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The Tissue-Engineered Electronic Nerve Interface (TEENI)

组织工程电子神经接口 (TEENI)

基本信息

批准号：
10402785
负责人：
Jack W Judy
金额：
$ 58.67万
依托单位：
UNIVERSITY OF FLORIDA
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-04-15 至 2024-10-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10402785
关键词：
3-Dimensional Action Potentials Adhesions Adverse effects Aging Amputation Amputees Axon Basal lamina Biological Markers Brain Caliber Cellular Assay Cellular Morphology Charge Chronic Cicatrix Data Dependence Devices Dimensions Electrodes Electrophysiology (science)Engineering Environment Extracellular Matrix Fiber Film Foreign Bodies Formulation Foundations Freedom Geometry Goals Hand High temperature of physical object Histologic Histology Human Hydrogels Hydrogen Peroxide Implant In Vitro Length Light Limb Prosthesis Limb structure Link Magnetism Mechanics Metals Methods Microelectrodes Microscopy Mission Modeling Motor Movement Natural regeneration Nerve Nerve Fibers Nerve Regeneration Nerve Tissue Neurons Noise Operative Surgical Procedures Pathway interactions Performance Peripheral Nerves Phase Polymers Population Process Property Protocols documentation Quality of life Ranvier&apos s Nodes Rattus Reporting Research Resolution Sampling Schwann Cells Sensory Sensory Receptors Signal Transduction Small Intestinal Submucosa Source Spinal Ganglia Surface Surgical sutures System Technology Testing Thick Thinness Time Tissue Engineering Tissues Titanium United States National Institutes of Health Width arm movement axon regeneration base biocompatible polymer brain tissue capsule cell motility clinically translatable cost crosslink density design disability electric impedance experimental study hydrogel scaffold implantation improved in vivo insight microdevice multi-electrode arrays regenerative regenerative tissue relating to nervous system response scaffold sciatic nerve silicon carbide

项目摘要

PROJECT SUMMARY: For amputees to exploit the full capability of state-of-the-art prosthetic limbs with rapid fine-movement control and high- resolution sensory percepts, a nerve-interface with a large number of reliable and independent channels of motor and sensory information is needed. The strongest signal sources in nerves are the nodes of Ranvier, which are essentially distributed randomly within a small 3-D volume. Thus, to comprehensively engage with the electrical activity of a nerve, a neural interface should interrogate a nerve in a 3-D volume of the same scale. To date, the clinical translatability, performance, and/or operational lifetime of all existing nerve-interfaces are either: limited to low channel counts and/or non-3-D electrode arrangements, capable of detecting single-unit activity at only very low signal amplitudes that are often swamped by noise, and/or trigger a foreign body response linked to diminished channel performance over time. Our paradigm-shifting approach for 3-D scalable nerve interfaces is to integrate a stack of multi-electrode thin-film polyimide- metal electrode arrays (“threads”) into tissue-engineered biodegradable extracellular-matrix-based hydrogel nerve scaffold. We call this new class of neural interface Tissue-Engineered Electronic Nerve Interfaces (TEENI). In preliminary studies we demonstrated that we can (1) microfabricate multi-electrode arrays that can survive high- temperature reactive-accelerated aging (RAA) soak tests through the use of amorphous silicon-carbide and titanium adhesion layers between the metal and polyimide layers, (2) form a 3-D array of electrodes by integrating a stack of polymer-metal multi-electrode arrays into an extracellular-matrix-based hydrogel scaffold wrapped with small-intestinal submucosa (SIS) to support the hydrogel, provide suturable ends for attachment to the nerve, and facilitate easy surgical handling and implantation without limiting the design of the electrode array or damaging it, (3) achieve robust regeneration of vasculature and neural fibers into the TEENI scaffold, and (4) obtain chronic recordings of single-unit activity inside TEENI implants. However, we made two observations that motivated the specific aims for this proposal. First, we observed a tight tissue response around each thread that that could limit the density of 3-D TEENI multi- electrode-thread integration. Second, we observed that only a fraction of the regenerated nerve tissue preferentially grew along the microfabricated multi-electrode arrays, with the remainder growing along the inner surface of the SIS wrap and with incompletely degraded hydrogel between the two. In Specific Aim 1 we propose to reduce the size of the foreign body response in the same manner it has been achieved with microfabricated probes implanted into brain tissue: reduce the width and thickness of the implant to ~10 µm and ~1 µm respectively. In Specific Aim 2 we propose to use microchannel-templated hydrogels to increase the number and uniformity of axons and Schwann cells regenerating near the TEENI microfabricated multi-electrode arrays. To gain unique insight into the performance of TEENIs, we will visualize the 3-D distribution of electrodes, nodes, axons, vasculature, and any tissue response around the interface inside the regenerated nerve by employing device-capture histology, CLARITY, and light sheet microscopy.

