Unusual surface coagulation activation patterns of crystalline and amorphous silicate-based biominerals

Activation of coagulation cascades, especially FX and prothrombin, prevents blood loss and reduces mortality from hemorrhagic shock. Inorganic salts are effective but cannot stop bleeding completely in large hemorrhagic events, and rebleeding carries a significant mortality risk. The coagulation mechanism of inorganic salts has been oversimplified in the past two decades, limiting the creation of novel hemostats. Here, on the interface the activation of the coagulation, fibrinolysis, and cell activities were monitored at the protein level. The link between the hydrophilic-hydrophobic interface, hydration layer, microenvironmental structure of the crystal and amorphous salt, protease activity, and adsorption was also uncovered. It reveals that strong water binding and fibrinogen adsorption on kaolin's surface causes rebleeding after hemostasis, resulting in a weak thrombus. The kaolin surface inhibited the FIXa and FVIIIa composite assembly, reducing its positive feedback on the extrinsic pathway. Inspiringly, amorphous bioactive glass (BG) with transient-dynamic ions microenvironment interface are designed to bypass the barrier of the crystal structure hydration shell, hence enhancing the continuous activation of the biomaterial surface on coagulation system. Under comparative exploration, the unique coagulation pattern of BG was obtained: upon contact with the hydrophilic BGs, intrinsic and extrinsic coagulation pathways continuously initiated under the dynamic ionic microenvironment, and prothrombin complexes successfully hydrolyzed to thrombin without platelet membrane involvement, speeding the production of high-strength clots. Further evidence proves that BG more than doubled the survival rate of SD rats than kaolin in the lethal femoral artery, vein, and nerve disconnection hemorrhage model. This study investigates how the surface of inorganic salts assists in coagulation cascades that may help elucidate the clinical application of kaolin-gauze and pave the way to new materials for managing hemorrhage.