Omniphobic Coating of Extracorporeal Life Support Systems for Improved Thromboresistance

体外生命支持系统的全疏涂层可提高抗血栓能力

• 批准号: 10253612
• 负责人: Saibal Bandyopadhyay
• 金额: $ 22.39万
• 依托单位: FREEFLOW MEDICAL DEVICES, LLC
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-03-19 至 2022-09-18
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10253612
• 关键词: Acrylates; Adhesions; Adult; Advanced Development; Affect; Age; Anticoagulants; Bacteria; Biocompatible Materials; Biological; Blood; Blood Vessels; Blood flow; Cannulas; Carbon Dioxide; Cardiovascular system; Chemicals; Childhood; Citrates; Clinical; Coagulation Process; Critical Care; Cyclic GMP; Deep Vein Thrombosis; Deposition; Devices; Electrodes; Equipment Malfunction; Event; Excision; Exhibits; Extracorporeal Membrane Oxygenation; Failure; Fiber; Fibrinogen; Fluorine; Fluorocarbons; Future; Gases; Goals; Heart failure; Hemorrhage; Immobilization; In Vitro; Incidence; Industry Standard; Institutes; International; Intracranial Hemorrhages; Lead; Life Support Systems; Liquid substance; Medical; Medical Device; Membrane; Membrane Oxygenators; Oxygenators; Patient-Focused Outcomes; Patients; Performance; Phase; Phosphorylcholine; Physiological; Plasma; Plasma Proteins; Preparation; Process; Property; Pulmonary Embolism; Pump; Registries; Reporting; Resistance; Respiratory Failure; Roentgen Rays; Sheep; Small Business Innovation Research Grant; Solid; Spectrum Analysis; Surface; Techniques; Technology; Temperature; Testing; Thinness; Thrombosis; Thrombus; Time; Venous Thrombosis; biomaterial compatibility; blood perfusion; blood pump; clinically relevant; design; experience; experimental study; fungus; improved; improved outcome; in vivo evaluation; monomer; neonate; novel; prevent; shear stress; thrombogenesis; thrombotic complications; vapor

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.

项目摘要 体外膜氧合（ECMO）通常在重症监护单元中用于气体交换单位 严重的呼吸和心脏衰竭的事件。这样的圆圈由一个或多个血管通道组成 插管，血泵和由一束微孔空心纤维膜组成的氧合剂 （HFM）。血流是通过泵从电路系统中抽出的，并通过HFM捆绑包用于 在退还给患者之前，氧合和二氧化碳去除。但是，ECMO发生了很高的事件 血栓形成和装置故障，这与凝血级联反应有关，主要是由于 体外回路的非生物血液接触表面。这种血栓形成在临床上表现出来 作为深静脉血栓形成，肺栓塞，氧合血栓形成和小血管血栓形成。因此， 需要全身性抗凝剂，这会导致出血和相关并发症。 ecmo- 相关的静脉血栓形成率高达85％，氧合血栓形成率为10-16％ 关于患者的年龄和氧合设计。 ECMO的高严重出血率为40％，其中16-21％为 颅内出血。尽管发展了高级生物材料，但ECMO的使用仍在继续 受到出血和血栓形成并发症的阻碍。 FreeFlow Medical Devices（FFMD）正在优化和商业化束缚液体液氟化碳（TLP） 医疗设备上的涂料。这个SBIR项目的目的是验证我们的TLP涂层的假设 ECMO膜将减少血栓形成。我们的长期目标是改善需要的患者的结果 通过降低由血栓形成和出血引起的并发症发生率来通过ECMO。我们的混杂涂层 停止所有生物成分（细菌，真菌，血液成分）的粘附 通过固定高度惰性和生物相容性全氟化液的薄层的设备。我们的 优化的涂层技术在各种表面上结合了薄荧光聚合物层 化学蒸气沉积技术。 该阶段I建议的目的是获得概念证明，即我们的TLP氧合膜将 在临床相关条件下降低血栓形成。一旦获得了概念证明，我们将 进步到II期的CGMP制造TLP氧合器，然后进行FDA-RECONDEND 生物相容性测试可以使此事准备好上市的批准。 I阶段I应用程序的目标将是 目标1：优化PMP膜上的TP涂层到 保持其原始的微孔和气体交换能力。目标2：优化LP涂层以实现 最高的血栓形成性。 AIM 3：确定优化的TLP涂层的血栓抗性 在平均使用持续时间期间，在ECMO相关的流动诱导的剪切应力下，膜。一次证明 已经获得了概念，我们将前进到II阶段，用于CGMP的TLP氧合和 血液灌注管并进行FDA征用的生物相容性测试，以便为此做好准备 预售批准。