Reduction of Intracochlear Trauma and Fibrosis Using Dual Network, Zwitterionic Hydrogel Thin Films on Cochlear Implant Surfaces

Project Summary Cochlear implant (CI) electrode arrays are made of platinum wires and contacts encased in a silastic housing. These materials provide mechanical stability and flexibility critical to the long-term function of the CI. However, they also induce local tissue reactions that can have detrimental effects. For example, trauma from insertion of the CI can damage cochlear health and any residual acoustic hearing. Further, the fibrotic capsule that encases CI electrode arrays leads to increased impedances and decreased signal resolution which reduce CI effectiveness. Intracochlear fibrosis is also implicated in the loss of acoustic hearing that can occur months to years after implantation. Thus, developing materials that mitigate insertion trauma and the inflammatory, fibrous response to CI materials could significantly improve device function and safety. Ultra-low fouling zwitterionic polymers are a new class of materials that show significant promise to eliminate fibrosis. However as bulk materials they lack mechanical properties and long term durability suitable for use in CIs. To leverage the ultra-low fouling surface properties of zwitterionic polymers while maintaining the proven mechanical properties of current CI materials, we recently established a novel, patented photochemical process for simultaneous polymerization, grafting and cross-linking of zwitterionic thin films on relevant CI materials. We now leverage the mechanical advantages of recently developed dual network polymer technology to enhance the strength of the thin films. We also use the thin films as novel drug delivery platforms with controlled and sustained kinetics. We hypothesize that robust dual network, zwitterionic thin film coatings will maintain long- term anti-fouling properties; reduce friction, insertion trauma, and intracochlear fibrosis; and provide controlled sustained release of glucocorticoids. Accordingly, in Aim 1 we engineer robust, dual network zwitterionic thin films for ultra-low fouling CI biomaterial coatings. Aim 2 investigates the effect of dual network, zwitterionic thin film hydrogel CI coatings on tissue friction, insertion forces, cochlear trauma, and fibrosis using human cadaver and sheep models. Finally, Aim 3 develops zwitterionic thin film hydrogel coatings with controllable, sustained glucocorticoid delivery systems to reduce intracochlear inflammation and fibrosis in reporter mouse CI models. Development of robust zwitterionic thin film coatings on implanted biomaterials that are lubricious, ultra-low fouling, and capable of controlled and sustained drug delivery represents a transformative advance to prevent trauma, reduce fibrosis, and improve the functional outcomes associated with placement of medical devices, such as CIs, in the body.