Advanced polyelectrolyte complexes for ultrafast hemostasis and blood superabsorption

Abstract

Blood clotting is the natural response of the human body to hemorrhage - one of the leading causes of death worldwide. Hemostatic sponges are used to physically block the bleeding site, reduce blood clotting time, and increase the chance of survival post injury. In this study, tuning electrostatic interactions in a polyelectrolyte complex resulted in a superabsorbent hemostatic device capable of time-controlled release of procoagulant polyphosphates (PP). Sponge scaffolds made of modified chitosan with a controlled number of negatively- and positively- charged functional groups were used as the PP carrier, enabling controlled release of PP through competing electrostatic interactions. The binding of PP to the modified chitosan and its release were studied mechanistically at the molecular scale, while the blood clotting capability of the sponges was assessed quantitatively under static and dynamic conditions in vitro, and using a rat hepatic hemorrhage model in vivo. Consistent results between the in vitro and in vivo experiments indicated that the hemostatic sponges can decrease the blood clotting time by up to 75 % while absorbing fluid up to 25 times their dry mass within an 8 h period after exposure to the blood, making them suitable for various bleeding conditions. STATEMENT OF SIGNIFICANCE: Improving the chance of survival following trauma bleeding depends on fast and effective blood control. The efficacy of polyphosphates in accelerating the natural blood clotting has been known for over two decades. However, polyphosphates could not be used for accelerated external blood clotting due to the narrow range of its effective concentration. This article shows that controlling competing electrostatic interactions in a polyelectrolyte complex containing polyphosphates is an effective strategy to maintain the effective concentration of polyphosphates at the external bleeding site to maximize its blood clotting efficacy. With comprehensive ex vivo, microfluidic and in vivo analyses, the efficacy of the polyelectrolyte complex in controlling the blood clotting rate while absorbing a significant volume of blood is demonstrated.

Keywords: Bleeding; Chitosan; Controlled release; Electrostatics; Hemostasis; Polyphosphate.