Improving the Biocompatibility of Neural Recording Arrays with ECM Coatings

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脑机接口（BCI）的治疗潜力，但这种有前途的技术的使用受到性能不一致和最终记录失败的限制。 虽然确切的机制尚不清楚，但大脑对植入物的异物反应（FBR）被认为是问题的根源。 FBR的主要特征是慢性炎症，这是在许多CNS疾病中也观察到的性质，其中巨噬细胞活化和血脑屏障（BBB）的破坏是一种自我维持的循环，已观察到复发和缓解，并且可能在记录不稳定性中起关键作用。 了解如何降低FBR将导致 改善记录微电极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。 我们假设，细胞适当的ECM涂层可以限制与电极植入相关的失血，并随后减少留置期间的神经炎症，导致FBR降低，这将改善记录的一致性和寿命。 虽然一段时间以来已知细胞外基质蛋白质胶原具有止血性质，但ECM的免疫调节性质仅在最近才被描述。 为了验证这一假设，我们将使用一种新的方法从星形胶质细胞、神经胶质祖细胞和间充质基质细胞（MSC）中收获ECM，并筛选它们在体外凝血、血小板聚集和减少巨噬细胞活化方面的有效性。 然后，我们将研究这种涂层是否减少失血，降低FBR，并提高神经记录性能植入皮质脑组织使用大鼠模型。 该项目的主要目标是推进植入式神经记录阵列技术作为一种基础科学工具，并增加临床应用。

DESCRIPTION (provided by applicant): Despite substantial progress in implantable recording technology and several proof-of principle experiments demonstrating therapeutic potential as a Brain Computer Interface (BCI), the use of this promising technology is limited by inconsistent performance and eventual recording failure. Although the precise mechanisms are unknown, the foreign body response (FBR) that the brain mounts against the implant is believed to underlie the problems. A major feature of the FBR is chronic inflammation, a property that is also observed in many CNS disorders, 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 recording instability. Understanding how to reduce the FBR will lead to strategies that improve the biocompatibility of recording microelectrodes and extend their usefulness as a basic science tool and in clinical applications. We hypothesize that cell appropriate ECM coatings can limit blood loss associated with electrode implantation and subsequently reduce neuroinflammation during the indwelling period resulting in a reduction of the FBR that will improve recording consistency and longevity. While it has been known for some time that the extracellular matrix protein, collagen, possesses hemostatic properties, the immunomodulatory properties of ECM has only recently been described. To test the hypothesis, we will use a novel approach to harvest ECM from astrocytes, glial progenitors and mesenchymal stromal cells (MSCs) and screen their effectiveness at blood clotting, platelet aggregation and reducing macrophage activation in vitro. We will then investigate whether such coatings reduce blood loss, lower the FBR, and improve neural recording performance following implantation cortical brain tissue using a rat model. The broad objective of this project is to advance implantable neural recording array technology as a basic science tool and toward increased clinical use.