Electrodes of the conjugated polymer poly(3,4-ethylene dioxythiophene) (PEDOT) have been shown to possess very attractive electrochemical properties for functional electrical stimulation (FES) or recording in the nervous system. Biomolecules already present in nervous tissue, added as counter ions in PEDOT electropolymerisation, could be a route to further improve the biomaterial properties of PEDOT, eliminating the need of surfactant counter ions like docedyl benzene sulphonate (DBS) or polystyrene sulphonate (PSS) in the polymerisation process. Such PEDOT/biomolecular composites using heparin, or hyaluronic acid, have been electrochemically investigated in a previous study and have been shown to retain the attractive electrochemical properties already proven for PEDOT:PSS.
The aim of the present study is to evaluate biocompatibility of these PEDOT/biomolecular composites in vitro and also evaluate PEDOT:heparin biocompatibility in cortical tissue in vivo. Hereby, we also aim to identify a suitable test protocol, that can be used in future evaluations when further material developments are made.
Material toxicity was first tested on cell lines, both through a standardised agarose overlay assay on L929 fibroblasts, and through elution tests on human neuroblastoma SH-SY5Y cells. Subsequently, a biocompatibility in vivo test was performed using PEDOT:heparin coated platinum probes implanted in the cerebral cortex of Sprague-Dawley rats. Tissue was collected at three weeks and six weeks of implantation and evaluated by immunohistochemistry.
No cytotoxic response was seen to any of the PEDOT:biomolecular composites tested here. Furthermore, elution tests were found to be a practical and effective way of screening materials for toxicity and had a clear advantage over the agarose overlay assay, which was difficult to apply on other cell types than fibroblasts. Elution tests would therefore be recommendable as a screening method, at all stages of material development. In the in vivo tests, the stiffness of the platinum substrate was a significant problem, and extensive glial scarring was seen in most cases irrespective of implant material. However, quantification of immunological response through distance measurements from implant site to closest neuron, and counting of macrophage densities in proximity to polymer surface, was comparable to those of platinum controls. These results indicate that PEDOT:heparin surfaces were as compatible with cortical tissue as pure platinum controls.