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Peptide Modification of Polyimide-Insulated Microwires for Reducing Glial Scarring Open Access


Other title
Peptide modification, Glial scarring
Type of item
Degree grantor
University of Alberta
Author or creator
Supervisor and department
Elias,Anastasia (Chemical and Materials Engineering)
Examining committee member and department
Todd,Kathryn (Psychiatry), Unsworth, Larry (Chemical and Materials Engineering)
Department of Chemical and Materials Engineering
Materials Engineering
Date accepted
Graduation date
Master of Science
Degree level
Neuroprosthetic devices are either stimulation or recording electrodes that are used to restore functionality of the human body after neural injury or disease. The long-term utility of these devices is limited by their viability and stability within the central nervous system due to foreign body response from glial cells, namely microglia and astrocytes. During this response, these glial cells form scar tissue (glial scar) around the implant (to isolate the device and electrically insulate from the neurons). These cells also secrete chemicals to inhibit the outgrowth of neuron processes, which affects the electrode function. This work focuses on a method for modulating the responses from the microglia and astrocyte to reduce scarring around microstimulation electrodes comprised of polyimide-insulated platinum (Pt) / iridium (Ir) metal alloy. The surface of the electrodes are functionalized with a specific peptide – with the sequence KHIFSDDSSE – to modulate the glial scar. This peptide is similar to the homophilic binding site of neural cell adhesion molecules (NCAM). In this work, it was shown that this peptide reduced the proliferation of microglia and astrocytes (when added in solution to pure astrocyte cultures). The responses of microglia and astrocytes to both peptide-coated and uncoated electrodes were tested in 3D gels. From these tests, fewer microglia were found in the region surrounding peptide-coated electrodes than uncoated electrodes. The modulation of microglial response is indicative of modulation of the acute response. Astrocytes preferentially attached to the peptide-coated electrode, and the number of attached astrocytes remained the same up to 2 weeks post implantation compared to the uncoated electrode. The modulation of astrocyte response is indicative of modulation of the initial stages of the chronic response. These results suggest that this peptide could be used to modulate scar tissue formation by glial cells.
Permission is hereby granted to the University of Alberta Libraries to reproduce single copies of this thesis and to lend or sell such copies for private, scholarly or scientific research purposes only. The author reserves all other publication and other rights in association with the copyright in the thesis and, except as herein before provided, neither the thesis nor any substantial portion thereof may be printed or otherwise reproduced in any material form whatsoever without the author's prior written permission.
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