Micro_patterned Surfaces for Reducing the Risk of Ventilator_Associated Pneumonia

描述（由申请人提供）：呼吸机相关性肺炎（VAP）是最昂贵和第二常见的医院获得性感染（HAI），占医院获得性肺炎（HAP）的86%以上。在美国，每年约有30万HAP患者接受治疗，据估计每年的医院费用超过15亿美元。目前预防VAP的范例是实施病人护理捆绑实践，并使用抗菌剂来减少细菌在试管表面的定植。然而，这些策略并没有表现出一致的功效或被广泛采用。一个主要问题是使用抗微生物药物导致耐药性模式，使感染更难以治疗。在这个多阶段的SBIR项目中，Sharklet Technologies因此建议通过开发、验证和商业化一种新型气管内管（ETT）设计来推进这一关键领域的最新技术，这种设计能够持续抑制生物膜，并且不依赖于传统的抗生素涂层。这项新技术是基于经过验证的鲨鱼图案表面，该表面已在以前的SBIR资助下成功开发。I期研究达到并超过了优化Sharklet模式的研究目标，并在富粘蛋白培养基和存在亚致死浓度抗生素等加剧生物膜生长的条件下，获得铜绿假单胞菌和MRSA细菌生物膜覆盖率至少降低50% （p<0.05）。这个多阶段SBIR项目的总体目标是进一步开发、验证和商业化使用仿生Sharklet微观模式来抑制ETT表面细菌生物膜的形成，而不使用抗菌剂。第二阶段的具体目标是：1)制造Sharklet微型图案的原型，以完成监管验证和验证测试；2)建立fda认可的体外呼吸机-气管内-肺模型，测试Sharklet微图ETT原型与临床分离的最常见VAP致病病原体对定植和生物膜形成的抑制作用；3)在绵羊模型中证明微生物定植、生物膜形成和管腔阻塞减少；4)在马萨诸塞州总医院外科ICU开展临床试点研究，以证明ETT定植、生物膜形成和管腔阻塞的减少。我们还将提交包含所有II期数据的510(k)，以获得器械级索赔。二期项目将由专业的跨学科研发团队进行

DESCRIPTION (provided by applicant): Ventilator-associated pneumonia (VAP) is the most costly and second most common hospital-acquired infection (HAI), accounting for over 86% of hospital-acquired pneumonia (HAP). Some 300,000 HAP patients are treated annually in the U.S., at an estimated annual hospital cost of more than $1.5 billion. The current paradigm for preventing VAP has been to implement patient care bundle practices and to use antimicrobial agents that reduce bacterial colonization on the tube surfaces. However, these strategies have not demonstrated consistent efficacy or widespread adoption. A major concern is the use of antimicrobial agents that lead to resistance patterns that make infections more difficult to treat. Under this multi-phase SBIR project, Sharklet Technologies therefore proposes to advance the state-of-the-art in this key area by developing, validating, and commercializing a novel endotracheal tube (ETT) design that is capable of sustained biofilm inhibition and that does not rely on traditional antibiotic coatings. This novel technology is based upon the proven Sharket-patterned surface that has been developed successfully under previous SBIR funding. Phase I studies met and exceeded research goals to optimize the Sharklet pattern and to obtain at least 50% reduction (p<0.05) of bacterial biofilm coverage of P. aeruginosa and MRSA in conditions that exacerbated biofilm growth such as mucin-rich media and presence of sub-lethal concentrations of antibiotics. The overall goal of this multi-phase SBIR project is to further develop, validate, and commercialize the use of the biomimetic Sharklet microscopic pattern to inhibit bacterial biofilm formation on the ETT surfaces without the use of antimicrobial agents. The Specific Aims for Phase II are to 1) manufacture prototypes of the Sharklet micro-pattern for completion of regulatory verification and validation testing; 2) carry out an FDA-recognized in vitro ventilator-endotracheal- lung model to test Sharklet micro-patterned ETT prototypes for inhibition of colonization and biofilm formation with clinical isolates of the most common VAP causative pathogens; 3) demonstrate reduced microbial colonization, biofilm formation, and lumen occlusion in a sheep model; and 4) carry out a clinical pilot study in the Massachusetts General Hospital's Surgical ICU to demonstrate reduced ETT colonization, biofilm formation and lumen occlusion. We will also submit a 510(k) with all of the Phase II data to obtain a device-level claim. The Phase II project will be carried out by the expert interdisciplinary R&D team that completed the Phase I work and that has completed successful Phase I and Phase II SBIR projects for NIH previously. Post-Phase II commercialization will involve scaled-up manufacturing methods for ETTs with Sharklet-patterned inner, outer, and cuff surfaces. The Phase II SBIR data will be essential in attracting and fully engaging industry partners with whom we are already discussing this technology (see letters).