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

项目摘要 髋关节植入物（CI）电极阵列由铂丝和封装在硅橡胶外壳中的触点制成。 这些材料提供了对CI的长期功能至关重要的机械稳定性和柔韧性。然而，在这方面， 它们还引起可能具有有害影响的局部组织反应。例如，插入的创伤 CI可损害耳蜗健康和任何残余听觉。此外， 包裹CI电极阵列导致阻抗增加和信号分辨率降低，这降低了CI 有效性颅内纤维化也与听觉丧失有关， 植入后几年。因此，开发减轻插入创伤和炎症的材料， 对CI材料的纤维反应可显著改善器械功能和安全性。超低结垢 两性离子聚合物是一类新的材料，其显示出消除纤维化的显著前景。然而 作为散装材料，它们缺乏适用于CI的机械性能和长期耐久性。利用 两性离子聚合物的超低污垢表面特性，同时保持经证实的机械性能， 目前的CI材料的性能，我们最近建立了一种新的，专利的光化学过程， 在相关CI材料上同时聚合、接枝和交联两性离子薄膜。我们 现在利用最近开发的双网络聚合物技术的机械优势， 薄膜的强度。我们还使用薄膜作为新型药物输送平台， 持续动力学我们假设坚固的双网络两性离子薄膜涂层将保持长期稳定性。 长期防污性能;减少摩擦、插入创伤和颅内纤维化;并提供受控的 糖皮质激素的持续释放。因此，在目标1中，我们设计了稳健的双网络两性离子薄膜， 用于超低污染CI生物材料涂层的薄膜。目的2研究双网络、两性离子薄膜 使用人尸体对组织摩擦、插入力、耳蜗创伤和纤维化进行薄膜水凝胶CI涂层 绵羊模型最后，Aim 3开发了具有可控的、持续的 在报告小鼠CI模型中，使用糖皮质激素递送系统来减少脑内炎症和纤维化。 在植入的生物材料上开发坚固的两性离子薄膜涂层， 污垢，并能够控制和持续的药物输送代表了一个变革性的进步，以防止 创伤，减少纤维化，并改善与医疗器械放置相关的功能结果， 比如说CI

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.