Slippery Omniphobic Coating for Hemodialysis Catheter to Resist Fibrin Sheathing and Infection and Improve Patient Outcomes

用于血液透析导管的光滑全疏涂层可抵抗纤维蛋白鞘和感染并改善患者预后

基本信息

批准号：
10759575
负责人：
Todd McFarland
金额：
$ 80.19万
依托单位：
FREEFLOW MEDICAL DEVICES, LLC
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-08-01 至 2026-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10759575
关键词：
Acute Adhesions Adult Animals Back Bacteria Biological Blood Blood Circulation Blood Vessels Blood flow Candida Catheter-related bloodstream infection Catheters Cells Certification Clinical Complement Membrane Attack Complex Complication Cyclic GMP Cytolysis Device Safety Devices Dialysis procedure Domestic Sheep Effectiveness Engineering Euthanasia FDA approved Fibrin Fibrinogen Fluorocarbons Functional disorder Goals Good Manufacturing Process Hemodialysis Hemolysis Induction Histologic Hour Implant Incidence Indwelling Catheter Infection Liquid substance Manufacturer Marketing Medical Device Microbial Biofilms Pathway interactions Patient Care Patient-Focused Outcomes Patients Phase Polyurethanes Procedures Process Protocols documentation Recommendation Right atrial structure Route Secure Small Business Innovation Research Grant Staphylococcus aureus Staphylococcus epidermidis Sterilization Structure of jugular vein Superior vena cava structure Surface Technology Testing Thick Thinness Thrombosis Tissues Treatment Cost United States Veins Work biomaterial compatibility canine model commercialization cost design evaporation fungus genotoxicity hemocompatibility implantation improved improved outcome in vivo infection rate manufacture manufacturing process pathogen point of care preservation prevent prototype sheep model soluble complement C5b-9 systemic toxicity

项目摘要

PROJECT SUMMARY Approximately 80% of patients beginning hemodialysis (HD) in the United States use a catheter at treatment initiation, and 18.6% of all HD patients were using a catheter in 2017. However, the HD catheters (HDC) used for longer-term dialysis in patients have a high complication rate because of infections and dysfunction, with a catheter dysfunction rate of 0.5–3.42 episodes/1000 catheter-days. The most common catheter-related problems are infections (catheter-related bloodstream infections; CRBSI) and thrombosis. Fibrin sheath formation has a close relationship with pathogen colonization and biofilm formation on the catheter surface. The entry of pathogens into the bloodstream through the catheter-extraluminal and intraluminal routes and the seeding of pathogens that develop biofilm on the catheter surface cause CRBSI. In the US, annual HD treatment costs ~$89,000 per patient, with total costs of $42 billion. In 2016, 80% of patients used a catheter at initiation of HD and 18.6% of all HD patients in the US were using a catheter in 2017. However, no available solutions to prevent catheter dysfunction can successfully prevent both thrombosis and infection. FFMD is aiming to optimize and commercialize tethered liquid perfluorocarbon (TLP) coatings on medical devices. Our TLP coating stops the adhesion of all biological components (bacteria, fungi, blood components) to the surface of medical devices by immobilizing a thin layer of highly inert and biocompatible perfluorinated liquid. In preliminary work, we optimized our TLP coating technology for HDC by incorporating a thin fluoropolymer layer on the catheter surface. We also demonstrated that the optimized coating could reduce colonization by CRBSI pathogens by >85% vs. uncoated polyurethane catheter while also effectively reducing fibrinogen adhesion and thrombosis on the catheter surface. The objective of this Direct to Phase II SBIR application is to complete our path toward marketability with our TLP-modified HDC (TLP HDC). Using a previously established domestic sheep model, we will test the central hypothesis that TLP HDC will out-perform standard HDC by decreasing fibrin sheath formation, which has a close relationship with both catheter dysfunction and biofilm formation. This will be achieved using three aims. Aim 1: Compare the in vivo effectiveness of TLP HDC and standard HDC (Palindrome®) at reducing fibrin sheath formation and catheter tip occlusion. Aim 2: Obtain GMP-manufactured TLP HDC. Aim 3: Initiate the 510(k) application process to obtain FDA premarketing approval and perform a biocompatibility study. These advances will allow FFMD to maximize the effectiveness of the TLP coating and dramatically improve HD patient care by reducing catheter dysfunction and the CRBSI rate in clinical settings.

项目概要在美国，大约 80% 开始血液透析 (HD) 的患者在治疗时使用导管 2017 年，所有 HD 患者中有 18.6% 使用导管。然而，使用的 HD 导管 (HDC) 对于长期透析的患者来说，由于感染和功能障碍，并发症发生率很高，导管功能障碍率为 0.5–3.42 次/1000 导管日最常见的导管相关性。问题是感染（导管相关的血流感染；CRBSI）和纤维蛋白鞘。形成与导管表面病原体定植和生物膜形成有密切关系。病原体通过导管腔外和腔内途径进入血流以及在美国，每年发生 HD 的原因是在导管表面形成生物膜的病原体播散。每名患者的治疗费用约为 89,000 美元，总费用为 420 亿美元。2016 年，80% 的患者使用了导管。 HD 的开始，2017 年美国所有 HD 患者中有 18.6% 使用导管。然而，没有可用的数据预防导管功能障碍的解决方案可以成功预防血栓形成和感染。 FFMD 的目标是优化医疗领域的系留液体全氟化碳 (TLP) 涂层并将其商业化我们的 TLP 涂层可阻止所有生物成分（细菌、真菌、血液成分）的粘附。通过固定一薄层高度惰性和生物相容性的全氟化物到医疗设备的表面在前期工作中，我们通过加入薄层液体来优化 HDC 的 TLP 涂层技术。我们还证明，优化的涂层可以减少导管表面的含氟聚合物层。与无涂层聚氨酯导管相比，CRBSI 病原体的定植率提高了 >85%，同时还有效减少了纤维蛋白原在导管表面粘附和血栓形成。直接进入第二阶段 SBIR 申请的目标是通过我们的产品完成我们的市场化之路 TLP-modified HDC（TLP HDC）使用先前建立的家养绵羊模型，我们将测试中央。假设 TLP HDC 通过减少纤维蛋白鞘形成而优于标准 HDC，其具有与导管功能障碍和生物膜形成密切相关，这将通过三个目标来实现。目标 1：比较 TLP HDC 和标准 HDC (Palindrome®) 减少纤维蛋白的体内效果鞘形成和导管尖端闭塞目标 2：获得 GMP 制造的 TLP HDC 目标 3：启动向 FDA 申请 510(k) 流程，获得上市前批准并进行生物相容性研究。 FFMD 的进步将使 TLP 涂层的有效性最大化并显着提高 HD 通过减少临床环境中的导管功能障碍和 CRBSI 率来护理患者。