Extracorporeal membrane oxygenation (ECMO) is commonly used in the critical care unit for gas exchange inthe event of severe respiratory and cardiac failure. Such circuits consist of one or more vascular accesscannulae, 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 foroxygenation and CO2 removal prior to being returned to the patient. However, ECMO has high incidence ofthrombosis and device failure, which are associated with activation of the coagulation cascade primarily due tothe non-biological blood-contacting surface of the extracorporeal circuit. Such thrombosis manifests clinicallyas 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% dependingon patient age and oxygenator design. ECMO has high severe hemorrhage rate of 40%, of which 16-21% isintracranial hemorrhage. Despite the development of advanced biomaterials, ECMO use continues to behampered 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-coatedECMO membranes will reduce thrombosis. Our long-term goal is to improve outcomes for patients requiringECMO by reducing the rate of complications caused by thrombosis and bleeding. Our omniphobic coatingstops the adhesion of all biological components (bacteria, fungi, blood components) to the surface of medicaldevices through the immobilization of a thin layer of highly inert and biocompatible perfluorinated liquid. Ouroptimized coating technology incorporates a thin fluoropolymer layer on various surfaces with the help ofchemical vapor deposition technique.The objective of this phase I proposal is to obtain the proof of concept that our TLP-oxygenation membrane willreduce thrombogenicity under clinically relevant conditions. Once proof of concept has been obtained, we willprogress to Phase II for cGMP manufacturing of TLP-oxygenator and proceed with FDA-recommendedbiocompatibility testing to make this ready for premarket approval. The goals of this phase I application will beachieved by investigating the following Specific Aims. Aim 1: Optimize TP coating on PMP membrane tomaintain its original microporosity and gas exchange capacity. Aim 2: Optimize the LP coating to achieve thehighest thrombogenicity. Aim 3: Determine thromboresistance of the optimized TLP-coated oxygenationmembrane under ECMO-relevant flow-induced shear stress for the period of average use duration. Once proofof concept has been obtained, we will progress to Phase II for cGMP manufacturing of TLP-oxygenator andblood perfusion tubing and proceed with FDA-recommended biocompatibility testing to make this ready forpremarket approval.
Public Health Relevance Statement: PROJECT NARRATIVE
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.
Project Terms: Acrylates ; Adhesions ; Adult ; 21+ years old ; Adult Human ; adulthood ; Affect ; Age ; ages ; Anticoagulants ; Anticoagulant Agents ; Anticoagulant Drugs ; blood thinner ; thrombopoiesis inhibitor ; Bacteria ; Biocompatible Materials ; Biomaterials ; biological material ; Blood ; Blood Reticuloendothelial System ; Blood Vessels ; vascular ; Carbon Dioxide ; CO2 ; Carbonic Anhydride ; Cardiovascular system ; Cardiovascular ; Cardiovascular Body System ; Cardiovascular Organ System ; Heart Vascular ; circulatory system ; Citrates ; Critical Care ; Electrodes ; Exhibits ; Extracorporeal Membrane Oxygenation ; Fibrinogen ; Blood Coagulation Factor I ; Blood Coagulation Factor One ; Blood Factor One ; Coagulation Factor I ; Coagulation Factor One ; Factor I ; Factor One ; Fluorine ; F element ; Fluorocarbons ; Perfluorocarbons ; fungus ; Future ; Gases ; Goals ; Cyclic GMP ; Guanosine Cyclic Monophosphate ; cGMP ; Heart failure ; cardiac failure ; Hemorrhage ; Bleeding ; blood loss ; Immobilization ; orthopedic freezing ; In Vitro ; Incidence ; Institutes ; Lead ; Pb element ; heavy metal Pb ; heavy metal lead ; Life Support Systems ; Medical Device ; Oxygenators ; Membrane Oxygenators ; Patients ; Phosphorylcholine ; Choline Chloride Dihydrogen Phosphate ; Choline Phosphate ; Choline Phosphate Chloride ; Phosphocholine ; Phosphorylcholine Chloride ; Plasma ; Blood Plasma ; Plasma Serum ; Reticuloendothelial System, Serum, Plasma ; Plasma Proteins ; Pulmonary Embolism ; Registries ; Sheep ; Ovine ; Ovis ; Spectrum Analysis ; Spectroscopy ; Spectrum Analyses ; Technology ; Temperature ; Testing ; Thinness ; Leanness ; Thrombosis ; thrombotic disease ; thrombotic disorder ; Time ; Venous Thrombosis ; Phlebothrombosis ; Roentgen Rays ; X-Radiation ; X-Ray Radiation ; X-ray ; Xray ; Equipment Malfunction ; Device Failures ; Thrombus ; Deep Vein Thrombosis ; Deep-Venous Thrombosis ; Intracranial Hemorrhages ; blood pump ; Pump ; improved ; Surface ; Solid ; Clinical ; Phase ; Biological ; Physiological ; Physiologic ; Medical ; Chemicals ; Fiber ; Failure ; Childhood ; pediatric ; Blood flow ; fluid ; liquid ; Liquid substance ; Deposit ; Deposition ; Event ; Techniques ; Cannulas ; biocompatibility ; biomaterial compatibility ; experience ; membrane structure ; Membrane ; monomer ; Performance ; vapor ; blood perfusion ; novel ; Devices ; Reporting ; Abscission ; Extirpation ; Removal ; Surgical Removal ; resection ; Excision ; Property ; lung failure ; pulmonary failure ; Respiratory Failure ; shear stress ; preventing ; prevent ; Clotting ; Coagulation ; Coagulation Process ; International ; Patient-Focused Outcomes ; Patient outcome ; Patient-Centered Outcomes ; Small Business Innovation Research Grant ; SBIR ; Small Business Innovation Research ; Preparation ; Process ; neonate ; Advanced Development ; design ; designing ; Resistance ; resistant ; clinically relevant ; clinical relevance ; Industry Standard ; improved outcome ; experimental study ; experiment ; experimental research ; in vivo evaluation ; in vivo testing ; thrombogenesis ; thrombogenicity ; thrombotic complications ; thromboembolic complications ; thrombosis complications ;
