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.
Extracorporeal membrane oxygenators (ECMO) are used in the critical care unit to provide gas exchange in patients experiencing severe respiratory and cardiac failure; however, these devices have high rates of failure and thrombosis that can lead to a variety of significant and potentially fatal complications. We have developed a novel coating that can be applied to the membranes and tubing that make up ECMO devices to prevent thrombosis and ECMO failure. In this phase I proposal, we will obtain proof of concept that the coating successfully interferes with the processes leading to thrombosis in preparation for a future phase II application and application for pre-market approval.
