Effect of chitosan and carboxymethyl chitosan on fibrinogen structure and blood coagulation

Chitosan has numerous biomedical applications such as tissue engineering scaffolds, drug/gene delivery systems, hemostasis materials, antibacterial materials, wound dressing, etc. In any case, chitosan administered in vivo would positively or passively contact or enter blood tissue. In this situation, the interaction of chitosan with blood components is critical to determine the efficacy and safety of the polymer. In this study, the effect of chitosan with different molecular weight and its derivative carboxymethyl chitosan (CMC) on the structure and function of clotting-related proteins was studied. Specifically, the structural and conformational change of fibrinogen, an important clotting protein, was studied by using UV, fluorescence, and circular dichroism spectroscopy, respectively. Further, the impact of chitosan and CMC on the clotting function was evaluated with activated partial thromboplastin time (APTT), prothrombin time (PT), fibrinogen time (FT), and thromboelastography (TEG) assays. These results showed that, chitosan and fibrinogen can form complex mainly by electrostatic attraction. As a result, the structure and conformation of fibrinogen are altered by chitosan and CMC. Additionally, the presence of chitosan and CMC has little impact on the values of APTT, PT and FT, but causes significant abnormality in the clotting process by changing TEG parameters. These results provide important insight into the molecular basis for the biological response to chitosan and other biopolymers.