Name: fabrication of the composite regenerative peripheral nerve interface (c-rpni) in the adult rat
Uploaded: 2020-02-25T13:00:00
Description: Watch this Scientific Journal Video about Fabrication of the Composite Regenerative Peripheral Nerve Interface C-RPNI in the Adult Rat at JoVE.com

作者感谢Jana Moon提供专家技术援助。本文中提出的研究由R21（R21NS104584）赠款资助SK。

所有动物实验均经密歇根大学动物使用和护理委员会批准进行。
注：在皮肤和肌肉捐赠程序之前，允许捐赠大鼠免费获得食物和水。安乐死是在深度麻醉下进行的，然后用双边肺气肿的辅助方法注射心脏内氯化钾。任何大鼠菌株理论上都可以用于本实验;然而，我们的实验室在2至4个月大时，在雄性和雌性费舍尔F344大鼠（+200-250g）中取得了一致的结果。捐赠大鼠必须与实验鼠?...

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C-RPNI 是一种新颖的结构，它提供目标神经的运动信号同时放大，并提供一种可菲的感官反馈。特别是，C-RPNI对于近肢截肢患者具有独特的效用，因为他们的运动和感觉分节在手术过程中不易机械分离。相反，C-RPNI利用神经本身固有的优先再内生特性，鼓励感觉纤维再生到皮肤感觉末端器官和运动纤维到神经肌肉结。
由于C-RPNI制造依赖于目标神经的再内化能力，因此在手术过?...

截肢影响近190个美国人1，其患病率预计将从现在的160万增加到超过360万到2050年2。尽管有文件记载使用超过一千年，理想的假肢尚未实现3。目前，存在复杂的假肢，能够进行多个关节操作，有可能再现原生四肢4、5的许多运动功能。但是，这些设备不被视为直观，因为所需的假肢运动通常与输入控制信号在功能上是分开的。用户通常认为这些"高级假肢"难以学习，因此不适合日常使用1，6。此外，目前市场上的复杂假肢不能提供任何明显程度的细微感官反馈，以进行适当的控制。触觉和自我感知对于执行日常任务至关重要，如果没有这些，简单的行为，如拿起一杯咖啡，就会变得很麻烦，因为它完全依赖于视觉线索7，8，9。由于这些原因，先进的假肢与相当程度的精神疲劳有关，并经常被描述为负担和不满意5，10，11。为了解决这个问题，一些研究实验室已经开发出了能够通过直接神经相互作用12、13、14、15提供有限程度感官反馈的假肢，但反馈往往仅限于手和手指上的微小、分散的区域12、13，并且感觉有时15次是痛苦和不自然的。不幸的是，这些研究中有许多缺乏任何明显的长期随访和神经组织学来划定局部组织效应，同时指出界面衰竭的规模为周到月16。
对于这些人群，理想的假肢装置将提供高保真运动控制，以及个人在其一生中从个人环境中获得有意义的躯体感官反馈。对于上述理想假肢的设计来说，关键是开发一个稳定、可靠的接口，允许同时传输具有有效运动信号的体感信息。目前最有希望的人机界面是那些直接与周围神经系统相互作用的界面，而神经集成假肢领域的最新发展有助于弥合生物电和机械信号之间的差距。目前使用的接口包括：柔性神经板14，15，18，神经外袖口电极13，19，20，21，22，23，组织穿透电极24，25，31，32，和宫内电极26，27 ， 28.然而，这些方法中的每一个都显示出神经特异性、组织损伤、斧子退化、骨髓消耗和/或疤痕组织形成与慢性外体反应相关的局限性16、17、18、19。最近，人们推测，最终植入电极故障背后的驱动因素是杨的调制在电子材料和原生神经组织之间的显著差异。脑组织每天受到显著的微运动的影响，据推测，由杨的月色差异引起的剪切应力会引起炎症，并最终造成永久性疤痕30，31，32。这种效应经常在四肢中复合，在四肢，周围神经受到生理微运动和故意四肢宏观运动的影响。由于这种恒定的运动，可以合理地得出结论，使用完全非生物的外周神经界面并不理想，并且与生物成分的接口将更合适。
为了满足对生物成分的需求，我们的实验室开发了一种生物神经界面，称为再生外周神经接口 （RPNI），将残肢中的外端外周神经与假肢装置集成。RPNI的制造包括手术将外周神经植入自体自由肌肉移植物中，随后再血管化和再生。我们的实验室在过去十年中开发了这种生物神经界面，在动物和人体试验中与植入的电极结合时，成功地放大和传输运动信号，从而可以进行具有多重自由度的适当假肢控制。此外，我们分别演示了感官反馈，通过使用外周神经嵌入在皮肤移植，称为皮肤感官接口（DSI）3，35 。在较远端截肢时，同时使用这些构造是可行的，因为目标周围神经内的马达和感觉分节可以手术分离。然而，对于更近的截肢，由于运动和感觉纤维的混用，这是不可行的。复合再生外周神经接口（C-RPNI）是为更近的截肢而开发的，它涉及将混合感觉运动神经植入由自由肌肉移植物组成的结构中（图1）。外周神经表现出优先靶向的再生，因此感觉纤维将重新内层皮肤移植和运动纤维，肌肉移植。因此，这种结构能够同时放大运动信号，同时提供躯体感官反馈36（图2），允许实现理想，直观，复杂的假肢。

