Peptide Modification of Polyimide-Insulated Microwires for Reducing Glial Scarring

• Author / Creator

  Sridar,Sangita

• 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.

• Subjects / Keywords

  • Peptide modification, Glial scarring

• Graduation date

  Fall 2015

• Type of Item

  Thesis

• Degree

  Master of Science

• DOI

  https://doi.org/10.7939/R3V11VR4G

• License

  This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for non-commercial purposes. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.