Real-Time Monitoring and Scavenging of Reactive Oxygen Species (ROS) to Enhance Cochlear Implantation Outcomes

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Project Summary Hearing loss is the third most common health condition, affecting people of all ages. For individuals who are deaf or have significant hearing loss, cochlear implants (CIs) are a standard treatment. CIs restore hearing by electrically stimulating residual viable auditory nerve fibers in the cochlea with an implanted electrode array. However, cochlear implantation is always accompanied by surgical injury, which initiates an acute inflammatory response to the electrode and induces on-set and progressive loss of residual acoustic hearing. Thus, there is an urgent need to develop a real-time monitoring method to help understand the neural conditions during and after implantation and subsequent hearing loss to enhance post-operative clinical outcomes. Inflammatory process induces oxidative stress (i.e. an elevated intracellular level of reactive oxygen species (ROS)) and reduces cellular antioxidant capacity. Numerous studies have shown that oxidative stress plays key roles for chronic neuroinflammation. Therefore, we hypothesize that oxidative stress is the major factor compromising CIs’ clinical outcome. In this R21 project, we propose to develop novel multifunctional CI electrodes and methods that can simultaneously monitor and scavenge initiation of the oxidative stress pathway during and after cochlear implantation. We will develop the multifunctional CIs to achieve real-time in vivo sensing and scavenging of ROS with clinically required sensitivity and specificity. Our approach to develop advanced multifunctional CIs is to utilize the unique palladium (Pd) and Pd bimetallic (i.e. Pd/Au) nanoparticles that show enzyme-like activities allowing sensitive and selective sensing of ROS as well as converting ROS to neutral molecules. In contrast to existing surface technologies for auditory neuronal protection and regeneration, our noble metal nanocatalysts as CIs electrodes are corrosion-resistant and biocompatible, and their unique surface electrochemistry can provide continuous (during and post-operative times) sensing and removal of ROS in vivo with high stability. The simultaneous neutralization of ROS with their electrochemical sensing reactions should mitigate oxidative stress-related cell death without disrupting the well- integrated innate antioxidant defense network, thus, improving post-operative clinical outcomes for individuals with CIs. In Aim 1, we will design and fabricate multifunctional CIs with bimetallic Pd/Au nanocatalysts integrated into a flexible parylene-based electrode array for detecting and scavenging ROS in vitro. In Aim 2, we will validate the detection and scavenging functions of the multifunctional CIs with an integrated microchannel in a rat model. Results from these pre-clinical development and validation studies in this R21 project will form the basis of a long-term R01 project to fully integrate sensing/scavenging capability into CI devices that are capable of recording, stimulation, sensing and scavenging functions for long-term clinical use. We also foresee the opportunities to apply the results gained here to other neural interfaces and medical implants. Our established multidisciplinary team with each member has more than 20 years’ experience with in vivo neuroprobe, real-time chemical sensor technology, and auditory neurophysiology respectively, making us well prepared to be successful in the proposed research activities.