Blood oxygenation artificial lung membranes – three incremental modification strategies to improve hemocompatibility

The primary challenge in membrane-based artificial lung technology is the limited hemocompatibility, which often leads to thrombosis and hemolysis, threatening the patient's life. Ironically, despite safety concerns over perfluoroalkyl substances (PFAS), fluorochemicals exhibit irreplaceable amphiphobicity, resulting in superb long-term hemocompatibility. Therefore, for biomedical applications, it is important to impartially assess the toxicity of PFAS over short-term PFAS exposure for life-threatening situations. In this study, three incremental surface modification strategies—superhydrophobic, superamphiphobic, and slippery liquid-infused porous surface (SLIPS) coatings—were developed and systematically compared to enhance hemocompatibility without compromising oxygenation performance. Superhydrophobic modification onto cellulose acetate membranes provided improved blood repellency but was insufficient in mitigating protein adsorption and long-term coagulation. Superamphiphobic membranes, modified via perfluoroalkylsilane coatings on nanostructured surfaces, exhibited enhanced resistance to both aqueous and lipid fouling; the modification efficacy strongly depended on the carbon chain lengths. SLIPS coating, consisting of a tethered perfluorinated solid layer infused with a mobile perfluorocarbon liquid (FDA-approved as an artificial blood substitute), demonstrated outstanding antifouling and thromboresistant characteristics. Moreover, an ex vivo test using a 0.05 m² hollow fiber membrane module with a liquid-repellent coating demonstrated complete thrombus-free operation after circulation with porcine blood. These findings could provide a background dataset when assessing the advantages and disadvantages of PFAS for short-term medical intervention in life-threatening situations. Importantly, our data clearly conclude that PFAS-free SLIPS could be the optimal solution for next-generation artificial lung membranes.