Glial cell responses on tetrapod-shaped graphene oxide and reduced graphene oxide 3D scaffolds in brain in vitro and ex vivo models of indirect contact.

Brain implants are promising instruments for a broad variety of nervous tissue diseases with a wide range of applications, e.g. for stimulation, signal recording or local drug delivery. Recently, graphene-based scaffold materials have emerged as attractive candidates as neural interfaces, 3D scaffolds, or drug delivery systems due to their excellent properties like flexibility, high surface area, conductivity, and lightweight. To date, however, there is a lack of appropriate studies of the foreign body response, especially by glial cells, towards graphene-based materials. In this work, we investigated the effects of macroscopic, highly porous (>99.9%) graphene oxide (GO) and reduced graphene oxide (rGO) (conductivity ∼1 S m ^-1 ) scaffolds with tailorable macro- and microstructure on human astrocyte and microglial cell viability and proliferation as well as expression of neuroinflammation and astrogliosis associated genes in an indirect contact approach. In this in vitro model, as well as ex vivo in organotypic murine brain slices, we could demonstrate that both GO and rGO based 3D scaffolds exert slight effects on the glial cell populations which are the key players of glial scar formation. These effects were in most cases completely abolished by curcumin, a known anti-inflammatory and anti-fibrotic drug that could in perspective be applied to brain implants as a protectant.