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，并且有几个原理验证实验证明了作为脑机接口（BCI）的治疗潜力，但由于性能不一致和最终记录失败，这项有前途的技术的使用受到限制。虽然确切的机制尚不清楚，但大脑对植入物产生的异物反应（FBR）被认为是问题的根源。FBR的一个主要特征是慢性炎症，在许多中枢神经系统疾病中也观察到这一特性，其中巨噬细胞激活和血脑屏障（BBB）的破坏是一个自我维持的循环，已被观察到复发和消退，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

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.