"Optical Tympanostomy Tube" for prevention and treatment of tympanostomy tube otorrhea

“光学鼓膜置管”防治鼓膜置管耳漏

• 批准号: 10524834
• 负责人: Tianhong Dai
• 金额: $ 27.43万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-01 至 2024-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10524834
• 关键词: Address; Animals; Antibiotic Resistance; Antibiotics; Antimicrobial Resistance; Attention; Auditory; Auditory Threshold; Bacteria; Bacterial Antibiotic Resistance; Brain; Bulla; Caring; Cell Survival; Child; Chinchilla (genus); Ciprofloxacin; Clinical; Cochlea; Colony-forming units; Complication; Coupled; Development; Dexamethasone; Drainage procedure; Drops; Effectiveness; Elastomers; Electrons; Family; Fever; Growth; Haemophilus influenzae; Hair Cells; In Vitro; Incidence; Lasers; Lead; Light; Measurement; Measures; Mediating; Microbial Biofilms; Modeling; Observational Study; Odors; Optics; Otorrhea; Outcome; Pain; Patients; Porphyrins; Prevention; Production; Pseudomonas aeruginosa; Quality of life; Reactive Oxygen Species; Recurrence; Regimen; Reporting; Resistance development; Resistance profile; Safety; Scanning; Silicones; Staphylococcus aureus; Surface; System; Testing; Topical Antibiotic; Treatment Protocols; Tubal Occlusion; Tube; Tympanometry; Tympanostomy; antimicrobial; biomaterial compatibility; cytotoxic; disilver oxide; effectiveness evaluation; innovation; light scattering; microscopic imaging; middle ear; novel; optical fiber; ototoxicity; pathogen; pathogenic bacteria; polydimethylsiloxane; portability; pre-clinical; prevent; prospective; prototype; response; safety study; standard care; standard of care

PROJECT SUMMARY Tympanostomy tube otorrhea (TTO) is the most common complication after tympanostomy tube (TT) placement in children. Despite the standard treatment using topical antibiotics, TTO is often persistent or recurrent. Biofilms on TT are implicated to be the major cause of persistent and recurrent TTO. Antimicrobial blue light (aBL), an innovative non-pharmacological approach, has recently attracted increasing attention due to its prominent antimicrobial activity through photoexcitation of naturally occurring endogenous porphyrins in bacteria to produce cytotoxic reactive oxygen species. In the preliminary study, we demonstrated that aBL was effective in killing common TTO pathogens in experimental biofilms. The objective of this R21 proposal is to develop a novel Optical Tympanostomy Tube (Optical-TT), which is made from a biocompatible light-scattering optical material and emits aBL from the whole surface of tube, for prevention and treatment of TTO. To this end, we propose two Specific Aims. In Aim 1, we will perform in vitro studies to determine the efficacy of Optical-TT mediated by aBL in prevention and eradication of experimental biofilms on Optical-TTs formed by representative TTO pathogens, including Haemophilus influenzae, Staphylococcus aureus and Pseudomonas aeruginosa. For prevention of biofilms on Optical-TTs, Optical-TTs will be "activated" using aBL within 30 min after bacterial inoculation; while for eradication of biofilms, Optical-TTs will be "activated" using aBL after biofilms have matured on the tubes. The bacterial load of biofilms on Optical-TTs will be determined by quantitative colony-forming units (CFU) counting and qualitative scanning electron microscopic (SEM) imaging. The efficacy found with Optical-TT will be compared with those of ciprofloxacin solution and silver oxide-impregnated Silicone TT. In Aim 2, we will perform preclinical animal studies to determine the efficacy and safety of aBL-mediated Optical-TT in prevention and treatment of experimental TTO in chinchillas. For prevention of TTO, Optical-TT will be "activated" using aBL within 30 min after bacterial inoculation; while for treatment of TTO, Optical-TT will be "activated" using aBL when TTO are visible via tympanometry and otomicroscopy. The bacterial load on Optical-TTs and in the middle ear bullae will be determined by CFU counting and SEM imaging. The efficacy found with aBL will be compared with that of ciprofloxacin/dexamethasone otic drops, which are the current stand of care for TTO. As the safety study, the ototoxicity of Optical-TT to the auditory function will be determined by measurement of auditory brain response and hair cell survival in the cochlea. Collectively, successful completion of the Specific Aims outlined in this proposal will provide the preclinical evidence required to determine the effectiveness and safety of aBL-mediated Optical-TT in prevention and treatment of TTO. The studies will also demonstrate the functionality of a prototype system of Optical-TT.

项目摘要 鼓膜造口管耳状（TTO）是鼓膜造口管（TT）后最常见的并发症 安置在儿童中。尽管使用局部抗生素进行标准治疗，但TTO通常是持久的或 经常性。 TT上的生物膜被认为是持续和反复TTO的主要原因。抗菌 蓝光（ABL）是一种创新的非药理学方法，最近引起了越来越多的关注 通过光激发自然存在的内源性卟啉的显着抗菌活性 细菌产生细胞毒性活性氧。在初步研究中，我们证明了ABL是 有效地杀死实验生物膜中常见的TTO病原体。该R21提案的目的是 开发一种新型的光学鼓膜术管（光学TT），该管由生物相容性的光散射制成 光学材料并从整个试管表面排放ABL，以预防和处理TTO。对此 最后，我们提出了两个具体目标。 在AIM 1中，我们将进行体外研究，以确定ABL介导的预防光学TT的功效 并根除由代表性TTO病原体形成的光学TT的实验生物膜，包括 流感嗜血杆菌，金黄色葡萄球菌和铜绿假单胞菌。预防生物膜 光学TTS，光学TT将在细菌接种后30分钟内使用ABL“激活”；同时 生物膜根除生物膜后，将使用ABL“激活”生物膜在管子上成熟后。这 光学TT上生物膜的细菌负载将通过定量菌落形成单元（CFU）计数确定 和定性扫描电子显微镜（SEM）成像。光学TT发现的功效将是 与环丙沙星溶液和氧化物浸渍的有机硅TT的溶液相比。 在AIM 2中，我们将进行临床前动物研究以确定ABL介导的功效和安全性 在龙猫中预防和治疗实验TTO的光学TT。为了预防TTO，光学TT 在细菌接种后30分钟内，将使用ABL“激活”；在治疗TTO时，光学TT将 当TTO通过鼓膜法和耳鼻镜检查可见时，请使用ABL“激活”。细菌载荷 光学TT和中耳子中的Bullae将由CFU计数和SEM成像确定。功效 将ABL发现与环丙沙星/地塞米松的滴虫相比，这是电流 TTO的护理。作为安全研究，光学TT对听觉功能的耳毒性将是 通过测量听觉脑反应和耳蜗中的毛细胞存活来确定。 总的来说，该提案中概述的特定目标的成功完成将提供临床前 确定ABL介导的光学TT在预防和安全性方面的有效性和安全性所需的证据 TTO的处理。研究还将证明光学TT原型系统的功能。