Molecularly-imprinted hydrogel beads via self-sacrificing micro-reactors as safe and selective bilirubin adsorbents

Abstract

For patients who are suffering from liver dysfunction or metabolic obstruction, excessive bilirubin (BIL) in their bodies may cause jaundice with irreversible cerebral injury. Traditional exchange transfusion and photodynamic therapy pose a risk of serious adverse reactions or limited curative effects. Therefore, as a generally used treatment, hemoperfusion (HP) purifies patients’ blood with solid adsorbents. However, the development of clinical BIL absorbents is greatly impeded by low selectivity and unsatisfactory blood compatibility. Herein, inspired by oviparity, we propose BIL-imprinted poly(acrylic acid-co-sodium p-styrenesulfonate)–reduced graphene oxide (PAA–SS–rGO@BIL) hydrogel beads as BIL adsorbents via self-sacrificing micro-reactors. In the micro-reactors, cross-linked polymerization is achieved and a solidified gel is formed. The received hydrogel beads show outstanding selective adsorption capabilities toward BIL due to the recognition sites, and π–π and hydrophobic interactions. Such hydrogel beads possess superior blood compatibility owing to their bioinspired heparin-mimicking gel structure. Simulated BIL selective adsorption experiments in vitro demonstrate that the BIL concentrations in the plasma of a patient with severe jaundice can be restored to a moderate level within 3 hours. Therefore, hydrogel beads offer new options for clinical BIL adsorption.