Reduction of intracochlear fibrosis and bacterial infection using photopolymerized durable zwitterionic coatings on cochlear implant biomaterials

使用人工耳蜗生物材料上的光聚合耐用两性离子涂层减少耳蜗内纤维化和细菌感染

• 批准号: 10348137
• 负责人: Allan Guymon
• 金额: $ 44.01万
• 依托单位: UNIVERSITY OF IOWA
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-03-04 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10348137
• 关键词: Acoustics; Adherence; Adhesions; Adsorption; Astrocytes; Bacteria; Bacterial Adhesion; Bacterial Infections; Behavior; Biocompatible Materials; Cell Adhesion; Cell-Matrix Junction; Cells; Cicatrix; Clinical; Cochlea; Cochlear Implants; Crosslinker; Data; Development; Devices; Effectiveness; Engineering; Equilibrium; Excision; Fibroblasts; Fibrosis; Film; Friction; Growth; Hair Cells; Hearing; Housing; Image; Implant; Implanted Electrodes; In Vitro; Infection; Lead; Light; Masks; Measures; Mechanics; Medical Device; Membrane Proteins; Metals; Methods; Modulus; Molecular Weight; Monitor; Neurites; Neurons; Pattern; Performance; Periodicity; Photochemistry; Physiologic Ossification; Platinum; Polyethylenes; Polymers; Polyurethanes; Prevention; Process; Property; Proteins; Pseudomonas aeruginosa; Rattus; Reaction; Resistance; Safety; Schwann Cells; Signal Transduction; Silastic; Staphylococcus aureus; Staphylococcus epidermidis; Surface; Surface Properties; Technology; Testing; Thinness; Tissues; Titanium; Water; Width; bacterial resistance; base; capsule; cell growth; chemical group; crosslink; density; electric impedance; flexibility; functional outcomes; hearing impairment; implant associated infection; implant material; implantation; improved; improved functioning; in vivo; infection risk; learning materials; mechanical properties; medical implant; neuroprosthesis; new technology; novel; photopolymerization; polymerization; preservation; prevent; response; spiral ganglion; subcutaneous

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 device. However, they also induce local tissue reactions that can have detrimental effects. For example, the fibrotic capsule that encases CI electrode arrays leads to increased impedances and signal broadening which decreases the effectiveness of the device. Further, intracochlear fibrosis is implicated in the loss of acoustic hearing that can occur months to years after implantation. Beyond fibrosis, bacterial adhesion to CI materials can lead to infection and often requires removal of the CI. Thus, developing materials that mitigate the fibrous response and bacterial adhesion 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 and bacterial adhesion. 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 developed a novel photochemical process for simultaneous polymerization, grafting and cross-linking of durable zwitterionic thin films on relevant CI materials. We hypothesize that durable, cross-linked zwitterionic thin film coatings generated through photopolymerization will maintain long-term anti-fouling properties, direct cell growth, and dramatically reduce fibrosis and bacterial adhesion. In Aim 1, the effect of cross-link density on mechanical stability and durability will be examined by increasing molecular weight and concentration of the cross-linker. To elucidate the direct relationship between cross-link density and anti-fouling properties, protein adsorption and cell adhesion will be assessed. The inherent spatial control of photopolymerization enables precise patterning of the thin films. Accordingly, Aim 2 examines the effect of photopatterned zwitterionic coatings to spatially control cell adhesion (fibroblasts and astrocytes) and alignment (Schwann cells and spiral ganglion neurons, SGNs). Further, the impact of coating patterning on intracochlear fibrosis and ossification, hearing levels, and hair cell and SGN counts will be assessed. Finally, Aim 3 determines the ability of zwitterionic coatings to resist bacterial adhesion and persistence. The efficacy of these coatings on three different bacterial types, Staphylococcus aureus, Staphylococcus epidermidis, and Pseudomonas aeruginosa, will be assessed both in vitro and in vivo. Development of adherent and durable zwitterionic thin film coatings on polymers (e.g. silastic, polyurethanes, polyethylene, etc.) and metals (e.g. platinum, titanium, etc.) represents a transformative advance to improve the function and reduce the infection risk associated with placement of medical devices in the body.

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。 这些材料提供了对器械长期功能至关重要的机械稳定性和柔韧性。 然而，它们也会引起可能具有有害影响的局部组织反应。例如，纤维化 封装CI电极阵列的胶囊导致阻抗增加和信号增宽， 降低了装置的有效性。此外，耳蜗内纤维化与声传导损失有关。 植入后数月至数年内可能出现的听力障碍。除了纤维化，细菌粘附到CI材料上 可能导致感染，通常需要切除CI。因此，开发减轻纤维化的材料， 对CI材料的反应和细菌粘附可以显著改善装置功能和安全性。超- 低污垢两性离子聚合物是一类新的材料， 和细菌粘附。然而，作为散装材料，它们缺乏机械性能和长期耐久性 适合在CI中使用。为了利用两性离子聚合物的超低污垢表面特性， 为了保持当前CI材料的成熟机械性能，我们最近开发了一种新型 用于同时聚合、接枝和交联耐久两性离子薄膜的光化学方法 相关CI材料上的薄膜。我们假设耐用的交联两性离子薄膜涂层 通过光聚合产生的水将保持长期的防污性能，直接细胞生长， 显著减少纤维化和细菌粘附。在目标1中，研究了交联密度对机械性能的影响。 通过增加交联剂的分子量和浓度来检验稳定性和耐久性。 为了阐明交联密度和防污性能之间的直接关系， 并评估细胞粘附。光聚合的固有空间控制使得能够实现精确的聚合。 薄膜的图案化。因此，目标2考察了双图案化的两性离子涂层对 空间控制细胞粘附（成纤维细胞和星形胶质细胞）和排列（雪旺细胞和螺旋神经节 神经元，SGN）。此外，涂层图案化对脑内纤维化和骨化、听力、 水平，毛细胞和SGN计数将进行评估。最后，目标3确定了两性离子的能力， 涂层以抵抗细菌粘附和持久性。这些涂层对三种不同细菌的功效 金黄色葡萄球菌、表皮葡萄球菌和铜绿假单胞菌 无论是在体外还是在体内。在聚合物（例如聚乙烯）上的粘附性和耐久性两性离子薄膜涂层的开发 硅橡胶、聚氨酯、聚乙烯等）和金属（例如铂、钛等）代表了一种变革性的 改进功能，降低与医疗器械放置相关的感染风险， 身体