Hemocompatibility challenge of membrane oxygenator for artificial lung technology

The artificial lung (AL) technology is one of the membrane-based artificial organs that partly augments lung functions, i.e. blood oxygenation and CO₂ removal. It is generally employed as an extracorporeal membrane oxygenation (ECMO) device to treat acute and chronic lung-failure patients, and the recent outbreak of the COVID-19 pandemic has re-emphasized the importance of this technology. The principal component in AL is the polymeric membrane oxygenator that facilitates the O₂/CO₂ exchange with the blood. Despite the considerable improvement in anti-thrombogenic biomaterials in other applications (e.g., stents), AL research has not advanced at the same rate. This is partly because AL research requires interdisciplinary knowledge in biomaterials and membrane technology. Some of the promising biomaterials with reasonable hemocompatibility - such as emerging fluoropolymers of extremely low surface energy - must first be fabricated into membranes to exhibit effective gas exchange performance. As AL membranes must also demonstrate high hemocompatibility in tandem, it is essential to test the membranes using in-vitro hemocompatibility experiments before in-vivo test. Hence, it is vital to have a reliable in-vitro experimental protocol that can be reasonably correlated with the in-vivo results. However, current in-vitro AL studies are unsystematic to allow a consistent comparison with in-vivo results. More specifically, current literature on AL biomaterial in-vitro hemocompatibility data are not quantitatively comparable due to the use of unstandardized and unreliable protocols. Such a wide gap has been the main bottleneck in the improvement of AL research, preventing promising biomaterials from reaching clinical trials. This review summarizes the current state-of-the-art and status of AL technology from membrane researcher perspectives. Particularly, most of the reported in-vitro experiments to assess AL membrane hemocompatibility are compiled and critically compared to suggest the most reliable method suitable for AL biomaterial research. Also, a brief review of current approaches to improve AL hemocompatibility is summarized. STATEMENT OF SIGNIFICANCE: The importance of Artificial Lung (AL) technology has been re-emphasized in the time of the COVID-19 pandemic. The utmost bottleneck in the current AL technology is the poor hemocompatibility of the polymer membrane used for O₂/CO₂ gas exchange, limiting its use in the long-term. Unfortunately, most of the in-vitro AL experiments are unsystematic, irreproducible, and unreliable. There are no standardized in-vitro hemocompatibility characterization protocols for quantitative comparison between AL biomaterials. In this review, we tackled this bottleneck by compiling the scattered in-vitro data and suggesting the most suitable experimental protocol to obtain reliable and comparable hemocompatibility results. To the best of our knowledge, this is the first review paper focusing on the hemocompatibility challenge of AL technology.