Moderately Hydrophilic Gigaporous Polystyrene@ZIF-8 Composite Microspheres for Synergy-Enhanced Removal of Bilirubin

Abstract Commercial hemoperfusion adsorbents for hyperbilirubinemia are mainly polystyrene (PS) anion exchange resins due to their high mechanical strength, satisfactory physicochemical stability, and low cost, enabling bilirubin removal via electrostatic interactions. However, these resins pose two major issues in clinical use: heparin binding and coagulation activation. In this work, we developed moderately hydrophilic gigaporous polystyrene (mHGPS) microspheres with a surface that balances hemocompatibility and hydrophobic bilirubin adsorption, and then immobilized ZIF-8 in situ to obtain mHGPS@ZIF-8 composite microspheres for synergy-enhanced selective bilirubin adsorption. The composite microspheres were featured with through-connected gigapores (∼1.05 μm), high porosity (64.02%), high permeability (7.31 × 10–11 m2) and satisfactory hemocompatibility with a hemolysis rate of 1.67%. Compared to mHGPS microspheres, the mHGPS@ZIF-8 composite microspheres exhibited a 2.6-fold increase in the adsorption capacity for bilirubin (from 53.1 mg/g to 138.9 mg/g). Notably, an even greater 3.1-fold enhancement was achieved for albumin-bound bilirubin (from 18.7 mg/g to 57.8 mg/g). Moreover, benefiting from the gigaporous structure of mHGPS microspheres, mHGPS@ZIF-8 composite microspheres exhibited rapid bilirubin removal kinetics, removing 89.0% of bilirubin within 60 min during simulated hemoperfusion, with minimal albumin loss (1.2%). This work establishes a strategy for designing high-performance bilirubin adsorbents with significant potential for treating hyperbilirubinemia.