5:00 PM - SB05.06.03
Development of a Transient and Minimally Invasive Neural Interface
Adele Fanelli1,Laura Ferlauto2,Paola Vagni3,Katia Monsorno4,Elodie Zollinger1,Olivier Brina5,Philippe Reymond5,Paolo Machi5,Rosa Chiara Paolicelli4,Diego Ghezzi1
Ecole Polytechnique Federale de Lausanne1,Università di Bologna2,New York University3,Université de Lausanne4,Hôpitaux Universitaires de Genève5
Transient electronics enabling devices to safely disappear in the environment can be applied not only in green electronics, but also in bioelectronic medicine. Neural implants able to degrade harmlessly inside the body eliminate the need for removal surgery and potentially reduce inflammation responses and chronic adverse conditions that could hinder device functionality. The main limitation of current transient devices is their lifetime: fast degrading metals allow for operations rarely longer than a few days. To solve this problem, we propose an all-polymeric neural interface able to monitor neural activity for longer time scales. The device consists of a poly-ε-caprolactone (PCL) scaffold with patterned poly 3,4-ethylene dioxythiophene : polystyrene sulfonate (PEDOT:PSS) traces and electrodes. These metal-free electrodes showed a predominantly resistive behaviour with cut-off frequencies around 10Hz and a low impedance module maintaining noise levels below 10μV during in vivo neural recording for 12 weeks. Histological analysis highlighted the cellular infiltration inside the penetrating PCL scaffold over time, hinting to potential tissue remodelling processes, which would not occur with a non-degradable device. Moreover, a local cluster of activated microglia was found at the exposed electrode location, suggesting a specific interaction of these macrophages with the PEDOT:PSS. Looking closely, we found co-localization of activated microglia and fluorescent PEDOT:PSS. To better understand if microglia are able to degrade the conductive polymer, culture of BV2 microglial cells exposed to nanotubes (NTs) of PEDOT have been monitored over 24 hours and a decreasing trend of the amount of NTs has been noted. Further experiments taking into account potential roles of the reactive oxygen species produced by microglia in the degradation of PEDOT, will clarify its possible in vivo fate in the long term.
To increase the device potential for a clinical application, a minimally invasive procedure for its implantation has been proposed. The blood vasculature supplying the brain and nerves can be used as access route to the neural tissue, offering a close enough location without direct damage to the tissue. By using a stent-inspired design, the device can be navigated through a 5Fr (approx. 1.67mm) catheter and deployed in a 2mm-diameter channel. To avoid formation of blood thrombus, the device apposition to the wall must ensure small (< 180μm) gaps between itself and the vessel walls and allow for a minimal available lumen (50% of physiological). Microcomputed tomography scans of the device inside a channel revealed promising results with gaps of 98.1µm and lumen reduction of 18% of the original one. It must be noted that the channel used for these experiments was crafted from a rigid plastic cylinder: in a more realistic scenario the soft vasculature walls would accompany the expansion of the deployed device, possibly allowing a closer contact between the respective surfaces.
Electrodes’ endurance was monitored while exposed to a pulsatile flow of phosphate buffered saline at 37°C for 1 month: the impedance module increased over time, but values stayed lower than 100kΩ (500μm diameter). To evaluate the electrical stimulation ability of the device, endurance to continuous voltage transients has been tested and electrodes didn’t report any visible damage after 4M stimuli of 50nC-charge. Charge injection limits have been tested and the maximum injectable current was 5.2 ± 4.8 mA, similarly to what metallic stentrodes use for effective endovascular neurostimulation. In vivo testing and hemocompatibility evaluation will complete the characterization of the prototypes.
In conclusion, a minimally invasive surgical approach combined with long-lasting degradable materials could represent an attractive alternative to invasive permanent devices, by reducing inflammation risks and eliminating the need for removal surgeries.