Simultaneous hypercrosslinking and functionalization of porous polystyrene adsorbent for protein-bound uraemic toxins removal

Protein-bound uremic toxins (PBUTs) play a crucial role in the progression of uremic complications. Due to the extremely high binding affinity to human serum albumin, PBUTs are poorly removed by traditional hemodialysis methods. As an advanced blood purification technology, hemoperfusion has been proven effective in removing PBUTs, and hyper-crosslinked polystyrene adsorbents have been widely commercialized as hemoperfusion adsorption materials. However, challenges still remain, including the need to enhance the adsorption efficiency of PBUTs and the simplification of the preparation and modification processes of the adsorbents. In this work, we report a one-step external crosslinking modification technique to prepare a functionalized hyper-crosslinked polystyrene adsorbent named HCP-DFDA, in which N,N-dimethylformamide dimethyl acetal (DFDA) with tertiary amine functional groups was used as a small-molecule external crosslinker to simultaneously carry out Friedel–Crafts alkylation crosslinking and functional group grafting modification. Experimental results showed that the prepared hypercrosslinked resin HCP-DFDA had abundant mesoporous/microporous structures and an extremely high specific surface area of up to 1030 m²/g. Adsorption experiments demonstrated that HCP-DFDA exhibited excellent adsorption performance for both uremic PBUTs like indoxyl sulfate (IS) and p-cresyl sulfate (PCS) and medium- to large-molecular-weight toxins such as β2-microglobulin (β2-MG) and interleukin-6 (IL-6). Moreover, similar to the commercial HA130 resin, HCP-DFDA exhibited low protein adsorption and hemolysis rates, demonstrating good blood compatibility. In summary, the facile preparation method of the modified hypercrosslinked adsorbent proposed in this study provides a new idea and solution for the efficient removal of PBUTs through whole-blood hemoperfusion in clinical applications.