Towards the development of a bioartificial lung - Endothelialisation of TiO coated oxygenator membranes

Currently, the use of extra corporeal membrane oxygenation (ECMO) devices, which is indicated for patients awaiting lung transplantation, is limited to a few weeks only, due to thrombus formation and deposition of blood components within the device. The aim of this project is to improve the haemocompatibility of ECMO devices by endothelialisation of the blood contacting surfaces. In order to achieve this, a coating technique is required to mediate the adhesion of endothelial cells (EC) to the hydrophobic polymers. The present study assesses the eligibility of titaniumdioxide (TiO 2 ), deposited onto poly-4-methyl-1-pentene gas exchange membranes (PMP), as a mediator of endothelialisation. PMP film samples (3x3cm) were coated with TiO 2 using the pulsed vacuum cathodic arc plasma deposition (PVCAPD) technique and analysed using SEM and EDX, which confirmed the homogeneous dispersion of nano-sized TiO 2 particles. ECs seeded onto the coated samples were able to adhere and generated a confluent monolayer. Real-time RT-PCR revealed that the seeded ECs retained the anti-thrombogenic, non-activated state, which was also confirmed using a leucocyte adhesion assay. Established EC monolayers demonstrated resistance to high physiologic flow shear stress (30 dyne/cm 2 ) for 24h and self-healing capacity. The TiO 2 coating was applied to PMP hollow fibres, which were subsequently seeded with ECs and demonstrated complete EC adhesion and coverage. This study demonstrated that TiO 2 coating via PVCAPD is a promising technique for coating thermo-sensitive PMP gas exchange membranes, enabling the generation of a non-activated and flow-resistant EC monolayer.