Novel Anti-infective and Anti-thrombotic Micro-patterned Central Venous Catheter

描述（由申请人提供）：医疗保健获得性感染的发生率和严重程度正在增加；作为美国十大主要死亡原因之一，它们对医学界构成了重大挑战。近一半的感染与医疗设备的使用有关。中心静脉导管（CVCs）是所有导管相关血流感染（crbsi）的约90%的原因。仅在美国，每年就有30万例感染与多达2.8万例死亡有关。crbsi延长了住院时间，给人带来痛苦，并增加了医疗成本（高达26.8亿美元）。导管相关性血栓形成（CRT）患者发生感染的可能性是其四倍，高达67%的CVC患者发生CRT。除了增加感染风险外，CRT还与血栓栓塞相关，血栓栓塞是美国院内死亡的主要原因。目前预防CRBSI和CRT的范例是引入抗菌剂或抗血栓药物来降低导管表面的细菌或血小板浓度。抗菌导管的活性可能会被高浓度的细菌淹没，其功效主要限于最初几天药物的初始洗脱高峰。抗凝剂涂层导管可能受到污染问题的影响，并没有显示出降低与血栓事件相关的死亡率。Sharklet Technologies Inc. （STI）旨在证明将我们专有的Sharklet微图案（Sharklet MP）集成到导管表面的可行性，以最终减少cvc相关感染，并验证Sharklet表面防止血小板粘附导致血栓形成的能力。STI的初步数据表明，Sharklet MP可以抑制细菌定植、血小板粘附和活化，从而具有双重预防CRBSI和CRT的能力。这个多阶段SBIR项目的总体目标是开发、验证和商业化Sharklet MP表面在下一代抗感染、抗血栓形成CVC上的应用。具体的I期目标是通过追求以下目标来显示Sharklet MP的有效性：1)证明我们可以在血管环境中延缓致病性葡萄球菌在Sharklet表面的定植，2)证明与未图案的对照表面相比，我们可以减少血小板粘附和随后在Sharklet表面形成的凝血酶。第二阶段的工作将集中在体内动物模型的验证、与其他病原体的体外测试、对有害药物化合物的耐久性测试以及Sharklet CVC的制造方法。第一和第二阶段的结果对于第三阶段与私营部门合作伙伴/投资者的合作至关重要，我们已经与他们讨论了这一应用程序。成功的多期SBIR的潜在影响将是生产新的Sharklet CVC，这将使临床医生/医院能够改善患者护理，并通过大大减少医院感染的主要负担和由血栓形成的住院死亡率来获得显著的成本节约。

DESCRIPTION (provided by applicant): Healthcare-acquired infections are increasing in rate and severity; they present a significant challenge to the medical community as a top-ten leading cause of death in the U.S. Nearly half of these infections are associated with the use of a medical device. Central venous catheters (CVCs) are responsible for approximately 90% of all catheter-related bloodstream infections (CRBSIs). The resulting 300,000 infections are associated with as many as 28,000 deaths per year in America alone. CRBSIs prolong hospital stays, induce human suffering, and magnify healthcare costs (up to $2.68 billion). Infection is four times more likely to occur in patients with catheter-related thrombosis (CRT), and up to 67% of patients with CVC develop CRT. In addition to increasing the risk of infection, CRT is associated with thromboembolic conditions that are the leading cause of in-hospital mortality in the U.S. The current paradigm for preventing CRBSI and CRT has been to introduce antimicrobial or antithrombotic agents to reduce the concentrations of bacteria or platelets on the catheter surface. The activity of antimicrobial catheters can be overwhelmed by high concentrations of bacteria, and their efficacy is primarily limited to the initial elution spike of agents in the first few days. Anticoagulant-coated catheters can suffer from contamination issues and have not been shown to reduce mortality rates associated with thrombotic events. Sharklet Technologies Inc. (STI) aims to demonstrate the feasibility of integrating our proprietary Sharklet micro-pattern (Sharklet MP) into catheter surfaces to ultimately reduce CVC-related infection and to validate the ability of the Sharklet surface to prevent platelet adhesion leading to thrombosis. STI's preliminary data demonstrates that the Sharklet MP inhibits bacterial colonization as well as platelet adhesion and activation-thereby offering a dual capacity to prevent CRBSI and CRT. The overall goal of this multi-phase SBIR project is to develop, validate, and commercialize the application of the Sharklet MP surface on a nextgeneration anti-infective, anti-thrombotic CVC. The specific Phase I goal is to show the efficacy of the Sharklet MP by pursuing the following Aims: 1) prove that we can retard pathogenic Staphylococci colonization on Sharklet surfaces in a vascular environment, and 2) prove that we can decrease platelet adhesion and subsequent thrombin formation on Sharklet surfaces compared to un-patterned control surfaces. Phase II work will then focus on validation with an in vivo animal model, in vitro testing with other pathogens, durability testing against deleterious drug compounds, and manufacturing methods for the Sharklet CVC. Phase I & II results are essential for Phase III collaboration with private-sector partners/investors with whom we are already discussing this application. The potential impact of a successful multi-phase SBIR will be the production of a new Sharklet CVC that will allow clinicians/hospitals to improve patient care and reap significant cost savings by substantially reducing the major burden of nosocomial infections and in-hospital mortality due to thrombosis. PUBLIC HEALTH RELEVANCE: The most serious and common complications of central venous catheters (CVC) are catheter-related bloodstream infection (CRBSI), which accounts for more than 30% of the deaths that result from hospital-acquired infections and incurs medical costs as high as $2 billion annually in the U.S. alone, and catheter-related thrombosis (CRT), which can lead to thromboembolism, a major contributor to in-hospital mortality. Unlike impregnation of the CVC surface with antimicrobial agents or coating with anticoagulants that have severe limitations in addressing CRBSI and CRT, a next-generation solution that incorporates the non-kill Sharklet" microscopic pattern onto the catheter surface can inhibit both bacterial colonization that leads to CRBSI and platelet adhesion that leads to CRT, thereby improving patient care. This multi-phase research effort will help develop and commercialize an anti-infective, anti-thrombotic CVC that has the Sharklet micro- pattern integrated on the catheter surface with the objective of improving patient safety by reducing in-hospital infection, morbidity, mortality, and costs.