Improving the Biocompatibility of CNS Devices

提高中枢神经系统设备的生物相容性

• 批准号: 9241454
• 负责人: Patrick A Tresco
• 金额: $ 33.1万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-03-15 至 2021-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9241454
• 关键词: Address; Allogenic; Area; Astrocytes; Base Sequence; Basic Science; Biological; Blood - brain barrier anatomy; Blood Vessels; Brain; Brain Injuries; Cells; Chronic; Clinic; Clinical; Clustered Regularly Interspaced Short Palindromic Repeats; Demyelinations; Development; Device Designs; Devices; Disease; Electrodes; Elements; Extracellular Matrix; FDA approved; Failure; Foreign Bodies; Future; Genes; Genome engineering; Goals; Gold; Hemorrhage; Hemostatic Agents; Hydrogels; Implant; Inflammation; Inflammatory; Knowledge; Link; Longevity; Macrophage Activation; Mesenchymal Stem Cells; Methods; Microelectrodes; Modeling; Modification; Neurosurgical Procedures; Paralysed; Performance; Phenotype; Play; Property; Rattus; Regulation; Relapse; Source; Surface; System; Technology; Testing; Therapeutic; Time; Tissues; Utah; Work; astrogliosis; base; biomaterial compatibility; brain circuitry; brain tissue; clinical application; clinical translation; comparative efficacy; cytokine; density; design; disability; experimental study; genetic approach; healing; immunoregulation; implantable device; implantation; improved; insight; macrophage; neural circuit; neuroinflammation; neuron loss; next generation; progenitor; prototype; public health relevance; receptor expression; relating to nervous system; response; tool

 DESCRIPTION (provided by applicant): Despite substantial advances in implantable recording technology and several proof-of principle experiments demonstrating its therapeutic potential, the use of this promising technology is limited by inconsistent performance and eventual failure over chronic time frames. To date, the design strategy employed to advance the technology has been largely an empirical `build-and-test' approach with no overarching biologically- informed rationale. While it is widely believed that elements of the foreign body response (FBR) contribute to inconsistent single unit recording performance and failure, current devices in use were designed before much was known about the FBR. The major features uncovered thus far are related to the tissue damage that accompanies high-density recording array implantation and persistent inflammation, a property shared with the FBR to other CNS implants, where macrophage activation and disruption of the blood brain barrier (BBB) is a self-sustaining cycle that has been observed to relapse and remit, and likely plays a key role in single unit recording instability and eventual failure. Understanding how to reduce the initial damage caused by implantation and reduce the impact of the FBR will lead to strategies that improve the biocompatibility of recording microelectrode arrays and extend their usefulness as a basic science tool and in clinical applications. To address this area, our specific aims are directed at: 1) understanding whether it is possible to improve the recording performance of a current FDA-approved technology using a hemostatic and immunomodulation coating strategy; 2) studying how changes in device design influence single unit recording consistency and longevity; and, 3) using CRISPR-based sequence-specific regulation of inflammatory genes to reduce the FBR. The objective of this project is to develop a biologically informed strategy that will advance implantable neural recording array technology as a chronic basic science tool and toward increased clinical usage. The broader goal is to understand how to improve the biocompatibility of all types of chronic indwelling CNS implants.

 描述（由申请人提供）：尽管植入式记录技术取得了实质性进展，并且几项原理验证实验证明了其治疗潜力，但这种有前途的技术的使用受到长期时间范围内性能不一致和最终失败的限制。 迄今为止，用于推进该技术的设计策略主要是一种经验性的“构建和测试”方法，没有总体的生物学依据。 虽然人们普遍认为异物反应（FBR）的因素会导致单个装置记录性能不一致和故障，但目前使用的器械是在对FBR了解很多之前设计的。 迄今为止发现的主要特征与伴随高密度记录阵列植入和持续性炎症的组织损伤有关，这是FBR与其他CNS植入物共有的特性，其中巨噬细胞活化和血脑屏障（BBB）的破坏是一个自我维持的循环，已观察到复发和缓解，并且可能在单个单元记录不稳定性和最终失败中起关键作用。 了解如何减少植入引起的初始损伤并减少FBR的影响将导致改善记录微电极阵列的生物相容性并扩展其作为基础科学工具和临床应用的有用性的策略。 为了解决这一问题，我们的具体目标是：1）了解是否有可能使用止血和免疫调节涂层策略来改善目前FDA批准的技术的记录性能; 2）研究设备设计的变化如何影响单个单元记录的一致性和寿命;以及3）使用基于CRISPR的序列特异性调节炎症基因来降低FBR。 该项目的目标是开发一种生物学信息策略，将推进植入式神经记录阵列技术作为一种慢性基础科学工具，并增加临床使用。 更广泛的目标是了解如何提高所有类型的慢性留置CNS植入物的生物相容性。