Membrane concepts for blood purification : towards improved artificial kidney devices

Abstract

The research presented in this thesis is about the fabrication and characterization of new membranes for blood purification. A novel membrane concept is proposed to combine diffusion and adsorption in one step to remove uremic retention solutes. A membrane with embedded functionalized particles, a so called mixed matrix membrane (MMM) is developed for this. This concept might improve uremic toxin removal and it is an interesting strategy for application in a wearable artificial kidney since two techniques can be combined in one step. Dual layer MMMs with activated carbon particles embedded in the membrane matrix with a particle free membrane layer on the blood contacting side to improve hemocompatibility and prevent release of particles are developed, in both flat sheet and hollow fiber configuration. The developed dual layer MMMs have high clean water permeance and adsorb various uremic retention solutes and also the protein-bound toxins p-cresylsulfate, indoxyl sulfate and hippuric acid from spiked human plasma. We show that MMMs can combine diffusion and adsorption of a uremic retention solute in one step and the MMMs show great potential for clearance of difficult to remove protein-bound toxins. In addition, various adsorptive particles are investigated for adsorption of several categories of uremic toxins and show potential for incorporation into a MMM. Furthermore, membranes are developed using a the new material SlipSkinTM which is a copolymer made from N-vinylpyrrolidone (NVP) and butylmethacrylate (BMA). Membrane morphology is dependent on several fabrication parameters and these membranes show low platelet adhesion and equivalently good properties of contact activation, thrombogenicity, leukocyte adhesion, hemolysis, complement activation compared to membranes used in the clinic and other benchmark membranes. Overall, this thesis presents results on various membrane developments towards improved blood purification. Further research could stimulate the application of the mixed matrix membranes either for improvement of the current hemodialysis or apheresis therapies or as an integral part of a wearable artificial kidney.