Tannic acid-crosslinked gelatin composite microspheres adsorbed with CQAS or Ca2+ for rapid hemostasis

Abstract

In the case of massive blood loss due to natural disasters and wars, timely and rapid hemostasis is of great significance to improve the survival rate of injured people. Nevertheless, uncontrolled, noncompressible, and irregular bleeding wounds remain a giant challenge for rapid hemostasis. In this study, the tannic acid-crosslinked gelatin was first obtained by Michael addition reaction, and then the tannic acid-crosslinked gelatin composite microspheres (TGMs) were prepared by the emulsion cross-linking method. TGMs could significantly improve the water absorption and hemostatic performance compared with single component gelatin microspheres (GMs). Increasing the water absorption ratio and introducing blood coagulation factors into composite materials are simple and effective strategies to enhance the hemostatic properties. Therefore, chitosan quaternary ammonium salt (CQAS) and Ca2+ were electrostatic adsorbed to obtain two kinds of functional TGMs, which were respectively CQAS-absorbed TGMs (T2GMs-CQAS) and calcium ion-absorbed TGMs (T2GMs-Ca2+). Notably, T2GMs-CQAS, and T2GMs-Ca2+ could absorb water rapidly within 3seconds, in addition, especially the water absorption ratio of T2GMs-CQAS could reach 2.95 times compared with GMs. Benefited from rapid water absorption, coagulation pathway activation, and red blood cells aggregation of T2GMs-CQAS and T2GMs-Ca2+, resulting in rapid blood coagulation in vitro. In addition, CQAS and Ca2+ provided strong and intrinsic antibacterial activity due to positive charge. Moreover, in the tail amputation and liver hemostatic models, T2GMs-CQAS and T2GMs-Ca2+ demonstrated superior hemostatic effects compared to commercial Yunnan Baiyao®. In conclusion, T2GMs-CQAS and T2GMs-Ca2+ have potential applications as hemostatic dressings in uncontrolled, noncompressible, and irregular bleeding wounds.