"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: 10672393
• 负责人: Tianhong Dai
• 金额: $ 21.53万
• 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/10672393
• 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; Fiber Optics; Growth; Haemophilus influenzae; Hair Cells; Hearing Tests; In Vitro; Incidence; Lasers; 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; Tube; Tympanometry; Tympanostomy; antimicrobial; biomaterial compatibility; cytotoxic; disilver oxide; effectiveness evaluation; efficacy evaluation; elastomeric; innovation; light emission; light scattering; microscopic imaging; middle ear; novel; optical emission; 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.

项目概要 鼓膜置管耳漏（TTO）是继鼓膜置管（TT）之后最常见的并发症 儿童安置。尽管使用外用抗生素进行标准治疗，但 TTO 常常持续存在或 反复发作。 TT 上的生物膜被认为是持续性和复发性 TTO 的主要原因。抗菌 蓝光（aBL）是一种创新的非药物方法，最近由于 通过光激发天然存在的内源性卟啉来发挥其突出的抗菌活性 细菌产生细胞毒性活性氧。在初步研究中，我们证明了aBL 能有效杀死实验生物膜中常见的 TTO 病原体。此 R21 提案的目标是 开发一种新型光学鼓膜造口管（Optical-TT），由生物相容性光散射材料制成 光学材料，从管的整个表面发射aBL，用于预防和治疗TTO。对此 最后，我们提出两个具体目标。 在目标 1 中，我们将进行体外研究，以确定 aBL 介导的 Optical-TT 在预防方面的功效 并根除由代表性 TTO 病原体形成的光学 TT 上的实验生物膜，包括 流感嗜血杆菌、金黄色葡萄球菌和铜绿假单胞菌。用于预防生物膜 Optical-TTs，Optical-TTs将在细菌接种后30分钟内使用aBL“激活”；同时为 为了根除生物膜，当管上的生物膜成熟后，光学-TT 将使用 aBL“激活”。这 Optical-TT 上生物膜的细菌负荷将通过定量菌落形成单位 (CFU) 计数来确定 和定性扫描电子显微镜 (SEM) 成像。 Optical-TT 的功效将是 与环丙沙星溶液和氧化银浸渍的Silicone TT 进行比较。 在目标 2 中，我们将进行临床前动物研究，以确定 aBL 介导的有效性和安全性 光学 TT 在龙猫实验性 TTO 预防和治疗中的应用。为了预防 TTO，光学-TT 细菌接种后30分钟内将被aBL“激活”；而对于 TTO 的治疗，Optical-TT 将 当通过鼓室导抗测试和耳显微镜观察到 TTO 时，可以使用 aBL“激活”TTO。细菌负荷 光学 TT 和中耳大泡将通过 CFU 计数和 SEM 成像来确定。功效 aBL 发现的结果将与环丙沙星/地塞米松滴耳剂的结果进行比较，后者是目前的 TTO 的护理立场。作为安全性研究，Optical-TT 对听觉功能的耳毒性将是 通过测量听觉大脑反应和耳蜗毛细胞存活率来确定。 总的来说，成功完成本提案中概述的具体目标将提供临床前 确定 aBL 介导的光学 TT 在预防和治疗方面的有效性和安全性所需的证据 TTO的治疗。研究还将展示 Optical-TT 原型系统的功能。