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: 10321467
• 负责人: Ryan Horne
• 金额: $ 3.21万
• 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/10321467
• 关键词: Adhesions; Affect; Bacteria; Bacterial Adhesion; Biocompatible Materials; Blood Platelets; Child; Complex; Conductive hearing loss; Devices; 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; Longevity; 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; base; crosslink; density; effectiveness evaluation; experimental study; functional group; improved; in vitro Model; innovation; macrophage; monomer; novel; patient subsets; polymerization; prevent

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.

项目摘要 尽管鼓膜造口管（TT或耳管）位置是一种简单而常见的手术（每年为754,000 美国），一部分患者，尤其是细菌引起的TT Otorrhea（PTTO，26％）出现并发症 生物膜和粘液塞（7-34％）。迫切需要减少这些并发症并增强 TTS的功能寿命。修饰TT表面以防止细菌粘附并降低粘液 粘附可以大大减少这些并发症。我们最近在光化学上开发了一本小说 驱动过程同时形成并移植了zwitterionic薄膜到曾经的聚合物材料 制造TTS（例如PDMS）。这些薄膜是从甲基丙烯酸甲酯（SBMA）或 羧甲酰胺甲基丙烯酸酯（CBMA）单体。将CBMA/SBMA聚合物链交联 聚乙二醇二甲基酯（PEGDMA）聚合过程中的其他。我们发现CBMA和 SBMA薄膜可防止纤维蛋白原，血小板，巨噬细胞的数量级粘附， 成纤维细胞，重要的是金黄色葡萄球菌和表皮葡萄球菌。我们建议扩展 这些有希望的发现进入了TT，同时确定了交联密度的变化如何影响最终性质。 这项研究的总体目的是确定移植到表面 TT的tts，以防止细菌定植和粘液塞的复杂现象。我们假设这一点 CBMA和SBMA zwitterionic薄膜将防止细菌粘附并减少粘液塞在TT上。我们 将通过实现以下特定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 铜绿假单胞菌在TTS上。我们将通过量化PDMS表面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ZWITTRINIC涂层的大鼠或 带有金黄色葡萄球菌或P铜绿的裸露TT诱导生物膜形成。 2）研究CBMA和SBMA薄膜降低粘液粘附，粘液干和粘液的能力 插入TT表面上的插头。为了进行测试，我们将首先检查猪肠的粘附和干燥 PDM上涂有薄膜或保持未涂层的粘液。最后，我们将测试粘液 插入插入大鼠鼓膜膜中的涂层和未涂层​​的TT。 成功后，这些目标将暗示一种新颖而高效的方法来防止常见 通过防止生物膜和粘液塞形成TT的并发症。除了TT，结果将是广泛的 适用于患有生物污染的设备。这项创新将减少当前的PTTO并发症 每年约有50,000名美国儿童受苦，因此支持NIDCD的任务，目标和目标。