Evaluation of Novel Hemocompatible Surface Coatings for Extracorporeal Life Support: A Biocompatible Alternative to Systemic Anticoagulation

Extracorporeal life support (ECLS) is a class of technologies used to support or replace the function of failing organs. During ECLS, blood is withdrawn from systemic circulation and circulated through an artificial organ or “treatment membrane” that performs the function of the failing organ, prior to return to systemic circulation. While ECLS provides life-saving therapy to wide patient populations from pre-term infants to combat-wounded soldiers, this therapy is limited due to secondary thrombotic and bleeding complications that result from: 1) exposure of blood to the foreign surfaces in the device circuit and 2) administration of anticoagulant drugs to prevent clot formation in the circuit. In this study, we assessed a biomaterial solution to the challenge of hemostasis during ECLS by modifying surfaces in the circuit to improve compatibility with blood. This approach would provide local coagulation management at the blood-biomaterial interface, obviating the use of systemic anticoagulant drugs that cause secondary bleeding. We investigated a non-adhesive, liquid-infused coating called tethered liquid perfluorocarbon (TLP) that prevents plasma protein adsorption. We also investigated a metal-organic framework that catalyzes nitric oxide release from endogenous donors, localizing the platelet inhibitory effects of nitric oxide to the biomaterial surface as occurs in the endothelium. Our objective was to determine if these coatings were a robust biomaterials solution for ECLS without administration of anticoagulant drugs. We developed a three-step approach to assess the efficacy and safety of biomaterials for ECLS. First, materials were first evaluated in vitro in healthy donor blood using thromboelastography and platelet aggregometry. Second, we proceeded with evaluation of TLP applied to complete ECLS circuits in vivo using a swine model for 6 hours of circulation. We assessed thrombus formation by scanning electron microscopy, coagulation function using clinical tests, gas exchange performance of the membrane using pre- and post-membrane blood gases and assessed safety using vital signs and histology. Finally we evaluated TLP in a 72-hour intensive care unit study without supplemental anticoagulation utilizing similar methods as described in our 6 hour model, with additional analysis of mechanical ventilation settings, systemic cytokine expression, hematology and protein adhesion. We hypothesized that TLP would enable 72 hours of heparin-free ECLS by inhibiting protein adsorption, preventing thrombotic circuit occlusion and preserving native blood parameters; all without impeding membrane performance or causing systemic complications. Both TLP and the nitric oxide catalyst reduced the time and rate of thrombus initiation as well as clot strength ex vivo. The nitric oxide catalyst also reduced platelet aggregation. In our 6 hour evaluation, TLP applied to ECLS circuits reduced thrombus formation compared to control, heparin-coated circuits and did not affect gas transfer across the membrane lung or cause untoward effects. In our 72 hour evaluation, TLP failed to prevent thrombotic circuit occlusion, and additionally altered the performance of the membrane lung requiring greater support from the mechanical ventilator compared to control animals that received heparin-coated ECLS circuits with systemic anticoagulation therapy. We concluded that TLP is currently not an efficacious solution to permit ECLS for 72 hours without anticoagulant drugs. Future studies are needed that utilize the three-step assessment method we have developed here to evaluate multi-functional biomaterials with combined ability to prevent protein adsorption and inhibit platelet activation, such as occurs in the endothelium

Surface Modification of Oxygenator Fibers with a Catalytically Active Metal–Organic Framework to Generate Nitric Oxide: An Ex Vivo Pilot Study

Coating all portions of an extracorporeal membrane oxygenation (ECMO) circuit with materials exhibiting inherent, permanent antithrombotic properties is an essential step to prevent thrombus-induced complications. However, developing antithrombotic coatings for oxygenator fibers within membrane oxygenators of ECMO systems has proven challenging. We have used polydopamine (PDA) to coat oxygenator fibers and immobilize a Cu-based metal–organic framework (MOF) on the surface to act as a nitric oxide (NO) catalyst. Importantly, the PDA/MOF coating will produce NO indefinitely from endogenous S-nitrosothiols and it has not previously been applied to ECMO oxygenator fibers

A Clinical‐Scale Microfluidic Respiratory Assist Device with 3D Branching Vascular Networks

Abstract Recent global events such as COVID‐19 pandemic amid rising rates of chronic lung diseases highlight the need for safer, simpler, and more available treatments for respiratory failure, with increasing interest in extracorporeal membrane oxygenation (ECMO). A key factor limiting use of this technology is the complexity of the blood circuit, resulting in clotting and bleeding and necessitating treatment in specialized care centers. Microfluidic oxygenators represent a promising potential solution, but have not reached the scale or performance required for comparison with conventional hollow fiber membrane oxygenators (HFMOs). Here the development and demonstration of the first microfluidic respiratory assist device at a clinical scale is reported, demonstrating efficient oxygen transfer at blood flow rates of 750 mL min⁻1, the highest ever reported for a microfluidic device. The central innovation of this technology is a fully 3D branching network of blood channels mimicking key features of the physiological microcirculation by avoiding anomalous blood flows that lead to thrombus formation and blood damage in conventional oxygenators. Low, stable blood pressure drop, low hemolysis, and consistent oxygen transfer, in 24‐hour pilot large animal experiments are demonstrated – a key step toward translation of this technology to the clinic for treatment of a range of lung diseases