Synthesis of Heparin-Immobilized, Magnetically Addressable Cellulose Nanofibers for Biomedical Applications

Magnetically responsive heparin-immobilized cellulose nanofiber composites were synthesized by wet-wet electrospinning from a nonvolatile, room-temperature ionic liquid (RTIL), 1-methyl-3-methylimidazolium acetate ([EMIM][Ac]), into an aqueous coagulation bath. Superparamagnetic magnetite (Fe₃O₄) nanoparticles were incorporated into the fibers to enable the manipulation of both dry and wet nanofiber membranes with an external magnetic field. Three synthetic routes were developed to prepare three distinct types of nanocomposite fibers: cellulose-Fe₃O₄-heparin monofilament fibers, cellulose-Fe₃O₄-heparin core-shell fibers with heparin covalently immobilized on the fiber surface, and cellulose -Fe₃O₄ core-shell fibers with heparin physically immobilized on the fiber surface. These nanocomposite fibers were characterized by electron microscopy to confirm their coaxial structure and the fiber dimensions (fiber diameter 0.2-2.0 μm with 0.1-1.1 μm core diameter). Thermogravimetric analysis, liquid chromatography-mass spectrometry, Fourier transform infrared and X-ray diffraction spectroscopy provided detailed compositional analysis for these nanocomposite fibers, confirming the presence of each component and the surface accessibility of the heparin. The anticoagulant activity of immobilized heparin on the nanocomposite fiber surfaces was evaluated and confirmed by antifactor Xa and antifactor IIa assays.