Freezing-induced chemical crosslinking to fabricate nanocellulose-based cryogels for efficient bilirubin removal

Abstract

Construction of robust polysaccharide-based cryogels that can efficiently adsorb bilirubin is of great significance in blood purification field. However, the crosslinking of polysaccharides usually occurs before the formation of enough large ice crystals, which leads to the weak mechanical strength and relatively small pores. Herein, a novel approach is presented to fabricate microfibrillated cellulose (MFC) cryogels by using freezing-induced Michael addition reaction at −12 °C. Due to the extrusion by ice crystals and cryo-concentrated pH increase during the cryogelation process, the chemical crosslinking between bis(vinylsulphonyl)methane (BVSM) cross-linker and close contact MFCs was activated. The obtained MFC cryogels exhibit excellent mechanical strength and outstanding chemical stability under harsh conditions. Subsequently, the MFC cryogels were decorated with polyethyleneimine (PEI), bestowing them with the capability of adsorbing bilirubin. Furthermore, the biocompatibility of the resulting PEI-MFC cryogel was investigated by acute hemolysis test, MTT assay, blood coagulation experiment, along with the adhesion experiment of platelets and red blood cells, demonstrating good cytocompatibility and hemocompatibility. Finally, the adsorption performances of PEI-MFC cryogels for bilirubin in PBS and biological solution were evaluated. The PEI-MFC cryogel can efficiently adsorb bilirubin from 40.0 g L−1 bovine serum albumin solution, with a record-high adsorption capacity of 351.49 mg g−1. More importantly, the PEI-MFC cryogel could also maintain high dynamic adsorption efficiency in self-made hemoperfusion devices. This facile approach provides a new avenue to develop cellulose-based high-performance hemoperfusion adsorbent for the removal of bilirubin, showing a great promise for the translational therapy of hyperbilirubinemia.