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脱细胞神经同种异体移植物控制轴突再生可限制周围神经横断后神经瘤的形成:猪模型的实验研究。

Controlling axonal regeneration with acellular nerve allograft limits neuroma formation in peripheral nerve transection: An experimental study in a swine model.

机构信息

Regenerative Medicine Department, Naval Medical Research Center, Silver Spring, Maryland, USA.

Orthopaedics, Uniformed Services University of the Health Sciences-Walter Reed Department of Surgery, Bethesda, Maryland, USA.

出版信息

Microsurgery. 2022 Sep;42(6):603-610. doi: 10.1002/micr.30943. Epub 2022 Aug 4.

DOI:10.1002/micr.30943
PMID:35925036
Abstract

BACKGROUND

Symptomatic neuromata are a common indication for revision surgery following amputation. Previously described treatments, including traction neurectomy, nerve transposition, targeted muscle re-innervation, and nerve capping, have provided inconsistent results or are technically challenging. Prior research using acellular nerve allografts (ANA) has shown controlled termination of axonal regrowth in long grafts. The purpose of this study was to determine the ability of a long ANA to prevent neuroma formation following transection of a peripheral nerve in a swine model.

MATERIALS AND METHODS

Twenty-two adult female Yucatan miniature swine (Sus scrofa; 4-6 months, 15-25 kg) were assigned to control (ulnar nerve transection only, n = 10), treatment (ulnar transection and coaptation of 50 mm ANA, n = 10), or donor (n = 2) groups. Nerves harvested from donor group animals were treated to create the ANA. After 20 weeks, the transected nerves including any neuroma or graft were harvested. Both qualitative (nerve architecture, axonal sprouting) and quantitative histologic analyses (myelinated axon number, cross sectional area of nerve tissue) were performed.

RESULTS

Qualitative histologic analysis of control specimens revealed robust axon growth into dense scar tissue. In contrast, the treatment group revealed dwindling axons in the terminal tissue, consistent with attenuated neuroma formation. Quantitative analysis revealed a significantly decreased number of myelinated axons in the treatment group (1232 ± 540) compared to the control group (44,380 ± 7204) (p < .0001). Cross sectional area of nerve tissue was significantly smaller in treatment group (2.83 ± 1.53 mm ) compared to the control group (9.14 ± 1.19 mm ) (p = .0012).

CONCLUSIONS

Aberrant axonal growth is controlled to termination with coaptation of a 50 mm ANA in a swine model of nerve injury. These early results suggest further investigation of this technique to prevent and/or treat neuroma formation.

摘要

背景

症状性神经瘤是截肢后修复手术的常见指征。以前描述的治疗方法,包括牵引神经切除术、神经移位、靶向肌肉再神经支配和神经套囊,结果不一致或技术上具有挑战性。使用去细胞异体神经移植物 (ANA) 的先前研究表明,在长移植物中可控制轴突再生的终止。本研究的目的是确定长 ANA 在猪模型中阻断周围神经横断后神经瘤形成的能力。

材料和方法

22 只成年雌性尤卡坦微型猪(Sus scrofa;4-6 个月,15-25kg)分为对照组(仅尺神经横断,n=10)、治疗组(尺神经横断和 50mm ANA 吻合,n=10)或供体组(n=2)。从供体组动物中取出的神经进行处理以制备 ANA。20 周后,收获横断神经,包括任何神经瘤或移植物。进行定性(神经结构、轴突发芽)和定量组织学分析(有髓轴突数量、神经组织横截面积)。

结果

对照组标本的定性组织学分析显示,大量轴突生长到致密的瘢痕组织中。相比之下,治疗组在末端组织中发现轴突减少,与神经瘤形成减弱一致。定量分析显示,治疗组的有髓轴突数量明显减少(1232±540),而对照组(44380±7204)(p<0.0001)。治疗组神经组织的横截面积明显较小(2.83±1.53mm),而对照组(9.14±1.19mm)(p=0.0012)。

结论

在猪神经损伤模型中,与 50mm ANA 吻合可控制异常轴突生长至终止。这些早期结果表明进一步研究该技术以预防和/或治疗神经瘤形成。

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引用本文的文献

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Neuromas cause severe residual problems at long-term despite surgery.神经瘤即使经过手术,仍会导致长期严重的残留问题。
Sci Rep. 2023 Sep 21;13(1):15693. doi: 10.1038/s41598-023-42245-4.