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.

项目摘要：为了使截肢者探索具有快速移动控制的最先进的假肢的全部能力和高度的能力分辨率感知感，是一个有大量可靠和独立通道的神经接口，需要感官信息。神经中的强信号源是Ranvier的节点，本质上是在小3-D体积中随机分布。为了全面参与神经的电活动，神经元界面应以相同尺度的3-D体积询问神经。迄今为止，临床翻译性，所有现有神经间接位置的性能和/或操作寿命都是：限于低频道计数和/或非-3-D电极布置，能够仅在非常低的信号放大器下检测单单元活性被噪音淹没，和/或触发与随时间降低的通道性能相关的外国身体响应。我们的 3-D可伸缩神经界面的范式转移方法是整合一堆多电极薄膜聚酰亚胺 - 金属电极阵列（“螺纹”）进入组织工程生物降解的基于细胞外基质的水凝胶神经脚手架。我们称这类新的神经界面组织工程电子神经界面（TEENI）。初步研究表明，我们可以（1）可在高 - 可以存活高的多电极阵列温度反应性加速衰老（RAA）通过使用无定形硅和钛浸泡测试金属和聚酰亚胺层之间的粘附层，（2）通过整合一堆堆栈形成3-D电子的电子阵列聚合物 - 金属多电极阵列中的细胞外基质水凝胶支架，该水凝胶支架用小智慧包裹粘膜（SIS）支撑水凝胶，提供可缝合的末端以固定在神经上，并促进轻松手术处理和植入而不限制电极阵列的设计或损坏它，（3）实现强大的脉管系统和神经纤维的再生到TEENI支架中，（4）获得了单单元的慢性记录 Teeni内部的活动。但是，我们进行了两个观察结果，使该提案的具体目标融合在一起。首先，我们观察到每个螺纹周围的紧密组织反应，这可能会限制3-D TEENI多的密度电极线程集成。其次，我们观察到只有一部分再生神经组织优选生长沿着微制造的多电极阵列，其余的沿SIS包裹的内表面生长两者之间的水凝胶不完全降解。在特定目标1中，我们建议减少外国的大小人体反应以植入脑组织的微作业问题相同的方式相同：减少植入物的宽度和厚度分别为〜10 µm和〜1 µm。在特定目标2中，我们建议使用微通道图的水凝胶增加了轴突和雪旺氏细胞的数量和均匀性 TEENI微型制造的多电极阵列。为了对Teenis表现的独特见解，我们将可视化电子，节点，轴突，脉管系统的3-D分布以及内部界面周围的任何组织反应通过采用装置捕获的组织学，清晰度和光片显微镜，通过使用设备捕获的组织来再生神经。

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

Tissue-Engineered Peripheral Nerve Interfaces.

DOI：
10.1002/adfm.201701713
发表时间：
2018-03-21
期刊：
Advanced functional materials
影响因子：
19
作者：
Spearman, Benjamin S;Desai, Vidhi H;Schmidt, Christine E
通讯作者：
Schmidt, Christine E

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

Integration of flexible polyimide arrays into soft extracellular matrix-based hydrogel materials for a tissue-engineered electronic nerve interface (TEENI).