A nitric oxide-releasing organic selenium-grafted phosphorylcholine coating for thrombosis and inflammation prevention in extracorporeal membrane oxygenation

Abstract

Thrombosis and inflammation represent major challenges limiting the functionality of asymmetric poly(4-methyl-1-pentene) (PMP) hollow fiber membranes in extracorporeal membrane oxygenation (ECMO) systems. Moreover, the interplay between these two pathological processes can further exacerbate both coagulation and inflammatory responses. In this study, a dual-functional surface modification strategy was developed by first pre-functionalizing PMP hollow fiber membranes with selenocystamine, followed by grafting a phosphorylcholine copolymer MA(PCLA) to form a coating with combined anti-thrombotic and anti-inflammatory properties. Selenocystamine mimics endothelial nitric oxide release to suppress inflammatory responses, while MA(PCLA) mimics the structure of cell membranes to reduce protein adsorption and cellular adhesion. This approach is designed to provide a safer and more effective strategy for mitigating thrombotic and inflammatory complications. In vitro blood circulation assays demonstrated that the modified membranes exhibited significantly reduced protein adsorption, platelet adhesion, and thrombosis compared to both unmodified and commercially modified PMP membranes. Furthermore, both in vitro and in vivo experiments confirmed that the coating effectively modulates inflammatory cell differentiation and attenuates inflammatory responses. The dual-functional coating, exhibiting synergistic anti-thrombotic and anti-inflammatory effects, holds considerable promise for application in blood-contacting medical devices, particularly ECMO systems.