Prevention of catheter related infections via photoactive nitric oxide delivery device

通过光敏一氧化氮输送装置预防导管相关感染

• 批准号: 10753081
• 负责人: Elizabeth Joy Brisbois
• 金额: $ 40.34万
• 依托单位: UNIVERSITY OF GEORGIA
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-01 至 2027-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10753081
• 关键词: Adhesions; Anti-Bacterial Agents; Antibiotics; Anticoagulation; Antimicrobial Effect; Bacteremia; Bacteria; Bacterial Infections; Binding; Bioreactors; Blood; Blood Circulation; Blood Platelets; Blood Vessels; Blood-Borne Pathogens; Catheter-related bloodstream infection; Catheters; Cell Line; Cells; Cessation of life; Clinical; Coagulation Process; Conscious; Development; Device Designs; Devices; Disinfection; Embolism; Exposure to; Fiber Optics; Generations; Goals; Health Care Costs; Healthcare Industry; Heparin; Hour; Immobilization; In Vitro; Indwelling Catheter; Infection; Infection prevention; Intensive Care Units; Klebsiella pneumoniae; Lead; Legal patent; Length; Life; Local Anti-Infective Agents; Measures; Medical; Medical Device; Microbial Biofilms; Modeling; N-acetylpenicillamine; Nitric Oxide; Nitric Oxide Donors; Obstruction; Oryctolagus cuniculus; Patient Care; Patients; Peripheral; Physiological; Platelet Activation; Polymers; Prevention; Property; Pseudomonas aeruginosa; Research Project Grants; Risk; S-Nitrosothiols; Safety; Sepsis; Side; Staphylococcus aureus; Staphylococcus epidermidis; Sterilization; Surface; Technology; Testing; Therapeutic; Thrombosis; Thrombus; Translations; United States; Vascular Endothelial Cell; Venous; Work; analytical method; antimicrobial; biomaterial compatibility; catheter related infection; clinical application; clinical translation; cost; covalent bond; data integration; early phase clinical trial; hemocompatibility; implantable device; improved; in vitro Bioassay; microbial; migration; optical fiber; photoactivation; portability; prevent; success; thrombotic; thrombotic complications

Project Summary/Abstract Currently, clinical applications of intravascular catheters suffer from major challenges: 1) infection; and 2) platelet activation and surface-induced thrombosis. Bacterial contamination of catheters causes more than 28,000 deaths per year in the United States, as well as costing the healthcare industry a staggering $2.3 billion. Thrombus formation can further lead to obstruction of blood vessels, catheter malfunction, or even life- threatening situations such as embolism. Commercial catheters with heparin-bonded surfaces are available to prevent clotting, but do little to prevent infections. In addition, antiseptics or antibiotics catheter coatings or lock solutions decrease the risk of bacterial infection, but do not prevent biofilm formation that shields bacteria from antibiotics. Therefore, there is a necessity and opportunity to develop device strategies for preventing infection and thrombosis on indwelling catheters for enhanced patency and safety. Our work and others have demonstrated that nitric oxide (NO) release from polymer surfaces can prevent platelet activation and bacterial infection. This technology mimics the vascular endothelial cells lining the blood vessels, as well as other cells in our bodies, producing NO locally to prevent clotting and bacterial biofilm. Recently we discovered that all of the positive effects can be achieved from polymers physically blended with the NO donor molecule S-nitroso-N-acetylpenicillamine (SNAP), which is nontoxic, inexpensive, and easy to synthesize. Active NO release from the NO donors in polymers reduces infection and thrombosis on catheters; however, the NO-release polymer strategy alone is limited by the finite reservoir of NO donor functionalities within the catheter wall which limits the duration of the NO availability/release. Our recent work has shown the potential of developing a catheter hub device that utilizes photoactive NO-releasing polymers with side glowing fiber optics that enables controllable NO release levels. The goal of this proposal is to develop a catheter hub device comprised of a polymer utilizing a NO donor covalently bonded to the polymer with side glowing fiber optics to provide photoactive NO-release (without leaching) to provide long-term, tunable NO-release at the catheter interface to provide potent broad-spectrum antimicrobial properties and reduce thrombosis by inhibiting platelet adhesion/activation. The new device will be applicable to any catheter device; however, this proposal will focus on studying the combined photoactive NO-releasing catheter hub device in long-term intravascular catheters for the prevention of infection and thrombosis. Successful completion of this project will allow progression to early clinical trials and the development of a new generation of devices that can be inserted within the lumen of indwelling catheters to prevent these complications while improving patient care.

项目概要/摘要 目前，血管内导管的临床应用面临主要挑战：1）感染； 2) 血小板 活化和表面诱导的血栓形成。导管细菌污染导致28000余起 美国每年造成的死亡人数高达 23 亿美元，医疗保健行业也因此损失了惊人的 23 亿美元。 血栓形成可进一步导致血管阻塞、导管故障，甚至危及生命。 威胁情况，例如栓塞。具有肝素粘合表面的商业导管可用于 防止凝血，但对预防感染作用不大。此外，防腐剂或抗生素导管涂层或锁 解决方案可降低细菌感染的风险，但不能阻止生物膜的形成，从而保护细菌免受感染 抗生素。因此，有必要和机会开发预防感染的器械策略 以及留置导管上的血栓形成，以提高通畅性和安全性。 我们和其他人的工作已经证明，从聚合物表面释放一氧化氮 (NO) 可以阻止血小板聚集 激活和细菌感染。这项技术模仿血管内壁的血管内皮细胞， 以及我们体内的其他细胞，局部产生一氧化氮以防止凝血和细菌生物膜。最近我们 发现所有积极效果都可以通过与 NO 供体物理混合的聚合物来实现 分子S-亚硝基-N-乙酰青霉胺（SNAP），无毒、廉价且易于合成。 聚合物中 NO 供体释放的活性 NO 减少了导管上的感染和血栓形成；然而， 单独的 NO 释放聚合物策略受到导管内有限的 NO 供体功能库的限制 限制 NO 可用性/释放持续时间的墙。我们最近的工作表明了潜力 开发一种导管毂装置，该装置利用光活性 NO 释放聚合物和侧发光光纤 从而实现可控的 NO 释放水平。该提案的目标是开发一种导管毂装置 由聚合物组成，利用 NO 供体与侧发光纤维共价键合 光学器件提供光敏 NO 释放（无浸出），以提供长期、可调节的 NO 释放 导管接口提供有效的广谱抗菌特性并减少血栓形成 通过抑制血小板粘附/活化。新装置将适用于任何导管装置；然而， 该提案将重点长期研究组合式光活性NO释放导管毂装置 血管内导管用于预防感染和血栓形成。该项目的顺利完成将 允许进行早期临床试验并开发新一代可插入的设备 在留置导管的管腔内，可以预防这些并发症，同时改善患者护理。