Reducing Infection and Plugging of Tympanostomy Tubes Through Zwitterionic Thin Films

项目总结 虽然鼓室造瘘管(TT或耳管)的放置是一种简单和常见的手术(每年754,000 在美国)，部分患者出现并发症，特别是TT后耳漏(PTTO，26%)是由细菌引起的 生物被膜和粘液堵塞(7-34%)。迫切需要减少这些并发症，并加强 TTS的功能寿命。TT表面的改性以防止细菌粘连和减少粘液 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方法 同时在聚合物材料上形成并接枝两性离子薄膜的驱动过程，用于 制造TTS(例如，PDMS)。这些薄膜是由甲基丙烯酸磺基甜菜碱(SBMA)或 甲基丙烯酸羧甜菜碱(CBMA)单体。CBMA/SBMA聚合链分别交联化 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，以及重要的金黄色葡萄球菌和表皮葡萄球菌。我们建议延长 这些令人振奋的发现被用于TTS，同时确定了交联剂密度的变化如何影响末端性能。 这项研究的总体目标是确定两性离子薄膜接枝到表面的能力。 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连，减少粘液对TTS的堵塞。我们 将通过承担以下具体目标来检验这一假设。 1)测定CBMA和SBMA薄膜对金黄色葡萄球菌和 TTS上的铜绿假单胞菌。我们将通过量化细菌在PDMS表面的黏附来测试这种效果 使用经过验证的体外模型。我们还将暴露已被植入两性离子涂层或 裸露的TTS与金黄色葡萄球菌或铜绿假单胞菌一起诱导生物被膜形成。 2)研究CBMA和SBMA薄膜降低粘液粘连、粘液干燥和粘液的能力。 TT表面的堵塞层。为了测试这一点，我们将首先检查猪肠道的黏附和干燥 PDMS上的粘液，已被薄膜覆盖或仍未被涂层。最后，我们将测试粘液 对插入大鼠鼓膜的有涂层和无涂层的TTS进行封堵。 如果成功，这些目标将意味着一种新的、高效的方法来预防常见的 通过防止生物膜和粘液堵塞的形成来预防TTS的并发症。在TTS之外，结果将是广泛的 适用于遭受生物污垢的设备。这一创新将减少目前PTTO的并发症 每年约有50,000名美国儿童遭受痛苦，从而支持NIDCD的使命、目标和目标。

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.