Endothelialized TiO <sub>2</sub>- and Ti45Nb-Coated PMP, PDMS and PES/PVP Membranes for Biohybrid Lung Support

Abstract

Lacking hemocompatibility of extracorporeal membrane oxygenation led to a biohybrid lung concept, in which gas exchange membranes are seeded with endothelial cells to form long-term stable surfaces. However, extensive surface modification of large oxygenator membranes is required for cell adhesion. In this study, polymethylpentene (PMP), polydimethylsiloxane (PDMS) and polyethersulfone/polyvinylpyrrolidone (PES/PVP) membranes were functionalized with thin films of titanium dioxide (TiO 2 ) or titanium-niobium (Ti45Nb), and characterized by field emission scanning electron microscopy, ellipsometry, X-ray photoelectron spectroscopy and gas permeability measurements. Endothelialized membranes were cultured under static conditions to evaluate cell coverage. Cell retention was investigated in a bioreactor system under flow conditions with a wall shear stress of 0.5 Pa, and cells were stained for endothelial markers CD31 and von Willebrand factor (vWf). Film thicknesses of 3.3±0.2 nm and 5.5±0.3 nm were determined for TiO2 and Ti45Nb coatings, respectively. With the exception of a slight decrease for PDMS+Ti45Nb, gas permeabilities of coated PMP and PDMS membranes did not deteriorate significantly compared to uncoated membranes. The microporous structure and the high hydrophilicity of PES/PVP prevented permeability measurements and subsequent dynamic culture due to membrane wetting. However, mean cell density increased substantially for all coated membranes compared to uncoated membranes. Although endothelialized PDMS+Ti45Nb showed minor cell layer defects, all coated PMP and PDMS membranes demonstrated integral cell layers after dynamic culture that stained positive for CD31 and vWf. This study has shown the suitability of thin TiO2 and Ti45Nb films for flow-stable endothelialization of gas exchange membranes for application in a biohybrid lung.