<table border="1" fo:keep-together.within-page="1" fo:keep-with-next.within-page="always">
	<tbody>
		<tr>
			<td>#15 Scalpel</td>
			<td>Aspen Surgical, Inc</td>
			<td>Ref 371115</td>
			<td>Rib-Back Carbon Steel Surgical Blades (#15)</td>
		</tr>
		<tr>
			<td>4-0 Chromic Suture</td>
			<td>Ethicon</td>
			<td>SKU# 1654G</td>
			<td>P-3 Reverse Cutting Needle</td>
		</tr>
		<tr>
			<td>5-0 Chromic Suture</td>
			<td>Ethicon</td>
			<td>SKU# 687G</td>
			<td>P-3 Reverse Cutting Needle</td>
		</tr>
		<tr>
			<td>6-0 Ethilon Suture</td>
			<td>Ethicon</td>
			<td>SKU# 697G</td>
			<td>P-1 Reverse Cutting Needle (Nylon suture)</td>
		</tr>
		<tr>
			<td>8-0 Monofilament Suture</td>
			<td>AROSurgical</td>
			<td>T06A08N14-13</td>
			<td>Black polyamide monofilament suture on a threaded tapered needle</td>
		</tr>
		<tr>
			<td>Experimental Rats</td>
			<td>Envigo</td>
			<td>F344-NH-sd</td>
			<td>Rats are Fischer F344 Strain</td>
		</tr>
		<tr>
			<td>Fluriso (Isofluorane)</td>
			<td>VetOne</td>
			<td>13985-528-40</td>
			<td>Inhalational Anesthetic</td>
		</tr>
		<tr>
			<td>Micro Motor High Speed Drill with Stone</td>
			<td>Master Mechanic</td>
			<td>Model 151369</td>
			<td>Handheld rotary tool; kit comes with multiple fine grit stones</td>
		</tr>
		<tr>
			<td>Oxygen</td>
			<td>Cryogenic Gases</td>
			<td>UN1072</td>
			<td>Standard medical grade oxygen canisters</td>
		</tr>
		<tr>
			<td>Potassium Chloride</td>
			<td>APP Pharmaceuticals</td>
			<td>63323-965-20</td>
			<td>Injectable form, 2 mEq/mL</td>
		</tr>
		<tr>
			<td>Povidone Iodine USP</td>
			<td>MediChoice</td>
			<td>65517-0009-1</td>
			<td>10% Topical Solution, can use one bottle for multiple surgical preps</td>
		</tr>
		<tr>
			<td>Puralube Vet Opthalmic Ointment</td>
			<td>Dechra</td>
			<td>17033-211-38</td>
			<td>Corneal protective ointment for use during procedure</td>
		</tr>
		<tr>
			<td>Rimadyl (Caprofen)</td>
			<td>Zoetis, Inc.</td>
			<td>NADA# 141-199</td>
			<td>Injectable form, 50 mg/mL</td>
		</tr>
		<tr>
			<td>Stereo Microscope</td>
			<td>Leica</td>
			<td>Model M60</td>
			<td>User can adjust magnification to their preference</td>
		</tr>
		<tr>
			<td>Surgical Instruments</td>
			<td>Fine Science Tools</td>
			<td>Various</td>
			<td>User can choose instruments according to personal preference or from what is currently available in their lab</td>
		</tr>
		<tr>
			<td>Triple Antibiotic Ointment</td>
			<td>MediChoice</td>
			<td>39892-0830-2</td>
			<td>Ointment comes in sterile, disposable packets</td>
		</tr>
		<tr>
			<td>VaporStick 3</td>
			<td>Surgivet</td>
			<td>V7015</td>
			<td>Anesthesia tower with space for isofluorane and oxygen canister</td>
		</tr>
		<tr>
			<td>Webcol Alcohol Prep</td>
			<td>Coviden</td>
			<td>Ref 6818</td>
			<td>Alcohol prep wipes; use a new wipe for each prep</td>
		</tr>
	</tbody>
</table>

