Ogier, J. M.; Caballero-Aguilar, L. M.; Leeming, M. G.; Nisbet, D. R.; Nayagam, B. A.

Cochlear implants partially restore sound sensation for individuals with severe to profound hearing loss. This can significantly improve the recipients quality of life, largely through improved communication with spoken language. However, surgical trauma from electrode insertion also instigates biological responses that can compromise device performance and longevity. To address these limitations, we designed a novel polymer based coating that provides controlled release of selonsertib, an apoptosis signal regulating kinase 1 (ASK1) inhibitor with well described anti inflammatory, anti-fibrosis and cytoprotective properties. We describe the physical and molecular evaluation of this coating, including the application of next generation mass spectrometry based proteomics in mammalian cochlear explants and their culture medium. These analyses provide new insights into the acute tissue response in the damaged cochlea and demonstrate that selonsertib eluted from the polymer coating has a significant pro survival, anti inflammatory, and anti fibrosis effect. This study establishes proof of concept for selonsertib eluting polymers, demonstrating both feasibility for targeted drug delivery and efficacy for mitigating acute cochlear damage responses.