title: Endothelialization and characterization of titanium dioxide-coated gas-exchange membranes for application in the bioartificial lung.
abstract: Fouling on the gas-exchange hollow-fiber membrane (HFM) of extracorporeal membrane oxygenation (ECMO) devices by blood components and pathogens represents the major hurdle to their long-term application in patients with lung deficiency or unstable hemodynamics. Although patients are treated with anticoagulants, deposition of blood proteins onto the membrane surface may still occur after few days, leading to insufficient gas transfer and, consequently, to device failure. The aim of this study was to establish an endothelial cell (EC) monolayer onto the gas-exchange membrane of an ECMO device with a view to developing a hemocompatible bioartificial lung. Poly(4-methyl-1-pentene) (PMP) gas-exchange membranes were coated with titanium dioxide (TiO2), using the pulsed vacuum cathodic arc plasma deposition (PVCAPD) technique, in order to generate a stable interlayer, enabling cell adhesion onto the strongly hydrophobic PMP membrane. The TiO2coating reduced the oxygen transfer rate (OTR) of the membrane by 22%, and it successfully mediated EC attachment. The adhered ECs formed a confluent monolayer, which retained a non-thrombogenic state and showed cell-to-cell, as well as cell-to-substrate contacts. The established monolayer was able to withstand physiological shear stress and possessed a "self-healing" capacity at areas of induced monolayer disruption. The study demonstrated that the TiO2coating mediated EC attachment and the establishment of a functional EC monolayer.
  
  
  
  Surface endothelialization is considered an effective approach to achieve complete hamocompatibility of blood-contacting devices. Several strategies to enable endothelial cell adhesion onto stents and vascular prostheses have already been described in the literature. However, only few studies investigated the feasibility of establishing an endothelial monolayer onto the gas exchange membrane of ECMO devices, using peptides or proteins that were weakly adsorbed via dip coating techniques. This study demonstrated the effectiveness of an alternative and stable titanium dioxide coating for gas-exchange membranes, which enabled the establishment of a confluent, functional and non-activated endothelial monolayer, while maintaining oxygen permeability.
authors.affiliation: Department of Cardiothoracic, Transplantation and Vascular Surgery, Hannover Medical School, 30625 Hannover, Germany; Leibniz Research Laboratories for Biotechnology and Artificial Organs, Hannover Medical School, 30625 Hannover, Germany. Electronic address: pflaum.michael@mh-hannover.de.
authors.forename: Michael
authors.initials: M
authors.lastname: Pflaum
authors.affiliation: Institute for Plasmatechnology and Mathematics, University of Federal Armed Forces, 85577 Neubiberg, Germany.
authors.forename: Marina
authors.initials: M
authors.lastname: Kühn-Kauffeldt
authors.affiliation: Department of Cardiothoracic, Transplantation and Vascular Surgery, Hannover Medical School, 30625 Hannover, Germany; Leibniz Research Laboratories for Biotechnology and Artificial Organs, Hannover Medical School, 30625 Hannover, Germany.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Schmeckebier
authors.affiliation: Department of Cardiothoracic, Transplantation and Vascular Surgery, Hannover Medical School, 30625 Hannover, Germany; Leibniz Research Laboratories for Biotechnology and Artificial Organs, Hannover Medical School, 30625 Hannover, Germany.
authors.forename: Daniele
authors.initials: D
authors.lastname: Dipresa
authors.affiliation: Department of Cardiothoracic, Transplantation and Vascular Surgery, Hannover Medical School, 30625 Hannover, Germany; Leibniz Research Laboratories for Biotechnology and Artificial Organs, Hannover Medical School, 30625 Hannover, Germany.
authors.forename: Kanchan
authors.initials: K
authors.lastname: Chauhan
authors.affiliation: Department of Cardiothoracic, Transplantation and Vascular Surgery, Hannover Medical School, 30625 Hannover, Germany; Leibniz Research Laboratories for Biotechnology and Artificial Organs, Hannover Medical School, 30625 Hannover, Germany; German Centre of Lung Research, 30625 Hannover, Germany.
authors.forename: Bettina
authors.initials: B
authors.lastname: Wiegmann
authors.affiliation: Institute for Solid State Physics, Leibniz University Hannover, 30167 Hannover, Germany.
authors.forename: Rolf J
authors.initials: RJ
authors.lastname: Haug
authors.affiliation: Institute for Plasmatechnology and Mathematics, University of Federal Armed Forces, 85577 Neubiberg, Germany.
authors.forename: Jochen
authors.initials: J
authors.lastname: Schein
authors.affiliation: Department of Cardiothoracic, Transplantation and Vascular Surgery, Hannover Medical School, 30625 Hannover, Germany; Leibniz Research Laboratories for Biotechnology and Artificial Organs, Hannover Medical School, 30625 Hannover, Germany; Lower Saxony Centre for Biomedical Engineering, Implant Research and Development, 30625 Hannover, Germany; German Centre of Lung Research, 30625 Hannover, Germany.
authors.forename: Axel
authors.initials: A
authors.lastname: Haverich
authors.affiliation: Department of Cardiothoracic, Transplantation and Vascular Surgery, Hannover Medical School, 30625 Hannover, Germany; Leibniz Research Laboratories for Biotechnology and Artificial Organs, Hannover Medical School, 30625 Hannover, Germany; Lower Saxony Centre for Biomedical Engineering, Implant Research and Development, 30625 Hannover, Germany.
authors.forename: Sotirios
authors.initials: S
authors.lastname: Korossis
mesh_terms: D021522:Bioartificial Organs; D001792:Blood Platelets / Q000187:drug effects / Q000648:ultrastructure; D002448:Cell Adhesion / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D020099:Coated Materials, Biocompatible / Q000494:pharmacology*; D018922:HL-60 Cells; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology* / Q000187:drug effects; D006801:Humans; D008168:Lung / Q000187:drug effects*; D008567:Membranes, Artificial; D010100:Oxygen / Q000737:chemistry*; D010973:Platelet Adhesiveness / Q000187:drug effects; D011090:Polyenes / Q000737:chemistry; D060888:Real-Time Polymerase Chain Reaction; D013499:Surface Properties; D014025:Titanium / Q000494:pharmacology*
chemical_list: D020099:Coated Materials, Biocompatible; D008567:Membranes, Artificial; D011090:Polyenes; C009495:titanium dioxide; C087577:poly(4-methyl-1-pentene); D014025:Titanium; D010100:Oxygen
keywords: Endothelialization; Extracorporeal membrane oxygenation; Platelet adhesion assay; Pulsed vacuum cathodic arc plasma deposition; Titanium dioxide