Chitosan–PVA monodisperse millimeter-sized spheres prepared by electrospraying reduce the thromboembolic risk in hemorrhage control

Abstract

Uncontrolled hemorrhage is the main cause of death in many situations. Substantial efforts have been focused on developing more efficient hemostatic agents. Meanwhile, their safety is also critical for their application. Chitosan is an attractive natural polymer and has been widely investigated for hemostatic application. This study sought to incorporate poly(vinyl alcohol) (PVA) components and fabricate them into monodisperse millimeter-sized spheres to improve efficiency and safety. Chitosan–PVA spheres were fabricated by electrospraying and ionotropic gelation. The millimeter-sized spheres were obtained by adjusting the electrospraying parameters, including applied voltage, working distance, feed rate, polymer solution and component content. The morphology, chemical structure and thermostability of the spheres were characterized by variable pressure scanning electron microscopy (VP-SEM), Fourier transform infrared (FTIR) spectroscopy and thermogravimetric analysis (TGA). These spheres showed narrow size distribution and good biocompatibility. The hemostatic effect was evaluated both in vitro and in vivo using a blood coagulation timing experiment and a rat liver hemorrhaging model, and chitosan₅₀–PVA₅₀ spheres showed the best effect. PVA contributed to the high swelling degree of the spheres and the enhanced hemostatic effect. These spheres also significantly reduced thromboembolus formation in controlling femoral artery bleeding compared with chitosan powder, providing an efficient and safe hemostasis agent.