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.

Public Health Relevance

Implantable neural recording arrays have shaped our understanding of how the brain works, and, more recently, have been used experimentally to treat such disorders as paralysis that provide hope for many suffering from this disability. However, the technology has been challenging to implement reliably and over long time periods, which limits its use. Our project is focused on improving recording device biocompatibility and long-term function through the development of an innovative approach that uses cell-derived extracellular matrix coatings to limit blood loss associated with electrode implantation and subsequently reduces the neuroinflammatory sequela associated with the FBR. While this project focuses on improving the biocompatibility of implantable recording technology for use in science and medicine, the approach it is widely applicable to other chronic indwelling devices where minimizing the FBR is essential to promote better long-term function and improve the health of patients with such devices.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Exploratory/Developmental Grants (R21)
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Special Emphasis Panel (BNVT)
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Ludwig, Kip A
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University of Utah
Biomedical Engineering
Schools of Engineering
Salt Lake City
United States
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Oakes, Robert S; Polei, Michael D; Skousen, John L et al. (2018) An astrocyte derived extracellular matrix coating reduces astrogliosis surrounding chronically implanted microelectrode arrays in rat cortex. Biomaterials 154:1-11
Hsiao, Tony W; Tresco, Patrick A; Hlady, Vladimir (2017) Astrocyte spreading and migration on aggrecan-laminin dot gradients. Biointerphases 13:01A401
Hsiao, Tony W; Tresco, Patrick A; Hlady, Vladimir (2015) Astrocytes alignment and reactivity on collagen hydrogels patterned with ECM proteins. Biomaterials 39:124-30