GRK 2154 - Materials for Brain

P7: Rescue me! Approaches to overcome the brain foreign body response towards implant materials (K. Hattermann-Koch)

The implantation of foreign materials into the brain is frequently accompanied by the formation of a glial scar, a fibrous sheath from glial derived cells and extracellular matrix around the implanted structure, for example a stimulation electrode. In case of drug delivery implants, this glial scar may influence the availability and effects of the drug, e.g. by reduction of the diffusion, changes in the extracellular matrix composition and the degradation of biodegradable barrier layers and implant materials. Thus, the drug release may be significantly impeded. The formation of the glial scar occurs upon a first, acute inflammation process caused by the initial wound in the brain parenchyma, and a second, chronic phase. Accordingly, we want to use a two-step in vitro approach to minimize glial scar formation in order to improve biocompatibility of brain implants: First, we want to investigate if neuroprotective drugs, which are currently under investigation for the rescue of neurons in the penumbra region after stroke, may also milden the acute reaction towards the implantation. In this project part, we will analyze the effects of the drugs in human cell lines and murine acute brain slices, in combination with materials developed by the first PhD student cohort as well as newly developed materials from the current cohort. The second approach is closely linked to material science projects focusing on (hydrogel) coatings for implants. Assuming that glial scar formation may be a valuable rescue mechanism in brain injury by separating the affected brain area and preparing the injured region for regeneration, we postulate that chronic foreign body reactions might be eased by surface coatings that mimic the glial scar softness/stiffness and extracellular matrix composition. Thus, we want to identify biologically relevant molecules (signal mediators, ECM components etc.), together with the coating projects which bring in the appropriate coatings, and analyze the effects on the chronic foreign body reaction.