Design of carboxymethyl chitosan-based heparin-mimicking cross-linked beads for safe and efficient blood purification

Abstract

Safe and efficient carboxymethyl chitosan (CMC)-based heparin-mimicking cross-linked beads (CMC/PAMPS) as adsorbents for the clearance of low-density lipoprotein-cholesterol (LDL-c) in blood purification were prepared through hydrogen bonding interactions followed with in situ cross-linking with 2-acrylamido-2-methyl-1-propanesulfonicacid (AMPS). Fourier transform infrared spectra (FTIR), two-dimensional correlation FTIR spectroscopy (2D IR), thermal gravimetric analysis (TGA) and energy dispersive X-ray spectrometer (EDS) demonstrated the successful synthesis of CMC/PAMPS beads. The porous structures of the beads may contribute to the adsorption of toxins. Owing to their favorable hydrophilicity, when contacted with blood, the beads showed excellent hemocompatibility. The hemolysis ratios for all the beads were less than 5%, the thromboplastin time of CMC/PAMPS10 beads exceed 600 s, and they can suppress contact activation and complement activation effectively. Additionally, the beads have no obvious cytotoxicity with endothelial cells, thus could be used as a safe adsorbent for blood purification. Moreover, the CMC/PAMPS10 beads possessed a LDL-c adsorption capacity of 24.8 mg/g under static adsorption and a LDL-c adsorption capacity of 8.2 mg/g in the simulation of hemoperfusion for whole blood, due to the large surface areas and high density of functional groups. Meanwhile, the concentration of high-density lipoprotein-cholesterol (HDL-c) was almost unaffected. In general, the safe adsorbent with high LDL-c adsorption capacity has great potentials for hemoperfusion and other clinical applications.