Modified porous carboxymethyl chitin microspheres by an organic solvent-free process for rapid hemostasis

Carbohydr Polym. 2021 Oct 15:270:118348. doi: 10.1016/j.carbpol.2021.118348. Epub 2021 Jun 17.

Abstract

Rapid and effective hemorrhage control is essential to reduce mortality following traumatic injuries. Herein we developed an organic solvent-free process to prepare carboxymethyl chitin microsphere (CMCHm) in an aqueous two-phase system through heating and freeze-drying. To further enhance the hemostatic performance of CMCHm, we loaded calcium ions and in-situ polymerized dopamine to get modified hemostatic microspheres CMCHm-Ca2+ and CMCHm-PDA, respectively. The size of these microspheres was mainly distributed between 50 μm and 150 μm, and the porous microstructure was observed by SEM. The data of in vitro degradation, cell cytotoxicity, and hemolysis test indicated good biocompatibility of these microspheres. Importantly, CMCHm-Ca2+ and CMCHm-PDA displayed better hemostatic performance compared with CMCHm and the positive controls Yunnan baiyao® and Quickclean®. Especially, the bleeding time was reduced to 59 s (CMCHm-Ca2+) and 45 s (CMCHm-PDA) in the femoral artery/vein cut model, respectively. All these demonstrate CMCHm-Ca2+ and CMCHm-PDA hold great potential for rapid hemostasis.

Keywords: Aqueous two-phase system; Calcium ions; Carboxymethyl chitin; Hemostatic microsphere; Polydopamine.

MeSH terms

  • Animals
  • Blood Coagulation / drug effects
  • Cell Line
  • Chitin / analogs & derivatives*
  • Chitin / chemistry
  • Chitin / pharmacology
  • Dopamine / chemistry
  • Dopamine / pharmacology
  • Hemorrhage / drug therapy*
  • Hemorrhage / metabolism
  • Hemostasis / drug effects*
  • Hemostatics / chemistry*
  • Hemostatics / pharmacology
  • Mice
  • Microspheres*
  • Porosity
  • Rats
  • Solvents / chemistry

Substances

  • Hemostatics
  • Solvents
  • Chitin
  • O-(carboxymethyl)chitin
  • Dopamine