Inhibition of Biofilms on Tympanostomy Tubes

描述(由申请人提供)：医疗植入物上细菌生物膜的形成是一个严重的临床问题。生物膜可以把一个简单的植入物变成严重的并发症。最近，我们发现，将微克有机硒共价附着到正畸装置的表面将抑制生物膜的形成，而不会产生有害的副作用。这导致了FDA最近(2009年)批准了可以放入儿童口腔的硒涂层正畸设备。这些设备现在正在市场上销售。使用硒来阻止细菌生物膜的使用是基于某些有机硒化合物以共价方式附着在材料上的独特能力，但仍然保持它们在表面催化产生超氧阴离子自由基的能力。然而，由于超氧自由基的半衰期很短，对设备附近的细胞没有影响。只要硒仍然附着在设备上，这个反应就会持续下去。测试表明，在高温下浸泡3个月后，该硒涂层仍具有完全的活性。硒对革兰氏阴性和革兰氏阳性病原菌以及白色念珠菌均有抑制作用。目前的应用是基于我们最近的发现，特定的有机硒化合物可以附着在硅胶鼓室造孔管上，从而抑制体外生物膜的形成。因此，提出了以下的具体目标：1.建立一种中试规模的有机硒覆盖鼓室造瘘管的方法，并将所得产物与中耳炎患者的分离株进行体外对照试验。2.研制硒涂层鼓室造瘘管，并在动物模型上测试其抑制生物膜形成和持续性耳漏的能力。。 公共卫生相关性：虽然鼓膜造孔管是治疗中耳积液的金标准，但它们的堵塞率在11%到25%之间，15%到50%的插管耳朵会发生耳漏。认为管材上生物膜的形成是耳漏和管子闭塞的主要因素。基于我们的发现，共价硒涂层将阻止鼓室造瘘管上生物膜的形成，我们建议测试涂有硒的鼓室造口管的抑制管堵塞和耳漏的能力。

DESCRIPTION (provided by applicant): Bacterial biofilm formation on medical implants is a serious clinical problem. Biofilms can turn a simple implant into a serious complication. Recently we showed that the covalent attachment of micrograms of organo-selenium to the surface of an orthodontic device will inhibit the formation of a biofilm without harmful side-effects. This has recently (2009) led to FDA approval for selenium coated orthodontic devices that can be placed into children's mouths. These devices are now on the market. The use of selenium to block bacterial biofilms is based upon the unique ability of certain organo-selenium compounds to be covalently attached to a material and yet still retain their ability to catalytically generate superoxide radicals on the surface. However, due to the short half-life of superoxide radicals, there are no effects on cells near the device. This reaction continues for as long as selenium remains attached to the device. Tests show that the selenium coating is still fully active after 3 months of soaking at an elevated temperature. Selenium inhibits gram negative and gram positive pathogenic bacteria as well as Candida albicans. The current application is based upon our recent findings that specific organo- selenium compounds can be attached to silicone tympanostomy tubes resulting in the inhibition of biofilm formation in vitro. Thus, the following specific aims are proposed: 1. To develop a pilot scale method to coat tympanostomy tubes with organo-selenium and test the resulting product in vitro against isolates obtained from otitis media patients. 2. To develop and test selenium coated tympanostomy tubes in an animal model for their ability to inhibit biofilm formation and persistent otorrhea. . PUBLIC HEALTH RELEVANCE: While tympanostomy tubes are the gold standard for treatment of otitmis media and effusion, their occlusion rate is between 11 and 25%, and otorrhea occurs in 15-50% of tube inserted ears. It is felt that biofilms forming on the tube material is the main factor in the development of otorrhea and tube occlusion. Based upon our findings that a covalent selenium coating will block biofilm formation on tympanostomy tubes, we propose testing selenium-coated tympanostomy tubes for their ability to inhibit tube occlusion and otorrhea.