Novel Surface Functionalized Polymers with Tailored Porosity for Cytokine Removal

Extracorporeal blood purification techniques represent a therapeutic approach to clinically support patients suffering from specific pathological conditions. These systems aim at the removal or at the modulation of molecules responsible for the disease state. The treatment may be performed by circulating whole blood (hemapheresis) or plasma (plasmapheresis) in membrane-adsorption systems. The depletion of the target molecules is based on physical adsorption, chemisorption, or ion exchange. Cytokines are potential targets for adsorption in conditions associated with systematic inflammation, such as sepsis and septic shock. The aim of this project is to create a universal blood-compatible carrier to be used as basic matrix in hemosorption. Particularly, this project focuses on the development, characterization and optimisation of (1) novel porous poly(styrene-co-divinylbenzene-co-vinylbenzyl chloride) (PS/DVB/VBC) hypercrosslinked beads and (2) tris(hydroxymethyl)aminomethane (Tris) derivatized (PS/DVB/VBC-Tris) beads with hydrophilic surface prepared by suspension polymerisation for application in extracorporeal cytokine removal. The innovative aspect of this project is the particular attention paid to the mechanism by which adsorbent properties may induce thrombocyte activation and adhesion as well as release of extracellular vesicles from activated blood cells. Therefore, we will not only focus on the cytokine removal, but also on indicators of hemocompatibility, such as endothelial activation, hematological parameters, thrombocyte activation/adhesion and release of extracellular vesicles. In conclusion, this study will give an overview about cytokine adsorption capacity and hemocompatibility of the newly developed PS/DVB/VBC based adsorbents. The results acquired in this project will allow us to correlate the physiochemical parameters to cytokine adsorption capacity and blood compatibility of the PS/DVB/VBC based polymers for extracorporeal cytokine adsorption. The project will be divided into 4 work packages: 1) PS/DVB/VBC beads preparation and characterization (lead partner UM); 2) PS/DVB/VBC-Tris beads preparation and characterization (lead partner UM); 3) Characterisation of Adsorbents for Cytokine Removal from Plasma and Whole Blood (DUK); 4) Evaluation of Hemocompatibility of PS/DVB/VBC-Tris beads with hydrophilic surface (DUK).