LOGOS-TBI: Light-controlled Organic Semiconductor Implants for Regeneration after TBI

Background: Traumatic brain injury (TBI) is a leading cause of death and disability among young adults. The impairment of the often very young patients in daily life is a heavy burden for the affected person and leads to high healthcare costs. In recent years, electrostimulation of neurons has been suggested a promising approach to induce functional recovery of injured neuronal connections. However, standard electrode stimulation techniques require invasive methods and wiring of the patient. Purpose: We aim to combat TBI-induced disabilities by re-establishing neuronal connectivity. We will use light-sensitive semiconductors (photocaps) made from industrial colorants. They are easily available, stable, and non-toxic. Photocaps enable electrical stimulation of neurons with safe light intensities without the need for external wiring. Hypothesis: We suppose that the stimulation of neuronal cells via light-activated photocaps fosters functional recovery after TBI. Approach: In a multidisciplinary research approach we investigate the photocaps performance and effects on living systems. Cultured cells are an invaluable tool to develop optimal stimulation parameters before progressing to healthy and injured brain tissue. We will investigate the optimal time window after TBI in which stimulation yields the most extensive regenerative results. Our interdisciplinary research program brings together young independent researchers with backgrounds from neuroscience (Dr. Muammer Ücal), structural biology (Dr. Karin Kornmüller), electrophysiology (Dr. Susanne Scherübel) and electrical engineering (Dr. Theresa Rienmüller). Experiments will be conducted at the Medical University of Graz and Graz University of Technology.

Neurostimulation stands as a pivotal technique in both research and clinical applications. The development of wireless neurostimulation methods represents a significant goal in this field, with researchers aiming to minimize invasiveness and enhance patient comfort by eliminating the extensive cabling for treatment of nervous system problems such as motor disability, epilepsy, and enhancing rehabilitation post-stroke or injury. Organic electrolytic photocapacitors (OEPC) are particularly promising for achievement of simple and wireless device design. They convert light pulses into electric fields within thin layers, thereby significantly reducing the size of the stimulatory devices, whilst ensuring stimulation of excitable cells. The primary objective of this project was to investigate the feasibility, biocompatibility, and efficacy of wireless light-controlled OEPC in neurostimulation and in enhancing endogenous regenerative responses. Using various models encompassing cell and tissue cultures, computational and animal models we showed that these devices are safe and biocompatible for semi-chronic applications. Light stimulation of brain cells on OEPC led to elevated nerve cell activity. This effect was achieved primarily through the device's photoactive layer, with signal propagation observed within the neuronal network. OEPC stimulation of brain tissue cultures similarly yielded increased nerve cell activity. Daily stimulation sessions over seven days led to the expression of regenerative proteins in tissue cultures, suggesting potential beneficial effects of the treatment. In an animal model, flexible OEPC were implanted on top of the rat brains. Three weeks after implantation, OEPC stimulation resulted in increased nerve activity not only in the superficial areas but also in the deeper brain regions, across both brain hemispheres, indicative of signal propagation across the brain network. Implanted devices evoked no foreign body reactions and remained functional during implantation period. Electron microscopy revealed a smoother surface of the implanted device, suggesting a mild wear-out of the devices, which did not negatively influence device functionality. The successful application of OEPC could bring significant benefits to the field of brain stimulation, offering a wireless, lightweight alternative to conventional methods. The devices demonstrated both safety and functionality for applications over semi-chronic periods, and indicators of regenerative responses in the nervous tissue underscoring their potential as therapeutic implants or platforms for further scientific studies. Full assessment of their safety and efficacy, however, require prolonged investigations in preclinical applications.