Micro-patterned Surfaces for Reducing the Risk of Ventilator-Associated Pneumonia

说明(申请人提供)：呼吸机相关肺炎(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，估计每年的医院费用超过15亿美元。目前预防VAP的范例是实施患者护理捆绑实践，并使用气管内管(ETT)技术，减少细菌进入管子表面并在管子表面定植。然而，这些策略不能持续抑制与VAP相关的细菌生物被膜；它们有限的有效时间阻碍了它们的价值--特别是对晚发型VAP，它更多地与耐药微生物种类有关。此外，使用抗菌剂会导致耐药模式，使感染更难治疗。通过在管子表面涂上涂层，感染的风险降低了；然而，这种策略充其量只会推迟感染的发生。目前还没有明确的方法来预防与多重耐药病原体相关的晚发性VAP。因此，Sharklet Technologies建议开发一种新的ETT设计，能够持续抑制生物膜，而不依赖于传统的抗生素涂层。初步研究表明，聚合物表面的微图案可以被设计成抑制细菌生物膜--其中鲨鱼的微图案是最有效的。因此，这一多阶段SBIR项目的总体目标是开发、验证仿生Sharklet显微模式并将其商业化，以在不使用抗菌剂的情况下抑制ETT管腔、袖口和外表面上细菌生物膜的形成。第一阶段的具体目标是1)优化Sharklet微模式的性能，以及2)在粘蛋白修饰的生长介质中用最常见的VAP病原体的临床分离株测试最有效的Sharklet微模式以抑制生物膜的形成，为期14天。(以前的项目已经证明了在内表面或外表面上制造具有鲨鱼图案的管的可行性。)后续的第二阶段项目将设计用于开发具有鲨鱼图案的内、外和袖带表面的ETT的放大制造方法，并通过活体动物模型进一步展示有效性。此外，第二阶段将提供一个机会来研究鲨鱼图案的ETT由于增强的表面能量而减少闭塞可能带来的额外好处，这将在体外粘液闭塞模型中进行研究。第一阶段和第二阶段SBIR数据对于吸引和充分吸引我们已经在与其讨论这项技术的“第三阶段”私营部门投资者和/或战略合作伙伴至关重要。因此，第三阶段的商业化工作将侧重于与医疗器械合作伙伴和分销商建立伙伴关系，特别是与ETT市场的合作伙伴和分销商。 公共卫生相关性：每个通过气管插管(ETT)接受机械通气的患者都有患呼吸机相关肺炎(VAP)的风险，VAP是第二种最常见的医院感染，死亡率很高，仅在美国每年就导致约15亿美元的医疗费用。鉴于这一问题的有效解决方案尚未被开发出来，特别是对于迟发性VAP，Sharklet Technologies，Inc.建议通过将其Sharklet“微观图案”整合到ETT组件上，以抑制导致细菌感染的生物膜形成并最终降低VAP的发生率，从而追求最先进的技术进步。这一多阶段的SBIR研究工作集中在开发/商业化Sharklet图案的ETT，它显著增强了当前ETT的设计，目标是提高患者的福利和安全性，同时大大降低医疗成本。

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 endotracheal tube (ETT) technologies that reduce bacterial access to and colonization on the tube surfaces. However, these strategies do not offer sustained inhibition of bacterial biofilm that is associated with VAP; their limited duration of efficacy hampers their value-particularly for late-onset VAP, which is more often associated with drug-resistant microbial species. Additionally, use of antimicrobial agents leads to resistance patterns that make infections more difficult to treat. By coating the tube surface, the risk of infection is reduced; however, this strategy at best only delays the infection onset. There are currently no definitive methods to prevent late-onset VAP associated with multi-drug-resistant pathogens. Sharklet Technologies therefore proposes to develop a novel ETT design capable of sustained biofilm inhibition that does not rely on traditional antibiotic coatings. Preliminary studies have shown that micro-patterns on polymer surfaces can be designed to inhibit bacterial biofilm-with the Sharklet" micro-pattern being the most effective. Therefore, the overall goal of this multi-phase SBIR project is to develop, validate, and commercialize the use of the biomimetic Sharklet microscopic pattern to inhibit bacterial biofilm formation on the ETT lumen, cuff, and outer surfaces without the use of antimicrobial agents. The Specific Aims for Phase I are to 1) optimize performance of the Sharklet micro-pattern, and 2) test the most effective Sharklet micro-patterns for inhibition of biofilm formation with clinical isolates of the most common VAP causative pathogens in a mucin-modified growth media over the course of 14 days. (Previous projects have already proven the feasibility of manufacturing tubes with the Sharklet pattern on the inner or outer surfaces.) A follow-on Phase II project will be designed to develop scaled-up manufacturing methods for ETTs with Sharklet-patterned inner, outer, and cuff surfaces and to further demonstrate efficacy with an in vivo animal model. Additionally, Phase II will offer an opportunity to investigate a possible added benefit of a Sharklet-patterned ETT-reduced occlusion due to enhanced surface energy, which will be studied in an in vitro mucus occlusion model. The Phase I and Phase II SBIR data will be essential in attracting and fully engaging the types of "Phase III" private-sector investors and/or strategic partners with whom we are already discussing this technology. Phase III commercialization efforts will therefore be focused on establishing partnerships with medical device partners and distributors-particularly those in the ETT markets. PUBLIC HEALTH RELEVANCE: Every patient who receives mechanical ventilation via an endotracheal tube (ETT) is at risk for developing ventilator-associated pneumonia (VAP)-the second most common hospital-acquired infection, which has a high mortality rate and results in medical costs of some $1.5 billion annually in the U.S. alone. Given that an effective solution to this problem has not been developed, particularly for late-onset VAP, Sharklet Technologies, Inc., proposes to pursue the needed advance in the state-of-the-art by incorporating its Sharklet" microscopic pattern onto the ETT components to inhibit biofilm formation that leads to bacterial infections and to ultimately reduce the incidence of VAP. This multi-phase SBIR research effort is focused on developing/commercializing a Sharklet-patterned ETT that significantly augments current ETT designs with the goal of increasing patient welfare and safety while greatly reducing medical costs.