Effects of dip-coated films on the properties of implantable intracortical microelectrodes
The successful clinical use of implantable intracortical microelectrodes (ICMs) to treat certain types of deafness, blindness, and paralysis is limited by a reactive tissue response (RTR) of the brain. This RTR culminates in the formation of a tight glial scar and a loss of neuronal density around implanted ICMs, and is accompanied by a decrease in signal to noise ratio and an increase in impedance. While no comprehensive mechanistic understanding of the underlying biology is currently agreed upon in the field, a general consensus exists around a highly volatile acute RTR phase. During this acute phase, the electrical properties of ICMs do not always coincide with cellular responses, and the extent of initial injury appears to greatly influence the degree of the chronic RTR. While many electrode modifications and treatments are effective in the short term, the chronic RTR appears impervious to most interventions. To better understand the acute phase of the RTR, this dissertation aims to investigate the effects of various dip-coated biomolecules on the electrical properties of ICMs and cellular responses to microscale ICM-like foreign bodies. We first present an examination of silica sol-gel thin films as a potential biomolecule delivery platform which does not adversely affect the electrical properties of ICMs. The second study shows that adsorbed proteins, thought to play an important role in modulating the RTR, cause significant increases in electrode impedance. In contrast to prevalent electrical models of the electrode tissue interface which assume purely resistive impedance changes due to adsorbed proteins, our results show both resistive and capacitive changes. We also show that increases in impedance related to protein adsorption can be prevented by dip coating ICMs in an aqueous solution of high molecular weight polyethylene glycol (PEG). We then describe a method to clean electrode sites using direct current (DC) biasing, showing that DC biasing is capable of restoring electrode impedance following exposure to enzymatic cleaning solutions, proteins, phantom brains, and actual brain tissue. The final study in an in vitro mixed primary cortical cell culture model shows that lipopolysaccharide (LPS), a well-known ligand to toll-like 4 (TL4) receptors, dip-coated onto segments of metal microwire, can simulate localized inflammation around an implanted ICM. We observe elevated activation of glial cells in interface regions, and extending into more distant regions. This elevation in glial responses is not accompanied by a decrease in neuronal density. We additionally show that microwire dip-coated with a mixture of LPS and PEG exhibits significantly lower microglial and astrocyte responses. These findings highlight the importance of adsorbed proteins, some of which are implicated in aggravating the reactive tissue response, but which we show can result in significant increases in electrode impedance before the RTR even begins. These impedance changes can be prevented through the use of dip-coated PEG. Our cell culture data presents further evidence for the attractiveness of TL4 receptors as a target for intervention, and suggests that the loss of neuronal density observed in vivo is better explained by other mechanisms following device insertion than pure glial activation.
Rickus, Purdue University.
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