Biosynthetic calcium-doped biosilica with multiple hemostatic properties for hemorrhage control

In this study, we reported calcium-doped biosilica (Ca-biosilica) with multiple hemostatic properties derived from Coscinodiscus sp. frustule. The incorporation of calcium into the diatom frustule was achieved by a simple biosynthetic route through feeding the diatoms with calcium chloride, which was confirmed by calcein staining and EDXS. Ca-Biosilica exhibited an efficient water absorption ratio (36.36 ± 1.44 times its own weight of liquid), superior compatibility (hemolysis ratio <5%, no cytotoxicity against MEFs) and excellent hemostatic effect (203.67 ± 15.63 s at 5 mg mL^-1; 145.01 ± 20.41 s at 10 mg mL^-1). The intrinsic blood coagulation pathway was clearly strengthened by the unique interface of Ca-biosilica, which was rich in silanol groups and calcium, leading to fast hemorrhage control in rat-tail amputation model. The clotting time of Ca-biosilica was 88.34 ± 28.54 s, which was similar to that of Quickclot® zeolite, whereas only one-third blood loss by weight (0.21 ± 0.16 g) was found in Ca-biosilica-treated group compared with that of the Quickclot® zeolite group (0.63 ± 0.09 g). The results prove that Ca-biosilica is promising as a quick hemostatic agent due to its effectiveness, excellent biocompatibility and simple and environmentally friendly preparation process.