fabrication of the composite regenerative peripheral nerve interface (c-rpni) in the adult rat

神经假体的最新进展使那些患有肢体损失的人能够复制许多原生在缺失的四肢上的功能，这通常是通过与周围神经系统的整合来实现的。不幸的是，目前使用的方法往往与严重的组织损伤有关，防止长期使用。此外，这些设备通常缺乏任何有意义的感官反馈，因为他们复杂的结构抑制任何振动或其他感觉，用户以前可能依赖于使用更简单的假肢。复合再生外周神经接口 （C-RPNI） 是作为一种稳定的生物结构开发的，能够放大运动神经信号，同时提供同时的感官反馈。C-RPNI 由一段自由皮肤和肌肉移植组成，这些移植物固定在目标混合感觉运动神经周围，优先运动神经内移植肌肉移植和皮肤移植的感官神经内移植。在大鼠中，这种构造证明了复合肌肉作用电位（CMAP）的生成，将目标神经的信号从微伏到毫伏水平放大，信号噪声比平均约为30-50。刺激结构的皮肤组分在近端神经产生复合感觉神经作用电位（CSNAP）。因此，这种结构有广阔的未来效用，以实现理想，直观的假肢。

如果大鼠出现感染或无法经手术麻醉存活，构造制造被认为是不成功的。先前的研究表明，这些构造需要大约三个月的时间来重新血管化和再血管化2，3，17，36。在三个月的恢复期之后，可以进行构造测试以检查可行性。三个月后的手术暴露将揭示血管化的肌肉和皮肤，如果?...

Watch this Scientific Journal Video about Fabrication of the Composite Regenerative Peripheral Nerve Interface C-RPNI in the Adult Rat at JoVE.com

Fabrication of the Composite Regenerative Peripheral Nerve Interface C-RPNI in the Adult Rat

以下手稿描述了开发一种称为复合再生外周神经接口 （C-RPNI） 的生物、闭环神经反馈系统的新方法。这种结构能够与外围神经集成，以放大运动信号，同时提供一个信号反馈。

成年大鼠复合再生外周神经接口（C-RPNI）的制造

Recent advances in neuroprosthetics have enabled those living with extremity loss to reproduce many functions native to the absent extremity, and this is ...