项目总结：为了让截肢者充分发挥最先进的假肢的能力，具有快速精细的运动控制和高度的分辨率感官知觉，具有大量可靠和独立的运动和需要感官信息。神经中最强的信号源是兰维尔的节点，它本质上是随机分布在一个很小的3-D体积内。因此，要全面参与神经的电活动，神经接口应该在相同规模的3-D体积中询问神经。到目前为止，临床可译性，所有现有神经接口的性能和/或工作寿命是：仅限于低通道数和/或非3-D电极配置，能够在非常低的信号幅度下检测单个单元的活动，而通常被噪声淹没，和/或触发异物反应，随着时间的推移，通道性能降低。我们的用于三维可伸缩神经接口的范式转换方法是集成一堆多电极薄膜聚酰亚胺- 金属电极阵列(线)植入组织工程可降解细胞外基质水凝胶神经脚手架。我们称这种新型神经接口为组织工程电子神经接口(Teeni)。在……里面初步研究表明，我们可以(1)微制造能够在高温下存活的多电极阵列。利用非晶态碳化硅和钛进行温度反应加速老化(RAA)浸泡试验金属和聚酰亚胺层之间的粘合层，(2)通过整合堆叠的聚合物-金属多电极阵列包裹小肠的细胞外基质水凝胶支架粘膜下层(SIS)支持水凝胶，提供可缝合的末端以连接到神经，并便于手术在不限制电极阵列的设计或损坏电极阵列的情况下处理和植入，(3)实现健壮血管系统和神经纤维在Teeni支架中的再生，以及(4)获得单个单位的慢性记录 Teeni植入物内部的活动。然而，我们提出了两点意见，推动了这项提案的具体目标。首先，我们观察到每根线周围有一种紧密的组织反应，这可能会限制3D Teeni多发血管的密度。电极丝一体化。其次，我们观察到只有一小部分再生的神经组织优先生长沿着微制造的多电极阵列，其余的沿着SIS包裹的内表面生长，并且两者之间有不完全降解的水凝胶。在具体目标1中，我们建议减少外国公司的规模身体反应的方式与植入脑组织的微型探针相同：减少种植体的宽度和厚度分别为~10微米和~1微米。在具体目标2中，我们建议使用微通道模板化水凝胶增加轴突和雪旺细胞再生的数量和一致性 Teeni微型制造的多电极阵列。为了对TEENI的表现有独到的见解，我们将可视化电极、结节、轴突、血管系统和内部界面周围的任何组织反应的三维分布通过使用设备捕获组织学、清晰度和光片显微镜观察再生神经。

项目成果

期刊论文数量（8）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

in vitro Reactive-Accelerated-Aging (RAA) Assessment of Tissue-Engineered Electronic Nerve Interfaces (TEENI).

DOI：
10.1109/embc.2018.8513458
发表时间：
2018-07
期刊：
Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual International Conference
影响因子：
0
作者：
Kuliasha CA;Judy JW
通讯作者：
Judy JW

Microtopographical patterns promote different responses in fibroblasts and Schwann cells: A possible feature for neural implants.

DOI：
10.1002/jbm.a.37007
发表时间：
2021-01
期刊：
Journal of biomedical materials research. Part A
影响因子：
0
作者：
Mobini S;Kuliasha CA;Siders ZA;Bohmann NA;Jamal SM;Judy JW;Schmidt CE;Brennan AB
通讯作者：
Brennan AB

Tissue-Engineered Peripheral Nerve Interfaces.