Nanowires and Neural interfaces. Biocompatibility in the brain

Sammanfattning: Chronic neural interfaces that are able to record or stimulate neurons in the CNS are valuable instruments in use today and they hold great promise for the future both within neuroscience research and in the clinic. However, a major obstacle is that they show a decline in performance over time. Many different approaches to improve the interface designs are gradually evaluated in hope of overcoming this obstacle. One approach is to enhance the biomaterials ability to integrate with the surrounding tissue by manipulating the surface structure. One way of doing this is to construct a nanostructured electrode surface. A nanostructured electrode surface, in this case nanowires, has the potential to improve the electrical properties of the neural interface a well as to improve the interface biocompatibility and tissue integration. However, before nanowires can be used as an electrode surface structure it is crucial to investigate the safety aspects of exposing the brain tissue to nanowires. Nanowires share morphological features with asbestos fibers and if some of the nanowires were to break off from the electrode surface a possible asbestosis-like pathology might develop. To address this issue we assessed the inflammatory tissue response and neuronal survival following injection of biostable nanowires of different lengths (paper I). Furthermore, we also evaluated the tissue response following injection of short degradable nanowires (paper II). We found that short biodegradable or biostable nanowires did not cause a significant tissue response or neuronal loss. However, we found that debris from degradable nanowires as well as intact biostable nanowires remained in the brain one year post injection. Suggesting that nanoparticle clearance from the brain is a very slow process.A neural interface with a nanostructured surface needs to be protected from damage during the implantation procedure. In paper III, we showed that embedding the nanowire substrate in a temporary protective and stiffening matrix, consisting of gelatin and glycerol, preserved the majority of the nanowires during implantation into agar.In paper IV, we showed that implanting multiple wire bundles in the brain does not result in an increased glial response to each individual implant. This implies that it is feasible to interface and interact with several brain structures in parallel without the confounding factor of an over all cumulatively increased glial response.In summary, this thesis has provided key knowledge about how to design and implant a nanowire structured neural interface. The development of a seamlessly integrating neural interface would have immense implications in neuroscience research as well as in clinical settings.