve defect model is established for therapeutic efficiency evaluation by implanting the conduit through surgical suturing with rat sciatic nerve. The electrophysiological, morphological, and histological assessments indicate that this conduit can promote axon regeneration, remyelination, and function recovery by providing a favorable microenvironment. These findings implicate that the GelMA/SF-MA conduit with 7,8-DHF release has potentials in the treatment of long-gap peripheral nerve injury.
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  • 文章类型: Journal Article
    周围神经再生和功能恢复仍然是临床实践中的主要挑战。神经引导导管(NGC)可以调节再生微环境,有利于周围神经修复。富血小板血浆(PRP)可分泌多种生长因子调节再生微环境。然而,目前PRP的给药方法迅速激活,随后是生长因子的突释,导致体内治疗效率低。为了克服这些缺点,通过将PRP掺入明胶甲基丙烯酸酯(GelMA)和藻酸钠(SA)水凝胶中制造复合神经导管。GelMA/SA-3/PRP-20NGC具有最佳的机械性能,降解率,和优越的生物性能。重要的是,GelMA/SA-3/PRP-20NGC实现了两种主要生长因子的持续释放(VEGF-A,PDGF-BB)来自PRP。此外,GelMA/SA-3/PRP-20NGC在体外显着促进雪旺细胞的迁移和内皮细胞的新生血管形成。而桥接10毫米大鼠坐骨神经缺损,GelMA/SA-3/PRP-20NGC促进轴突再生和周围神经功能恢复。因此,GelMA/SA-3/PRP-20NGC可以通过PRP持续释放生长因子来调节再生微环境,为PRP在周围神经修复中的临床应用提供了新的思路。
    Peripheral nerve regeneration and functional recovery remain major challenges in clinical practice. Nerve guidance conduits (NGCs) which can regulate the regenerative microenvironment are beneficial for peripheral nerve repair. Platelet-rich plasma (PRP) can secrete multiple growth factors to regulate the regenerative microenvironment. However, current administration methods of PRP are rapidly activated followed by the burst release of growth factors, causing low therapeutic efficiency in vivo. To overcome these disadvantages, a composite nerve conduit was fabricated by incorporating PRP into a gelatin methacrylate (GelMA) and sodium alginate (SA) hydrogel. The GelMA/SA-3/PRP-20 NGCs possess optimal mechanical properties, degradation rate, and superior biological performance. Importantly, GelMA/SA-3/PRP-20 NGCs achieved the sustained release of two major growth factors (VEGF-A, PDGF-BB) from PRP. Moreover, the GelMA/SA-3/PRP-20 NGCs significantly promoted the migration of Schwann cells and the neovascularization of endothelial cells in vitro. While bridging 10 mm rat sciatic nerve defects, the GelMA/SA-3/PRP-20 NGCs promoted axonal regeneration and functional recovery of peripheral nerves. Therefore, the GelMA/SA-3/PRP-20 NGCs could regulate the regenerative microenvironment by sustained release of growth factors from PRP and shed new light on the clinical application of PRP in peripheral nerve repair.
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