我们的协议是重要的，因为它允许同时运动神经信号放大，同时提供一个可发性感觉神经刺激，通过利用生物周边神经接口。由于C-RPNI允许在同一外周神经接口内同时进行运动控制和感官反馈，因此该技术可以为截肢者提供一种与生命相同的假肢装置。许多患有截肢的人放弃先进的神经假肢设备，因为这些设备缺乏直观的控制力和有意义的感官反馈。这种技术提供，并可以防止假肢装置被遗弃。这种技术可以应用于四肢虚弱或缺失或感觉缺陷的个人，从而进一步洞察提供精确和直观的四肢控制的反馈系统。对周围神经进行手术是困难的，因为几乎没有出错的余地。使用高质量的乐器和经常练习是确保成功的最佳方法。手术技术是令人难以置信的难以传达和学习的文学形式。观察构造制造中涉及的每个步骤是掌握该方法的关键。为了准备皮肤移植，在确认对手趾捏没有反应后，在麻醉大鼠的眼睛上涂抹软膏。使用剪子，剃掉整个下背部、脚踝区域和爪子的侧面。使用顺序酒精碘酮溶液和酒精清洗，在爪子的植物表面对选定的后肢进行消毒。使用手持式微型电机高速钻头与可拆卸的圆形细砂砾抛光石，毛刺爪子的植物表面，以每分钟4000转的速度去除表皮应用盐水滴，以便不灼伤皮肤。潜在的真皮将有一个闪亮的外观与精确出血。在下肢涂抹一个图尼克，以减缓血液流动，并使用编号15手术刀，以尖锐地去除植物性皮肤。将皮肤放在盐水湿润的纱布中，以防止干燥，并在出血的脚上涂抹纱布，以减缓出血。将皮肤置于解剖显微镜下，并使用显微切口从皮肤移植的深层去除任何肌腱和结缔组织。变薄的皮肤移植物应稍微不透明，只包含真皮，尺寸约为0.5倍1厘米。然后将组织放入一个新的盐水湿润纱布，直到构造制造。要准备肌肉移植，使用数字15手术刀，使纵向切口沿下背部的前部，从刚刚在脚踝上方到膝盖以下。通过皮下组织解剖，暴露底层肌肉。在切口的开脱方面，暴露下肢肌肉的肌腱插入。头骨前是典型的最大和最前部的肌肉。就在这个肌肉的下面和后部是外侧数字耳长。要将远方的外向数字肌腱与该区域中的其他肌腱分离，请在肌腱下方插入钳子的两个叮当，并打开钳子以施加向上压力，从而引起肌腱偏移。肌腱的操纵应导致所有趾同时伸展。使用锋利的虹膜剪刀进行远近肌切除术，并使用十倍钝化分离肌肉与周围组织工作近，以找到肌腱的起源。一旦近向肌腱可以可视化，使用虹膜剪刀执行第二个十分切除术，并将肌肉移植物放在盐水湿润的纱布中。为了隔离和准备常见的佩罗内神经，剃一条大腿，用连续的酒精-贝塔丁-酒精清洗消毒暴露的皮肤。将麻醉大鼠放在手术显微镜下的加热垫上，将切口从离骨到坐骨切口，标记到膝盖的劣质部分，并倾斜远离股骨。然后使用数字15手术刀，通过基础二头肌股筋膜沿着标记切口。仔细解剖通过二头肌股肌肌肉到二头肌股骨下的空间。在识别普通佩罗内神经后，使用微细尖钳和微切口仔细分离普通每发神经与其他坐骨神经分支。在神经穿过膝盖表面时，用一对微切口将神经急剧地穿过，从而去除任何挥之不去的结缔组织。然后小心地将剩余的结缔组织从常见的过骨神经中释放，并近近释放神经，使神经的长度约为两厘米。神经是微妙的，轻微的失误可能会导致持久的功能缺陷。频繁的练习、精确的手术器械以及理想的手部定位和支持是掌握这项技术的关键。要制造C-RPNI结构，将肌肉移植物置于解剖显微镜下，并去除所有中央肌腱组织以及一小部分表皮，使肌腱末端完好无损。使用 8-0尼龙缝合线和两个中断的缝合线，固定普通佩罗内神经的横越端的表膜到肌肉移植区域，在神经的两侧没有表皮。用单个 6-0 尼龙中断缝合，将肌肉移植到股骨上，同时将神经肌肉结对向远离股骨的神经肌肉结。放置 8 - 0尼龙缝合在肌肉移植的劣质中心边缘的表皮，固定它到常见的佩罗内神经肾上腺素，从而在肌肉移植内的神经中产生松弛。将皮肤移植物放在肌肉移植物上，以便它完全覆盖神经和大部分肌肉，真皮的深层边缘停留在肌肉上。修剪任何超出肌肉边界并使用 8-0 的真皮尼龙中断缝合线，以周长固定皮肤移植到肌肉移植。用 5-0 色谱缝合以跑步方式关闭二头肌筋膜，并在运行方式中用 4-0 色缝合关闭覆盖皮肤。然后用酒精垫交换手术区，并应用抗生素软膏，然后让大鼠与独立于笼友的食物和水源进行恢复，并监测直至完全卧发。如果成功，手术后的构造暴露三个月后将揭示重新血管化的肌肉和皮肤和轻轻挤压常见的过关节神经与钳子近向构造将导致可见的肌肉收缩。组织学分析应证明可行的皮肤、神经和肌肉。免疫性也分别会揭示运动和感觉神经对神经肌肉结和感觉端器官的再内向。如所示，可以在体内这些构造上进行电生理测试，例如在 C-RPNI 制造后三个月和九个月进行。在这里，以图形格式显示单和总结复合肌肉作用潜力和复合感觉神经作用潜力在电生理测试中获得的信号。肌肉移植的不理想结果由缺乏特征复合肌肉作用潜在波形的衰减信号表示。皮肤分量水平的次优结果通常涉及波形的阻尼，具有显著的背景噪声。高质量的仪器至关重要。剪刀应锋利，钳子应细翻，以方便极其精确地处理皮肤移植物和神经，而不会造成伤害。经过制造，该方法可用于电生理学研究，以进一步描述信号功能，从而更深入地了解发泡和发向反馈回路。虽然C-RPNI允许感官反馈，但尚不清楚是否可以建立闭环反馈系统进行自我感知。我们目前正在实验室中解决这个问题。

