One-step engineering dual-network reinforced hydrogel microspheres with excellent anti-coagulant and low-density lipoprotein removal

Abstract

Low-density lipoprotein apheresis (LDL-a) is a potent therapeutic strategy for treating hyperlipidemia and preventing atherosclerotic cardiovascular disease. However, the use of water-soluble anticoagulant during LDL-a treatment increases the risk of severe bleeding. In this study, dual-network composite polyacrylonitrile (PAN) hydrogel microspheres (CAHMs) are prepared through a one-step synthesis method using PAN, acrylic acid (AA) and 2-acrylamido-2-methyl-1-propanesulfonic acid (AMPS) as raw materials. Benefiting from the presence of PAN network, the CAHMs exhibit an average compressive stress of 7.16 MPa. Then, the hydrophilic network established by AA and AMPS leads to excellent LDL adsorption capacity and self-anticoagulant property, significantly inhibiting the activity of the blood coagulation factors VIII, IX, XI and XII, and prolonging the activated partial thromboplastin time (APTT) by fourfold. Moreover, according to the Sips model, the CAHMs exhibit a maximum static LDL adsorption capacity of 49.37 mg/g. In dynamic simulated perfusion experiments, the CAHMs achieve a total LDL adsorption capacity of 69.59 mg/g, 20 times higher than the adsorption capacity for HDL. The one-step synthesis method employed in this study guarantees rapid and large-scale production of the composite microspheres, which possess excellent mechanical strength, blood compatibility, self-anticoagulant property and LDL adsorption capacity. This one-step synthesis method has the advantage of abandoning organic solvent and stabilizer, thus provides a new idea for the industrial preparation of LDL absorbent used in whole blood.