An ex vivo method for evaluating the biocompatibility of neural electrodes in rat brain slice cultures

Failure of neural recording electrodes implanted in the brain is often attributed to the formation of glial scars around the implant. A leading cause of scar formation is the electrode material. Described below is an approach to evaluate the biocompatibility of novel electrode materials in a representative three-dimensional model. The model, brain slice culture, accounts for the response of the neural tissue in the absence of the systemic response. While limitations of any in vitro model exist, brain slice culture provides an indication of the response of neurons and glia in an environment more indicative of the in vivo environment than two-dimensional cell culture of glia or neurons alone. Polybenzylcyclobutene (BCB) electrodes were developed as test materials for flexible electrodes due to ease of processing, low water uptake, and inherent flexibility when formed in thin sheets. Biocompatibilty of the BCB neural electrodes was evaluated using living brain slices derived from the hippocampal regions of 100 g CD rats. Importantly, fewer animals can be used in brain slice culture to evaluate the neural tissue response than when using live animals, since several slices can be obtained per animal. Cellular response to the electrodes was evaluated at 0, 7, and 14 days. At all time points living cells, both neurons and glia, were observed in the vicinity of the electrode. In addition, cells were observed migrating out from the brain slices onto the shank of the BCB electrode. Brain slice culture is shown to be a viable alternative to in vivo evaluation, in that the response of both neurons and glia can be evaluated in a native three-dimensional state, while sacrificing fewer animals. Future in vivo evaluation with BCB will provide definitive answers on the degree of glial scarring in response to this new and biocompatible electrode material.