Fabrication and characterization of silk reinforced, micropatterned cellulose films for soft neural implants

Recently, digital therapy for neurodegenerative diseases such as Alzheimer’s disease using high-frequency electrical signals has attracted attention. For these treatments, the spatial proximity of the electrodes to the neural tissue must be guaranteed, requiring neural probes to be implanted into the human brain. However, creating a glial scar-free neural-probe interface for extended periods of time is a challenge. Chronic inflammation around the implant occurs due to mechanical mismatch between brain tissue and probe. Soft and flexible electrodes could therefore be the key for the next-generation probes. The long-term functionality of the implant requires stability of the electrodes and resistivity to crack formation. In this work, we propose brain-probe interfaces based on cellulose films, which soften in water and adopt to the curvature of tissue after implantation. The ratio of the bio-based polymer, plasticizer and solvent was optimized to create soft films via blade coating. We reinforced the films by silk networks and improved metal adhesion by means of micropatterning. Mechanical tests showed that the cellulose films had an elastic modulus of about 100 MPa. The silk embedding allowed for an improvement of the tear strength by a factor of seven, maintaining flexibility and softness. The stability of the nanometer-thin electrodes was evaluated by mechanical fatigue tests, peel-tests and conduction measurements under relevant strains. Flexible micropatterned Au electrodes in phosphate buffer saline demonstrated stable behavior over 10,000 loading cycles. No crack formation via water-uptake was observed. Moreover, compared to flat electrodes, the two-directional micropatterned ones could withstand up to 30 % strain and behaved as a framework. The adhesion of Au electrodes to the cellulose film was substantially improved by the proper choice of height-to-width ratio of the microstructures. We hypothesize that the adhesion could be improved as the result of the rather low glass transition temperature. This temperature might be reached at the surface of micropatterned cellulose films by the plasma formation during metal sputtering. Thus, the metal could be better integrated into the polymer films. The neural interfaces fabricated in this thesis project are considered as compliant interfaces for the human brain and spinal cord. They can adopt to the curvature of the tissue anatomy, withstand bending strain without losing conductivity, and provide long-term stability under physiological conditions even when cyclically loaded. These biocompatible implants are easy to handle during surgery. Their fabrication is time-effective, low-cost and compatible to large-scale production.