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Improving the Biocompatibility of Neural Recording Arrays with ECM Coatings

$186,250R21FY2015NSNIH

University Of Utah, Salt Lake City UT

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Abstract

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.

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