Calcium Ion-Coupled Polyphosphates with Different Degrees of Polymerization for Bleeding Control.

ABSTRACT

The development of efficient hemostatic materials is crucial for achieving rapid hemorrhage control and effective wound healing. Inorganic polyphosphate (polyP) is recognized as an effective modulator of the blood coagulation process. However, the specific effect of polyP chain length on coagulation is not yet fully understood. Furthermore, calcium ions (Ca2+) are essential for the coagulation process, promoting multiple enzyme-catalyzed reactions within the coagulation cascade. Hence, calcium ion-coupled polyphosphate powders with three different degrees of polymerization (CaPP-n, n = 20, 50, and 1500) are synthesized by an ion-exchange reaction. CaPP exhibits a crystalline phase at a low polymerization degree and transitions to an amorphous phase as the polymerization degree increases. Notably, the addition of Ca2+ enhances the wettability of polyP, and CaPP promotes hemostasis, with varying degrees of effectiveness related to chain length. CaPP-50 exhibits the most promising hemostatic performance, with the lowest blood clotting index (BCI, 12.1 ± 0.7%) and the shortest clotting time (302.0 ± 10.5 s). By combining Ca2+ with polyP of medium-chain length, CaPP-50 demonstrates an enhanced ability to accelerate the adhesion and activation of blood cells, initiate the intrinsic coagulation cascade, and form a stable blood clot, outperforming both CaPP-20 and CaPP-1500. The hemostatic efficacy of CaPP-50 is further validated using rat liver bleeding and femoral artery puncture models. CaPP-50 is proven to possess hemostatic properties comparable to those of commercial calcium-based zeolite hemostatic powder and superior to kaolin. In addition, CaPP-50 exhibits excellent biocompatibility and long-term storage stability. These results suggest that CaPP-50 has significant clinical and commercial potential as an active inorganic hemostatic agent for rapid control of bleeding.