Reducing Infection and Plugging of Tympanostomy Tubes Through Zwitterionic Thin Films

通过两性离子薄膜减少鼓膜造口管的感染和堵塞

• 批准号: 10615107
• 负责人: Ryan Horne
• 金额: $ 5.27万
• 依托单位: UNIVERSITY OF IOWA
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-05-26 至 2024-05-25
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10615107
• 关键词: Adhesions; Affect; Bacteria; Bacterial Adhesion; Biocompatible Materials; Blood Platelets; Child; Complex; Conductive hearing loss; Devices; Dryness; Ear; Engineering; Eustachian Tube; Exposure to; Family suidae; Fibrinogen; Fibroblasts; Film; Fluorescence; Goals; Green Fluorescent Proteins; Health; Hydration status; Hydrogels; Implant; In Vitro; Infection; Intestines; Legal patent; Longevity; Macrophage; Measures; Methacrylates; Methods; Microbial Biofilms; Microscopy; Mission; Modification; Mucous body substance; National Institute on Deafness and Other Communication Disorders; Obstruction; Operative Surgical Procedures; Otitis Media; Otorrhea; Outcome; Periodic acid Schiff stain method; Physicians; Polyethylene Glycols; Polymers; Process; Property; Pseudomonas aeruginosa; Public Health; Rattus; Reader; Recurrence; Research; Resistance; Scientist; Stains; Standardization; Staphylococcus aureus; Staphylococcus epidermidis; Surface; Technology; Testing; Thinness; Training; Translational Research; Tube; Tympanic membrane; Tympanometry; Tympanostomy; United States National Institutes of Health; crosslink; density; effectiveness evaluation; experimental study; functional group; improved; in vitro Model; innovation; monomer; novel; patient subsets; polymerization; prevent; surface coating

PROJECT SUMMARY Although tympanostomy tube (TT or ear tube) placement is a simple and common surgery (754,000/year in the US), complications arise in a subset of patients, particularly post-TT otorrhea (PTTO, 26%) due to bacterial biofilms and mucus plugging (7-34%). There is an urgent need to reduce these complications and enhance the functional longevity of TTs. Modification of TT surfaces to prevent bacterial adhesion and to reduce mucus adhesion could dramatically reduce these complications. We recently developed a novel photochemically driven process that simultaneously forms and grafts zwitterionic thin films onto polymeric materials used to fabricate TTs (e.g. PDMS). These thin films are polymerized from either sulfobetaine methacrylate (SBMA) or carboxybetaine methacrylate (CBMA) monomers. The CBMA/SBMA polymer chains are crosslinked to each other during polymerization by polyethylene glycol dimethacrylate (PEGDMA). We find that both CBMA and SBMA thin films prevent adhesion by an order of magnitude from fibrinogen, platelets, macrophages, fibroblasts, and importantly, Staphylococcus aureus and Staphylococcus epidermidis. We propose to extend these promising findings into TTs, while determining how changes in crosslinking density affect end properties. The overall objective of this research is to determine the ability of zwitterionic thin films grafted onto the surface of TTs to prevent the complex phenomena of bacterial colonization and mucus plugging. We hypothesize that CBMA and SBMA zwitterionic thin films will prevent bacterial adhesion and reduce mucus plugging on TTs. We will test this hypothesis by undertaking the following Specific Aims. 1) Determine the effect of CBMA and SBMA thin films on bacteria adhesion from Staphylococcus aureus and Pseudomonas aeruginosa on TTs. We will test this effect by quantifying bacterial adhesion on PDMS surfaces using validated in vitro models. We will also expose rats that have been implanted with zwitterionic coated or bare TTs with either S. aureus or P aeruginosa to induce biofilm formation. 2) Investigate the ability of CBMA and SBMA thin films to reduce mucus adhesion, mucus drying, and mucus plug formation on TT surfaces. To test this, we will first examine the adhesion and drying of porcine intestinal mucus on PDMS that have been coated with thin films or remain uncoated. Finally, we will test the mucus plugging on coated and uncoated TTs inserted into rat tympanic membranes. When successful, these aims will implicate a novel and highly effective method to prevent common complications of TTs by preventing biofilm and mucus plug formation. Beyond TTs, the results will be broadly applicable to devices which suffer from biofouling. This innovation will reduce the PTTO complications currently suffered by ~50,000 US children per year and thus support the Mission, Goals, and Objectives of the NIDCD.

项目概要 尽管鼓室置管术（TT 或耳管）放置是一种简单且常见的手术（在美国每年有 754,000 例手术） US），一部分患者会出现并发症，特别是 TT 后耳漏（PTTO，26%）是由于细菌引起的 生物膜和粘液堵塞（7-34%）。迫切需要减少这些并发症并增强 TT 的功能寿命。 TT 表面改性以防止细菌粘附并减少粘液 粘附可以显着减少这些并发症。我们最近开发了一种新型光化学 驱动过程，同时形成两性离子薄膜并将其接枝到用于聚合材料上 制造 TT（例如 PDMS）。这些薄膜由磺基甜菜碱甲基丙烯酸酯 (SBMA) 或 羧基甜菜碱甲基丙烯酸酯（CBMA）单体。 CBMA/SBMA 聚合物链彼此交联 其他在聚乙二醇二甲基丙烯酸酯（PEGDMA）聚合过程中。我们发现 CBMA 和 SBMA 薄膜可防止纤维蛋白原、血小板、巨噬细胞、 成纤维细胞，重要的是金黄色葡萄球菌和表皮葡萄球菌。我们建议延长 将这些有希望的发现应用到 TT 中，同时确定交联密度的变化如何影响最终性能。 本研究的总体目标是确定两性离子薄膜接枝到表面的能力 TT 可以防止细菌定植和粘液堵塞的复杂现象。我们假设 CBMA 和 SBMA 两性离子薄膜可防止细菌粘附并减少 TT 上的粘液堵塞。我们 将通过实现以下具体目标来检验这一假设。 1) 确定CBMA和SBMA薄膜对金黄色葡萄球菌和细菌粘附的影响 TT 上的铜绿假单胞菌。我们将通过量化 PDMS 表面上的细菌粘附来测试这种效果 使用经过验证的体外模型。我们还将暴露已植入两性离子涂层或 裸露的 TT 与金黄色葡萄球菌或铜绿假单胞菌诱导生物膜形成。 2）研究CBMA和SBMA薄膜减少粘液粘附、粘液干燥和粘液的能力 TT 表面上的堵塞形成。为了测试这一点，我们首先检查猪肠道的粘附和干燥情况 已涂有薄膜或未涂敷的 PDMS 上的粘液。最后，我们将测试粘液 插入大鼠鼓膜的涂层和未涂层​​ TT 的堵塞。 如果成功的话，这些目标将意味着一种新颖且高效的方法来预防常见问题 通过防止生物膜和粘液栓形成来治疗 TT 并发症。除了 TT 之外，结果将广泛 适用于遭受生物污垢的设备。这项创新将减少目前的 PTTO 并发症 每年约有 50,000 名美国儿童遭受苦难，因此支持 NIDCD 的使命、目标和目的。