Research

JoVE Journal

Bioengineering

Fabrication of the Composite Regenerative Peripheral Nerve Interface (C-RPNI) in the Adult Rat

Fabrication of Electrochemical-DNA Biosensors for the Reagentless Detection of Nucleic Acids, Proteins and Small Molecules

无试剂检测核酸，蛋白质和小分子的电化学DNA生物传感器的制备

As medicine is currently practiced, doctors send specimens to a central laboratory for testing and thus must wait hours or days to 
receive the results. ...

科研

生物工程

Bridging the Bio-Electronic Interface with Biofabrication

生物电子界面衔接与Biofabrication

Advancements in lab-on-a-chip technology promise to revolutionize both research and medicine through lower costs, better sensitivity, portability, and ...

Generation of a Three-dimensional Full Thickness Skin Equivalent and Automated Wounding

三维全层皮肤的生成等效和自动伤人

In vitro models are a cost effective and ethical alternative to study cutaneous wound healing processes. Moreover, by using human cells, these models ...

Design and Fabrication of an Elastomeric Unit for Soft Modular Robots in Minimally Invasive Surgery

设计和弹性股软模块化机器人微创手术制造

In recent years, soft robotics technologies have aroused increasing interest in the medical field due to their intrinsically safe interaction in ...

Methods for the Self-integration of Megamolecular Biopolymers on the Drying Air-LC Interface

对干燥空气-LC接口Megamolecular生物大分子的自我整合方法

Living organisms that use water are always prone to drying in the environment. Their activities are driven by biopolymer-based micro- and ...

Fabrication of Extracellular Matrix-derived Foams and Microcarriers as Tissue-specific Cell Culture and Delivery Platforms

细胞外基质衍生的泡沫和微载体如组织特异性细胞培养和交付平台的制造

Cell function is mediated by interactions with the extracellular matrix (ECM), which has complex tissue-specific composition and architecture. The focus ...

An Ultrasonic Tool for Nerve Conduction Block in Diabetic Rat Models

糖尿病大鼠模型神经传导阻滞的超声工具

Nerve conduction block with a high intensity-focused ultrasound (HIFU) transducer has been performed in normal and diabetic animal models recently. HIFU ...

Fabrication of Decellularized Cartilage-derived Matrix Scaffolds

脱碳软骨衍生基质支架的制备

Osteochondral defects lack sufficient intrinsic repair capacity to regenerate functionally sound bone and cartilage tissue. To this extent, cartilage ...

A Tripeptide-Stabilized Nanoemulsion of Oleic Acid

一种三肽稳定的油酸纳米乳液

We describe a method to produce a nanoemulsion composed of an oleic acids-Pt(II) core and a lysine-tyrosine-phenylalanine (KYF) coating (KYF-Pt-NE). The ...

The Fabrication and Operation of a Continuous Flow, Micro-Electroporation System with Permeabilization Detection

Current therapeutic innovations, such as CAR-T cell therapy, are heavily reliant on viral-mediated gene delivery. Although efficient, this technique is ...