Abstract

Despite the widespread use of hypercrosslinked polystyrene (HCP) adsorbents in uremic blood purification, several challenges remain in improving their removal efficiency for both medium- to large-molecular-weight toxins (MLMTs) and protein-bound uremic toxins (PBUTs), as well as in simplifying the fabrication process. Here, we report a facile Friedel–Crafts approach for the synthesis of amino-functionalized hypercrosslinked polystyrene (HCP-AA) adsorbents. By employing amino-containing small-molecule crosslinkers, such as, 2,2-dimethoxyethanamine (DAA), we achieve simultaneous Friedel–Crafts alkylation and amine-group grafting onto pre-crosslinked polystyrene resins. This process allows for the tuning of microstructure and pore architecture through control of key parameters, including crosslinking degree and porogen composition. The resulting HCP-AA exhibits hierarchical porosity and abundant amino groups, leading to high adsorption capacities for a wide range of uremic toxins, including protein-bound toxins such as p-cresyl sulfate (PCS), and middle-to-large molecular weight toxins like β2-microglobulin (β2-MG) and interleukin-6 (IL-6). Importantly, HCP-AA demonstrates excellent blood compatibility, with hemolysis rates below 0.5% and minimal platelet activation, comparable to those of commercial resins. This scalable and cost-effective synthetic strategy provides a promising platform for the development of next-generation broad-spectrum uremic toxin adsorbents with dual functionalities, thereby advancing blood purification strategies for the treatment of kidney failure. Graphical abstract