Use of Combinatorial Additives to Improve the Hemostatic Property of Chitosan Hydrogel

Abstract

Uncontrolled blood loss during traumatic, combat wounds and surgical procedures is a major challenge in modern medicine. Additional hemostatic techniques are required when the normal coagulation process is unable to function. The hemostatic techniques that are commonly used involve the use of mechanical, thermal and chemical agents. The use of mechanical agents in inaccessible areas is not possible and the use of thermal agents emit heat that could cause tissue necrosis. In certain conditions, chemical agents in the form of topical hemostatic agents facilitate control of excessive blood loss. Chitosan has widespread application in clinics as a topical hemostatic agent. Chitosan based hemostatic agents interact electrostatically with components of blood and seal the injury site. The FDA approved chitosan based topical hemostatic agents (sponge, dressing, and granules) require compression at the injury site to control blood loss. Hemostatic agent in the form of an injectable hydrogel would have the ability to completely fill irregularly shaped wounds and control bleeding effectively. The hemostatic property of chitosan could be enhanced by incorporation of inorganic additives such as potassium aluminium sulfate and calcium chloride. Potassium aluminium sulfate is an astringent that would precipitate proteins at the tissue surface and cause vasoconstriction. Calcium ions are essential for the activation of coagulation factors that lead to stable fibrin mesh formation at the injured site. The combinatorial effect of the additives would aid in rapid bleeding control by acting simultaneously on the mechanisms (hemostatic plug formation, vasoconstriction, and activation of coagulation cascade) involved in hemostasis. Therefore, this work focuses on studying the mechanism of action of each component present in the hydrogel and further evaluating the hemostatic efficacy and toxicological response of the prepared composite hydrogel applied on the hemostatic model of liver and femoral artery in the animal model..