Reducing Infection and Plugging of Tympanostomy Tubes Through Zwitterionic Thin Films

项目摘要 虽然鼓膜造孔管（TT或耳管）放置是一种简单而常见的手术（754，000/年， 美国），并发症出现在一个子集的患者，特别是后TT耳鼻喉（PTTO，26%）由于细菌感染， 生物膜和粘液堵塞（7-34%）。迫切需要减少这些并发症， TT的功能寿命。TT表面的改性以防止细菌粘附并减少粘液 粘连可以显著减少这些并发症。我们最近开发了一种新的光化学 同时形成两性离子薄膜并将其接枝到聚合物材料上的驱动方法， 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聚合物链交联到每个聚合物链上。 其它在聚合期间通过聚乙二醇二甲基丙烯酸酯（PEGDMA）。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。我们建议扩大 这些有前途的发现到TT，同时确定如何在交联密度的变化影响最终性能。 本研究的总体目标是确定两性离子薄膜接枝到表面上的能力 预防细菌定植和粘液堵塞的复杂现象。我们假设 CBMA和SBMA两性离子薄膜将防止细菌粘附并减少TT上的粘液堵塞。我们 我们将通过以下具体目标来检验这一假设。 1)确定CBMA和SBMA薄膜对来自金黄色葡萄球菌和金黄色葡萄球菌的细菌粘附的影响。 TT中的铜绿假单胞菌。我们将通过量化PDMS表面上的细菌粘附来测试这种效果 使用经验证的体外模型。我们还将暴露已经植入两性离子涂层或 裸TT与S.金黄色葡萄球菌或铜绿假单胞菌以诱导生物膜形成。 2)研究CBMA和SBMA薄膜减少粘液粘附、粘液干燥和粘液粘附的能力。 TT表面上的堵塞物形成。为了验证这一点，我们将首先检查猪小肠的粘附和干燥， PDMS上的粘液已经被薄膜涂覆或保持未涂覆。最后，我们将测试粘液 在插入大鼠鼓膜中的涂覆和未涂覆的TT上堵塞。 这些目标一旦成功，将为预防常见的 通过防止生物膜和粘液栓的形成来预防TT的并发症。除了TT，结果将广泛 适用于遭受生物污染的装置。这项创新将减少目前PTTO的并发症 每年约有50，000名美国儿童遭受这种疾病，因此支持NIDCD的使命、目标和目的。

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.