TY - JOUR

T1 - Endothelialization and characterization of titanium dioxide-coated gas-exchange membranes for application in the bioartificial lung

AU - Pflaum, Michael

AU - Kühn-Kauffeldt, Marina

AU - Schmeckebier, Sabrina

AU - Dipresa, Daniele

AU - Chauhan, Kanchan

AU - Wiegmann, Bettina

AU - Haug, Rolf J.

AU - Schein, Jochen

AU - Haverich, Axel

AU - Korossis, Sotirios

N1 - Funding information: The authors would like to acknowledge the contribution of Dr. Tetyana Melnyk at the Laser Center Hannover e.V., and the Hannover Medical School SEM core facility for their support with the SEM and EDX analysis. The authors would also like to acknowledge the support of Dr. Amer Hakki in the contact angle measurements and Jennifer Wolf for the technical assistance in the lab. This study was financially supported by the Cluster of Excellence REBIRTH (From Regenerative Biology to Reconstructive Therapy EXC 62, Unit 4.1), the German Centre for Lung Research (DZL) BREATH (Biomedical Research In Endstage And Obstructive Lung Disease Hannover) (DZL: 82DZL00201), and the German Research Foundation (DFG) (WI 4088/1-2).

PY - 2017/3/1

Y1 - 2017/3/1

N2 - 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 TiO2 coating 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 TiO2 coating mediated EC attachment and the establishment of a functional EC monolayer. Statement of Significance 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.

AB - 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 TiO2 coating 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 TiO2 coating mediated EC attachment and the establishment of a functional EC monolayer. Statement of Significance 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.

KW - Endothelialization

KW - Extracorporeal membrane oxygenation

KW - Platelet adhesion assay

KW - Pulsed vacuum cathodic arc plasma deposition

KW - Titanium dioxide

UR - http://www.scopus.com/inward/record.url?scp=85008213590&partnerID=8YFLogxK

U2 - 10.1016/j.actbio.2016.12.017

DO - 10.1016/j.actbio.2016.12.017

M3 - Article

C2 - 27956361

AN - SCOPUS:85008213590

VL - 50

SP - 510

EP - 521

JO - Acta biomaterialia

JF - Acta biomaterialia

SN - 1742-7061

ER -