Blood-aggregating hydrogel particles for use as a hemostatic agent

Abstract

The body is unable to control massive blood loss without treatment. Available hemostatic agents are often expensive, ineffective or raise safety concerns. Synthetic hydrogel particles are an inexpensive and promising alternative. In this study we synthesized and characterized N-(3-aminopropyl)methacrylamide (APM) hydrogel particles and investigated their use as a hemostatic material. The APM hydrogel particles were synthesized via inverse suspension polymerization with a narrow size distribution and rapid swelling behavior. In vitro coagulation studies showed hydrogel particle blood aggregate formation as well as bulk blood coagulation inhibition. In vivo studies using multiple rat injury and ovine liver laceration models demonstrated the particles’ ability to aid in rapid hemostasis. Subsequent hematoxylin and eosin and Carstairs’ method staining of the ovine liver incision sites showed significant hemostatic plug formation. This study suggests that these cationic hydrogel particles form a physical barrier to blood loss by forming aggregates, while causing a general decrease in coagulation activity in the bulk. The formation of a rapid sealant through aggregation and the promotion of local hemostasis through electrostatic interactions are coupled with a decrease in overall coagulation activity. These interactions require the interplay of a variety of mechanisms stemming from a simple synthetic platform.