Dissertation/Thesis Abstract

Biologically-informed investigations to reduce the foreign body response to central nervous system implants
by Oakes, Robert Smith, Ph.D., The University of Utah, 2016, 132; 10120771
Abstract (Summary)

Neural recording devices are a therapeutic and diagnostic option for central nervous system (CNS) diseases and a vital component of neuroscience research. However, poor functional longevity is a major hurdle facing this broad class of devices. Decreases in functionality are associated, in part, with the foreign body response (FBR) surrounding chronically implanted recording devices; which includes chronic inflammation, astrogliosis, blood-brain barrier (BBB) leakiness, and neuronal cell death. Two potential areas for intervention were explored including the initial hemorrhage that results from device insertion and the neuroinflammatory sequela. Researchers have shown that cellular interactions with extracellular matrix (ECM) are able to affect both of these aspects of the FBR. The central hypothesis driving this work is that ECM coatings which target the initial hemorrhage, should decrease the FBR. This was investigated by coating silicon microelectrode arrays (MEAs) with ECM and implanting them into motor cortex of rats. Two ECM coatings were investigated, including the xenogeneic clinically-used Avitene Microfibrillar Collagen Hemostat and allogeneic astrocyte-derived ECM. Results show that the allogeneic astrocyte-derived ECM decreased astrogliosis within the recording zone at the 8-week time point. This decrease in astrogliosis may improve device functionality, as indicated by previous studies that correlated recording metrics to histology. Interestingly, the xenogeneic Avitene coating increased IgG within the recording zone at the 8-week time point. Collectively, these results show that ECM coatings with different genetic backgrounds and compositions are able to differentially affect specific aspects of the FBR. To broaden the knowledge on the FBR to neural recording devices, the FBR of headstage components used to anchor CNS devices to the skull was analyzed. Results showed that the FBR to fixation screws and fixation anchoring adhesive illicit a chronic FBR that has all of the hallmarks described for MEAs implanted in brain tissue. Moreover, results show evidence of persistent neuroinflammation below a variety of fixation screws including chronic macrophage activation, demyelination, and neural tissue loss. Understanding the FBR of fixation techniques, which is common to a wide variety of CNS devices, may improve the biocompatibility of existing devices and provide a reference for future biologically-informed device designs.

Indexing (document details)
Advisor: Tresco, Patrick A.
Commitee: Dorval, Alan Dale, Grainger, David W., Hlady, Vladimir, House, Paul A.
School: The University of Utah
Department: Bioengineering
School Location: United States -- Utah
Source: DAI-B 77/10(E), Dissertation Abstracts International
Source Type: DISSERTATION
Subjects: Neurosciences, Biomedical engineering, Materials science
Keywords: Astrogliosis, Extracellular matrix, Foreign body response, Inflammation, Macrophage, Neural prosthesis
Publication Number: 10120771
ISBN: 9781339819495
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