An Endothelium Membrane Mimetic Coating Enables Extracorporeal Membrane Oxygenation Without Systemic Anticoagulation

Thrombosis and bleeding are life-threatening complications in extracorporeal membrane oxygenation (ECMO) therapy. In this study, three covalently bonded heparin coatings, end-point-attached heparin (EPA-Hep), conventional multi-points anchored heparin (Hep), and a zwitterionic copolymer surface grafted heparin (PMPCC-Hep), were constructed on polydopamine pre-coated surfaces of ECMO circuits to explore more efficient and safer anticoagulation strategy. The EPA-Hep, Hep and PMPCC-Hep coating surfaces with decreased heparin densities of 3.0, 1.7 and 1.1 µg/cm2 showed increased protein resistances of 61, 76 and 92%, respectively. Moreover, all the coatings inhibited platelet adhesion and activation significantly and prolonged the activated partial thromboplastin time (APTT) remarkably to ≥260% of the control. Furthermore, coagulation factor inactivation efficacy and surface thrombosis resistance results support the highest anticoagulation ability of the PMPCC-Hep coating, which forming an endothelium membrane mimetic structure. More significantly, the PMPCC-Hep coated ECMO circuit performed a smooth and thrombosis-free oxygenation in 15 h pig extracorporeal circulation without any systemic anticoagulant, much better than the bare and Hep coated circuits with severe clots and plasma leakage in 4 h and 8 h, respectively. This bioactive heparin grafted bioinert cell membrane mimetic PMPCC coating strategy has great potential in developing more efficient and safer blood-contacting medical devices.