Glial cells play an important role in Alzheimer’s disease (AD) and chronic neuropathic pain, affecting more than 500 million people worldwide. In the US alone, this leads to annual costs of $600 billion for treatment and lost productivity. Conventional pharmacological treatments are only partially effective and are associated with significant side effects. There is an urgent need for the development of a safe, non-addictive, non-opioid-based therapy that also possesses disease-modifying properties. Recently, there has been growing excitement around treating neurological diseases using neuromodulation techniques. Flickering strobe lights at gamma-frequency of 40 Hz have shown very promising results in mouse models where microglia immune cells could be activated and contributed to degradation of amyloid- proteins. The current modulation devices, however, are comparable to that of early cardiac pacemakers, leading to fibrotic encapsulation within weeks. This is mainly predicated on the neural probe’s mechanical properties, given by the hard electrodes from the semiconductor industry. Our proposed approach for ten thousand times softer electrodes is based on nano engineered neural interfaces (NENI) - hybrid microstructured polymer pads covered by ultra-thin and soft nanostructured metal/elastomer compounds.
Was ist das Besondere an diesem Projekt?
Life expectancy has increased dramatically in industrialized countries, making us more vulnerable to many age-related diseases. Our vision is to bring science to daily life by developing biomimetic platforms for interfacing with neural tissue to help people suffering from neurodegenerative diseases. The basic research on soft and nanostructured electrodes was conducted from 2013 to 2017 within the nano-tera.ch project on dielectric elastomer transducers funded by the Swiss National Science Foundation. In 2018, the technology transfer office of the University of Basel - Unitectra funded a follow-up project to fabricate a proof-of-concept prototype based on ultra-thin polymer films. Within the current Gebert Rüf Pilot Project, we are validating different stimulation protocols of non-neuronal cells using an in-vitro approach with NENI electrodes. Once successful, electrical stimulation protocols derived from in-vitro experiments will be translated to non-invasive transcranial electrical stimulations. By this, AD patients will benefit much earlier from our results and since the approach is non-invasive, it will become more accessible to a broader range of patients.
The activities within this GRS pilot project are essential to translate the scientific results towards the clinical translation phase. So far, the following milestones have been achieved:
• Electrical stimulation of BV2 cells using NENI paddles and 3D printed cell chambers.
• Laser-induced micro-perforations of PEEK films to increase flexibility/adaption to 3D topology.
• Hot-embossing of amorphous 75 µm PEEK films: Application of microstructures while keeping the PEEK film transparent and non-crystalline.
• 3rd generation of NENI electrodes with tuned topology, mechanical properties and surface chemistry.
• High-power impulse magnetron sputtering (HiPIMS) of Au-films on adhesive Ti-films without breaking the ultra-high vacuum resulting in better electrical conductivity.
• Integration of electronics/application-specific integrated circuit on the NENI paddle (work in progress).
• Cyclic loading tests of NENI implants (work in progress).
B. Osmani, H. Schift, K. Vogelsang, R. Guzman, M. Kristiansen, R. Crockett, A. Chacko, S. Bucher, T. Töpper, B. Müller, "Hierarchically structured polydimethylsiloxane films for ultra-soft neural interfaces," Micro and Nano Engineering 7, 100021 (2020).
B. Osmani, T. Töpper, B. Müller, "Conducting and stretchable nanometer-thin gold/thiol-functionalized polydimethylsiloxane films," Journal of Nanophotonics 12(3), 033006 (2018).
B. Osmani, H. Deyhle, T. Töpper, T. Pfohl, B. Müller, “Gold layers on elastomers near the critical stress regime,” Advanced Materials Technologies 2, 1700105 (2017).
B. Osmani, G. Gerganova, B. Müller, “Biomimetic nanostructures for the silicone-biosystem interface: tuning oxygen-plasma treatments of polydimethylsiloxane,” European Journal of Nanomedicine 9(2), 69-77 (2017).
Am Projekt beteiligte Personen
Dr. Bekim Osmani
, Project leader, Department of Biomedical Engineering, University of Basel
Prof. Dr. med. Raphael Guzman, Department of Neurosurgery, University Hospital Basel
Alois C. Hopf, MSc ETH Zürich, PhD candidate at the Department of Biomedicine, University of Basel:
Dr. Helmut Schift, Laboratory for Micro- and Nanotechnology, Paul Scherrer Institute
Prof. Dr. Per Magnus Kristiansen, Institute of Polymer Nanotechnology (INKA), FHNW Windisch
Prof. Dr. Hans J. Hug, Magnetic and Functional Thin Films, Empa Dübendorf
Prof. Dr. Bert Müller, Biomaterials Science Center, Department of Biomedical Engineering, University of Basel
Dr. Tino Töpper, Biomaterials Science Center, Department of Biomedical Engineering, University of Basel
Letzte Aktualisierung dieser Projektdarstellung 18.11.2020