Abstract
We have developed new membrane systems for biohybrid liver and kidney support providing both blood and tissue compatibility. This was achieved by a tailored composition of acrylonitrile copolymers (i), the surface modification of membranes based on poly(etherimide) creating bi-functional membranes (ii), or the application of a specific hollow fibre design with an outer membrane surface for blood and an inner surface for tissue contact or vice versa (iii). The optimisation of polymer composition with regard to blood and tissue compatibility can be obtained using N-vinylpyrrolidone as co-monomer during polymer synthesis. Membranes made of these copolymers have an increased hydrophilicity, improved blood compatibility and support functional activity of kidney epithelial (MDCK) and human hepatoblastoma cells. Another option is the modification of membrane surface with blood or tissue compatible ligands, Here, it is shown that the covalent binding of heparin improves the blood response of amine-functionalisied membrane materials. A further approach is the combination of blood and tissue compatible membrane materials in a specific bioreactor with a fibre-in-fibre design or the preparation of bilayer membranes with a novel technique composed of two different polymer materials that can be blood or tissue compatible. It was possible to cultivate kidney epithelial cells in the inter-fibre-space in such a way that cells built up a monolayer with the features of a normal epithelium while no contact was made to the blood compatible membrane surface. In summary, a number of techniques are available to tailor membrane systems for application in biohybrid organs.