Micro-patterned surfaces for reducing the risk of catheter-associated UTI

描述(申请人提供)：仅在美国，每年就有近200万患者在医院感染，其中约10万人死亡。医院感染是美国主要的死亡原因，它们导致住院时间、人类痛苦和医疗费用的大幅增加。近一半的感染与使用医疗器械有关，导管相关性尿路感染(UTI)是最常见的医院感染类型，占医院和疗养院感染的40%以上。大约95%的尿路感染与导尿管有关，这些与导尿管相关的尿路感染每年的医院费用估计超过4亿美元。目前预防细菌性尿路感染的方法是引入抗菌剂，以减少与生物膜形成相关的细菌浓度。然而，抗菌剂的使用导致耐药模式，使留置导管感染更难治疗。通过涂覆导管，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。尽管预防策略取得了进展，但目前还没有明确的方法来预防导管相关性尿路感染。因此，Sharklet Technologies建议开发一种新的导管设计，能够持续抑制细菌生物膜的形成，而不依赖于传统的抗菌涂层或治疗。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的生长--其中鲨鱼的微图案是最有效的。因此，该项目的总体目标是开发、验证和商业化使用Sharklet显微模式(基于鲨鱼皮独特的防污染特性)，以在不使用抗菌剂的情况下抑制尿管上细菌生物膜的形成。具体目的是建议开发一种新的导管设计，能够持续抑制细菌生物膜的形成，而不依赖于传统的抗菌涂层或处理。建议开发一种新的导管设计，能够持续抑制细菌生物膜的形成，而不依赖于传统的抗菌涂层或治疗。建议开发一种新的导管设计，能够持续抑制细菌生物膜的形成，而不依赖于传统的抗菌涂层或治疗。第一阶段是1)验证Sharklet微图案聚合物表面在14天的过程中在生长介质和人工尿液中抑制致尿路致病性大肠埃希菌生物膜形成的有效性，以及2)证明制造呈现Sharklet图案的腔外和腔内表面的导管样原型的可行性。第一阶段的成功将验证使用微图案表面来防止尿路病原体的生物膜生长，并将证明构建展示该图案的导管样原型的可行性。后续的第二阶段项目将设计为开发试管原型的制造方法，并用活体猪模型展示效果。第一阶段和第二阶段SBIR数据将对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设备合作伙伴和分销商建立伙伴关系，特别是与尿管市场的合作伙伴和分销商。与公共卫生相关：在美国，每年有大约3000万根导尿管被插入500万名患者体内，由于导尿管表面形成的细菌生物膜，每个患者都有感染尿路的风险。目前抑制导管表面生物膜形成的方法价格昂贵，效果不佳，并且会导致严重的并发症，如毒副作用和多药耐药。该项目的总体目标是开发、验证和商业化使用Sharklet显微模式(基于鲨鱼皮独特的防污染特性)，以在不使用抗菌剂的情况下抑制尿管上细菌生物膜的形成。

DESCRIPTION (provided by applicant): In the U.S. alone, nearly two million patients acquire a nosocomial infection in the hospital each year, and approximately 100,000 of them die. Nosocomial infections are a leading cause of death in the U.S., and they result in major increases in hospital stays, human suffering, and healthcare costs. Nearly half of these infections are associated with the use of a medical device, and catheter-associated urinary tract infection (UTI) is the most common type of nosocomial infection, accounting for over 40% of infections in hospitals and nursing homes. Some 95% of UTIs are associated with urinary catheters, and these catheter-associated UTIs account for an estimated annual hospital cost of more than $400 million. The current paradigm for preventing bacterial UTIs has been to introduce antimicrobial agents to reduce the concentrations of bacteria associated with biofilm formation. However, use of antimicrobial agents leads to resistance patterns that make indwelling catheter infections more difficult to treat. By coating the catheter, the risk of infection is reduced; however, this strategy at best only delays the infection onset. Despite advances in prophylactic strategies, there are currently no definitive methods to prevent catheter-associated UTI. Sharklet Technologies therefore proposes development of a novel catheter design capable of sustained inhibition of bacterial biofilm formation that does not rely on traditional antimicrobial coatings or treatments. Preliminary studies have shown that micro-patterns on polymer surfaces can be designed to inhibit bacterial biofilm growth-with the Sharklet" micro-pattern being the most effective. Therefore, the overall goal of this project is to develop, validate, and commercialize the use of the Sharklet microscopic pattern (based on the unique antifouling characteristics of shark skin) to inhibit bacterial biofilm formation on urinary catheters without the use of antimicrobial agents. The Specific Aims for proposes development of a novel catheter design capable of sustained inhibition of bacterial biofilm formation that does not rely on traditional antimicrobial coatings or treatments. proposes development of a novel catheter design capable of sustained inhibition of bacterial biofilm formation that does not rely on traditional antimicrobial coatings or treatments. proposes development of a novel catheter design capable of sustained inhibition of bacterial biofilm formation that does not rely on traditional antimicrobial coatings or treatments. Phase I are 1) to validate the effectiveness of the Sharklet micro-patterned polymer surface for inhibiting biofilm formation with uropathogenic E. coli in growth media and artificial urine over the course of 14 days, and 2) to prove the feasibility of fabricating catheter-like prototypes that exhibit Sharklet-patterned extraluminal and intraluminal surfaces. Phase I success will validate the use of micro- patterned surfaces to prevent biofilm growth of a uropathogen and will demonstrate the feasibility of constructing a catheter-like prototype exhibiting the pattern. A follow-on Phase II project will be designed to develop manufacturing methods for the tube prototypes and to demonstrate efficacy with an in vivo pig model. The Phase I and Phase II SBIR data will be essential in attracting 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 urinary catheter markets. PUBLIC HEALTH RELEVANCE: Some 30 million urinary catheters are inserted into 5 million patients in the U.S. each year, and each one of those patients is at risk for acquiring a urinary tract infection due to the bacterial biofilms that form on the catheter surface. Current strategies for inhibiting biofilm formation on the catheter surfaces are expensive, ineffective, and give rise to serious complications such as toxic side-effects and multi-drug resistance. The overall goal of this project is to develop, validate, and commercialize the use of the Sharklet microscopic pattern (based on the unique antifouling characteristics of shark skin) to inhibit bacterial biofilm formation on urinary catheters without the use of antimicrobial agents.