Poloxamer (PLX) coatings modulate chronic inflammation and enhance biocompatibility of multichannel microelectrode arrays

Abstract

Traumatic brain injury is responsible for the loss of neural function in millions of patients across the United States every year. Neural electrodes show potential in significantly enhancing the quality of life of these patients by restoring lost communication with the body. For example, a microelectrode sensor designed for human quadriplegic patients allows them to move a cursor on the screen using single neuron activity. Long term electrode implantation in the brain, however, leads to glial scar formation, thereby limiting the functional lifetime of an electrode in vivo. In this thesis, we investigated the biocompatibility of ceramic based multichannel electrodes coated with Poloxamer – 188 (PLX), a bifunctionalized co-polymer that may self insert into damaged neuronal membranes and limit cellular damage. In order to do this, we first developed a method to quantify inflammatory cells around the microelectrode. Then, using immunohistochemical staining techniques, presence and expression of microglia/macrophages (ED1), astrocytes (GFAP), and intact neurons (NeuN) were observed at 2, 4, and 6 week intervals post implantation. Cells were characterized in terms of proliferation (stereological analysis) and morphology (intensity of fluorescent staining). Our results showed that PLX coated electrodes significantly reduced the presence of microglia and macrophages at 2 weeks, 4 weeks, and at 6 weeks post implantation as evident by relative fluorescence of ED1 staining. Similarly, GFAP staining shows decreased protein expression of astrocytes at 2 week and 4 week time points. In contrast, NeuN staining revealed that PLX is associated with increased neuronal presence in the vicinity of the implant site at 2 week and 4 week time points but not at the 6 week time point. The demonstrated modulation of the immune response seen in electrodes coated with PLX coatings show promise in its future application as a mode of protecting and extending the functional lifetime of implanted neural electrodes. In the long term, we hope that implementation of a poloxamer coated microelectrode surface will lead to chronically implantable microelectrode devices capable of recording neurons for longer periods. This will enable the use of microelectrode dependent neuroprosthetics as viable alternatives to patients who have lost motor functions due to brain injury.M.S., Biomedical Engineering -- Drexel University, 201

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