Slippery Omniphobic Coating for Hemodialysis Catheter to Improve Patency and Patient Outcomes

项目总结 在美国，大约80%的开始血液透析(HD)的患者在治疗时使用导管 2017年，18.6%的HD患者使用了导尿管。然而，隧道导尿管的使用 对于HD，血管通路与相对较高的并发症发生率有关，如血流不良和 导管功能障碍，导管功能障碍发生率为0.5~3.42次/1000导管/天。最多的 常见的导管相关问题是感染(导管相关血流感染；CRBSI)和 导管血栓形成。腔内血栓和纤维蛋白鞘形成所致的导管功能障碍 提供充分的透析，通常需要通过向血管内滴注溶栓剂进行抢救 导管管腔和/或导管交换。它会导致受累肢体的严重发病率，包括 肺栓塞和血栓形成后综合征。感染可由生物污垢和生物被膜引起 形成；每1000个导管日的比率从0.25到6.5不等，这导致了严重的发病率。CRBSI 可能会导致严重的并发症，如脊柱脓肿、心内膜炎和死亡。CRBSI经常要求 住院治疗，有时甚至留在重症监护室。然而，没有可用的解决方案来防止导管功能障碍 可以成功地预防血栓形成和感染。 FFMD已经开发出一种涂层技术，以创建系留液体全氟碳(TLP)表面，该表面 通过改善血栓形成、生物被膜形成、 和感染[3]。在两个步骤的过程中，一层薄薄的全氟化碳被化学结合并拴在一起 然后在HD导管的表面涂上一层可移动的薄层液体全氟碳层以产生 超强拒水TLP涂层。光滑的全氟碳涂料是独一无二的，因为它们在 导管和透析机中与临床相关的血流，防止血栓形成，防止 生物污垢。 这个第一阶段提案的目标是获得我们TLP涂层可以减少的概念证据 血液透析导管的血栓形成和防止生物膜的形成。一旦获得概念证明，我们 将进入cGMP生产和FDA推荐的生物兼容性测试的第二阶段申请 已准备好进行上市前审批。我们的目标是通过提高血管的长期通畅性来改善患者的预后 减少血栓形成和与CRBSI相关的并发症。

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 use of tunneled catheters for HD vascular access is associated with a relatively high incidence of complications such as poor flow and catheter 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 catheter thrombosis. Catheter dysfunction due to intraluminal thrombosis and fibrin sheath formation impairs the delivery of adequate dialysis and often requires salvage by instillation of a thrombolytic agent into the catheter lumen and/or catheter exchange. It leads to significant morbidity of the limbs involved, including pulmonary embolism, and post-thrombotic syndrome. Infections can be caused by biofouling and biofilm formation; rates vary from 0.25 to 6.5 per 1,000 catheter days, which results in significant morbidity. CRBSI can result in serious complications such as spine abscess, endocarditis, and death. CRBSI frequently requires hospitalization and sometimes even ICU stays. However, no available solutions to prevent catheter dysfunction can successfully prevent both thrombosis and infection. FFMD has developed a coating technology to create a tethered liquid perfluorocarbon (TLP) surface that reduces the complication rate with catheter use during HD by ameliorating thrombosis, biofilm formation, and infections [3]. In a two-step process, a thin layer of perfluorocarbon is chemically bound and tethered to the surface of the HD catheter and is then is coated with a mobile thin layer of liquid perfluorocarbon to yield a super-repellent TLP coating. Slippery perfluorocarbon coatings are unique because they remain stable under the clinically relevant blood flow seen in catheters and dialysis machines, resist thrombosis, and prevent biofouling. The objective of this phase I proposal is to obtain proof of concept that our TLP coating could reduce thrombogenicity and prevent biofilm formation in HD catheters. Once proof of concept has been obtained, we will progress to a Phase II application for cGMP manufacturing and FDA-recommended biocompatibility testing ready for premarket approval. Our goal is to improve patient outcomes by enhancing the long-term patency of HD catheters by reducing thrombosis and complications associated with CRBSI.