Omniphobic Coating of Extracorporeal Life Support Systems for Improved Thromboresistance

项目总结 体外膜氧合(ECMO)常用于危重病监护病房的气体交换 严重呼吸和心力衰竭的事件。这种环路由一个或多个血管通路组成 由一束微孔中空纤维膜组成的套管、血泵和氧合器 (HFM)。血流通过泵从循环系统中抽出，并通过HFM束引导 在返回给患者之前进行充氧和二氧化碳清除。然而，ECMO具有较高的发病率 血栓形成和设备故障，与凝血级联激活有关，主要原因是 体外循环的非生物血液接触面。这种血栓形成在临床上表现出来。 如深静脉血栓形成、肺栓塞、氧合器血栓形成和小血管血栓形成。因此， 全身抗凝是必要的，这会导致出血和相关的并发症。ECMO- 伴发静脉血栓发生率高达85%，氧合器血栓发生率为10-16% 关于患者年龄和氧合器的设计。ECMO的严重出血率高达40%，其中16-21%是 颅内出血。尽管先进的生物材料得到了发展，ECMO的使用仍在继续 因出血和血栓并发症而受阻。 自由流医疗设备公司(FFMD)正在优化和商业化系留液体全氟碳(TLP) 医疗器械上的涂层。这个SBIR项目的目标是验证我们的TLP涂层的假设 ECMO膜可减少血栓形成。我们的长期目标是改善有需要的患者的预后 ECMO通过降低血栓形成和出血引起的并发症发生率。我们的全方位涂层 阻止所有生物成分(细菌、真菌、血液成分)附着在医用材料表面 通过固定一层薄薄的高度惰性和生物相容的全氟化液体来固定设备。我们的 优化的涂层技术在各种表面上结合了一层薄的含氟聚合物层，借助 化学气相沉积技术。 这个第一阶段提案的目标是获得概念上的证明，即我们的TLP氧合膜将 在临床相关条件下减少血栓形成。一旦获得概念证明，我们将 TLP氧合器cGMP生产进入第二阶段，继续FDA建议 生物兼容性测试，使其准备好上市前的批准。此第一阶段应用程序的目标是 通过调查以下具体目标来实现。目标1：优化PMP膜上的TP涂层以 保持其原有的微孔率和气体交换能力。目标2：优化LP涂层以实现 最高的血栓形成能力。目的3：测定优化的TLP涂层充氧材料的抗血栓性能 膜在ECMO相关流致剪应力作用下的平均使用时间。一次证明 的概念，我们将进行第二阶段的cGMP生产TLP氧合器和 并进行FDA推荐的生物相容性测试，以便为 上市前审批。

PROJECT SUMMARY Extracorporeal membrane oxygenation (ECMO) is commonly used in the critical care unit for gas exchange in the event of severe respiratory and cardiac failure. Such circuits consist of one or more vascular access cannulae, a blood pump, and an oxygenator composed of a bundle of microporous hollow fiber membranes (HFM). Blood flow is drawn from the circulatory system via a pump and directed through the HFM bundle for oxygenation and CO2 removal prior to being returned to the patient. However, ECMO has high incidence of thrombosis and device failure, which are associated with activation of the coagulation cascade primarily due to the non-biological blood-contacting surface of the extracorporeal circuit. Such thrombosis manifests clinically as deep vein thrombosis, pulmonary embolism, oxygenator thrombosis, and small vessel thrombosis. Hence, systemic anticoagulants are necessary, which leads to hemorrhage and associated complications. The ECMO- associated venous thrombosis rate is as high as 85% and oxygenator thrombosis rate is 10–16% depending on patient age and oxygenator design. ECMO has high severe hemorrhage rate of 40%, of which 16–21% is intracranial hemorrhage. Despite the development of advanced biomaterials, ECMO use continues to be hampered by bleeding and thrombosis complications. FreeFlow Medical Devices (FFMD) is optimizing and commercializing tethered liquid perfluorocarbon (TLP) coatings on medical devices. The goal of this SBIR project is to validate the hypothesis that our TLP-coated ECMO membranes will reduce thrombosis. Our long-term goal is to improve outcomes for patients requiring ECMO by reducing the rate of complications caused by thrombosis and bleeding. Our omniphobic coating stops the adhesion of all biological components (bacteria, fungi, blood components) to the surface of medical devices through the immobilization of a thin layer of highly inert and biocompatible perfluorinated liquid. Our optimized coating technology incorporates a thin fluoropolymer layer on various surfaces with the help of chemical vapor deposition technique. The objective of this phase I proposal is to obtain the proof of concept that our TLP-oxygenation membrane will reduce thrombogenicity under clinically relevant conditions. Once proof of concept has been obtained, we will progress to Phase II for cGMP manufacturing of TLP-oxygenator and proceed with FDA-recommended biocompatibility testing to make this ready for premarket approval. The goals of this phase I application will be achieved by investigating the following Specific Aims. Aim 1: Optimize TP coating on PMP membrane to maintain its original microporosity and gas exchange capacity. Aim 2: Optimize the LP coating to achieve the highest thrombogenicity. Aim 3: Determine thromboresistance of the optimized TLP-coated oxygenation membrane under ECMO-relevant flow-induced shear stress for the period of average use duration. Once proof of concept has been obtained, we will progress to Phase II for cGMP manufacturing of TLP-oxygenator and blood perfusion tubing and proceed with FDA-recommended biocompatibility testing to make this ready for premarket approval.