Direct integration of cortical electrodes by conducting polymers deposited in-viv

通过体内沉积的导电聚合物直接集成皮质电极

• 批准号: 8272576
• 负责人: DAVID C MARTIN
• 金额: $ 26.47万
• 依托单位: UNIVERSITY OF DELAWARE
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-06-01 至 2014-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8272576
• 关键词: Anti-Inflammatory Agents; Artificial cardiac pacemaker; Astrocytes; Attention; Cell Survival; Cell physiology; Cells; Charge; Cicatrix; Cochlear Implants; Communication; Deposition; Development; Devices; Electrodes; Electronics; Engineering; Environment; Evaluation; Filament; Healed; Implant; In Vitro; Inflammatory; Laboratories; Life; Medical Device; Metals; Methods; Michigan; Microglia; Neurons; Performance; Peripheral Nerves; Polymers; Reaction; Research; Retinal; Role; Slice; Surface; Technology; Technology Transfer; Therapeutic; Time; Tissues; Universities; Work; Wound Healing; abstracting; deep brain stimulator; design; healing; implantable device; improved; in vivo; interest; monomer; nanoscale; neurotrophic factor; novel; polymerization; relating to nervous system; response

DESCRIPTION (provided by applicant): Project Summary / Abstract - Perhaps the most important problem limiting the performance and utility of electronic biomedical devices that are implanted in tissue is the reactive response near the electrode that limits performance over extended periods of time. In the cortex, this is known to involve the activation of microglia and astrocytes, and the associated die-off of target cells (neurons) in a region of ~100 microns proximal to the probe surface. Strategies to overcome this problem have included the use of anti-inflammatory agents and neurotrophic factors. However, it is not clear that inflammatory agents will work over the long term. Attracting the neurons to the electrode is also a strategy that may not work well, since the inorganic electrode surface represents an interface between the hard metallic or semiconducting engineered device and the much softer organic tissue, and is thus inevitably a mechanically unstable environment that is dangerous for cell viability. It would therefore be useful if there were some alternative means to create nanoscale, electronically active filaments that were an extension of the metal electrodes, providing an efficient means of communication across the reactive scar and out into the surrounding tissue. Here we propose a method that may accomplish this by the direct, in- vivo polymerization of conducting polymers such as poly(3,4-ethylenedioxythiophene) (PEDOT). PEDOT is a conjugated polymer that is effective at facilitating charge transport between metallic electrodes and ionically conductive tissue. In previous work in our laboratory, we have shown that PEDOT coatings can help to improve the performance of biomedical devices such as microfabricated cortical probes in vivo. We have also demonstrated that PEDOT can be electrochemically polymerized around living cells both in-vitro and in-vivo. In slice cultures, we have shown that PEDOT can be grown out and into cortical tissue for 1000 microns or more, much larger than the ~100 micron size typical of the reactive cell layer. However many questions remain about the detailed methods of polymerization, including monomer delivery rates, influence of healing, and the viability and remodeling of cells in the polymerization zone. In this project we will investigate the in-vivo polymerization of PEDOT into living tissue, and will evaluate its impact on the performance of the biomedical devices of interest. We will investigate the role of wound healing around the probe on the subsequent polymerization and associated cell physiology in the reactive zone by waiting for different periods of time before initiating the reaction. We will focus our attention on microfabricated cortical electrodes of interest to the Center for Neural Communications Technology at the University of Michigan, directed by Daryl Kipke. This method has the potential to revolutionize the performance of a wide variety of implantable electronic biomedical devices including cortical probes, retinal implants, deep brain stimulators, and cardiac pacemakers. If this novel research eventually proves to be successful, there is considerable potential to move these methods from the laboratory to further development. Certain aspects of this work are related to inventions disclosed to the University of Michigan Technology Transfer Office, and under commercial development by Biotectix LLC, a spin-off company. Prof. Martin is a Co- Founder and Chief Scientific Officer for Biotectix LLC (www.biotectix.com).

描述(由申请人提供)： 项目摘要/摘要-也许限制植入组织中的电子生物医学设备的性能和实用性的最重要问题是电极附近的反应，这种反应会在较长时间内限制性能。在大脑皮层，已知这涉及小胶质细胞和星形胶质细胞的激活，以及探针表面近100微米范围内靶细胞(神经元)的相关死亡。克服这一问题的策略包括使用抗炎药和神经营养因子。然而，目前还不清楚发炎因素是否会长期发挥作用。将神经元吸引到电极上也是一种可能不太奏效的策略，因为无机电极表面代表着硬金属或半导体工程设备与软得多的有机组织之间的界面，因此不可避免地是一个机械不稳定的环境，对细胞生存是危险的。因此，如果有一些替代方法来创造纳米级的电子活性细丝，这些细丝是金属电极的延伸，提供一种跨越反应性疤痕并向外进入周围组织的有效通信手段，这将是有用的。在这里，我们提出了一种方法，可以通过导电聚合物的直接体内聚合来实现这一点，例如聚(3，4-乙二氧基噻吩基)(PEDOT)。PEDOT是一种共轭聚合物，有效地促进了金属电极和离子导电组织之间的电荷传输。在我们实验室以前的工作中，我们已经证明PEDOT涂层可以帮助提高生物医学设备的性能，例如体内微制造的皮质探针。我们还证明了PEDOT在体外和体内都可以在活细胞周围进行电化学聚合。在切片培养中，我们已经证明PEDOT可以长出并进入皮质组织1000微米或更多，远远大于反应细胞层的典型尺寸~100微米。然而，关于聚合的具体方法仍然存在许多问题，包括单体递送速度、愈合的影响以及聚合区细胞的活性和重塑。在这个项目中，我们将研究PEDOT在活体组织中的聚合，并将评估其对感兴趣的生物医学设备性能的影响。我们将通过在启动反应之前等待不同的时间段来研究探针周围的伤口愈合对后续聚合和反应区相关细胞生理的作用。我们将把注意力集中在密歇根大学神经通信技术中心感兴趣的微制皮质电极上，由达里尔·基普克指导。这种方法有可能彻底改变各种植入式电子生物医学设备的性能，包括皮质探头、视网膜植入物、脑深部刺激器和心脏起搏器。如果这项新颖的研究最终被证明是成功的，那么将这些方法从实验室转移到进一步开发的潜力是相当大的。这项工作的某些方面与向密歇根大学技术转移办公室披露的发明有关，并由剥离出来的公司Biotectix LLC进行商业开发。马丁教授是Biotectix LLC(www.Biotectix.com)的联合创始人兼首席科学官。