Layered Double Hydroxide: A New Ceramic‐Based Hemostatic Agent?

Abstract

Layered double hydroxides (LDHs), well known as anionic clays or hydrotalcite-like compounds consist of positively charged layers. Net positive charges on the layers are balanced by exchangeable anions along with water molecules in the interlayer space. In the present research, the potential for use of Ca/Al-LDH as local hemostatic agent is evaluated in vitro by measuring the coagulation time of human fresh blood in the presence of LDH powder. Crystalline Ca/Al-LDH powders required for these experiments were synthesized via a co-precipitation method followed by a controlled hydrothermal process using calcium nitrate and aluminum nitrate as starting materials under certain synthetic conditions such as time and concentration. XRD and SEM analyses were utilized to characterize the synthetic powders. XRD and SEM results demonstrate the presence of a crystalline pure Ca/Al-LDH with hexagonal morphology. In order to investigate the biocompatibility of the samples, culture techniques were employed using mouse fibroblast cells (L929) as reference cell line. The results reveal that LDH powder can accelerate the platelet aggregation and the formation of blood clot. Moreover, the samples show good cell proliferation and high cell viability to L929 cell line compared with negative control sample. These results demonstrate that these layered materials are suitable candidates for using as local hemostatic agent to hemorrhage control and can reduce blood loss in lethal injuries. INTRODUCTION Uncontrolled bleeding and consequent hemorrhagic shock are leading causes of death in many injuries and early hemorrhage control can improve outcome [1-2]. In minor accidents, the bleeding may be controlled by the body's own blood clotting mechanisms. But in more severe wounds, additional controls such as applying pressure or using of absorbent dressings or pads are required. But these methods may be ineffective for severe bleedings or bleedings in persons with lessened blood clotting mechanisms. One efficient way to control bleeding is to use a hemostatic agent in the form of powder, foam, pad, etc. at the source of the bleeding. Limited materials are known for hemorrhage control [3]. Such an agent must be safe, rapidly effective and have good systemic and local compatibility [4]. Several fibrin-based, collagen-based, cellulose-based and gelatin-based [4-7] systems are been introduced as local hemostatic agents. While these materials are effective for control of bleeding, they are expensive. A newer local hemostatic agent –commercially named QuikClot ® is a zeolite-based powder that shows good control in many bleedings with different bleeding sources [1-2, 8-9]. Zeolites are a family of Silicates that are one of the most abundant classes of minerals on Earth. Clays are a group of inorganic materials that have structural similarities to zeolites [10]. Layered Double Hydroxides (LDHs), also called anionic clays or hydrotalcite-like compounds, are clay-like materials that show promising properties for a large number of applications. Layered double hydroxides (LDHs) have been known for over 150 years since the discovery of the mineral hydrotalcite. They are a broad class of inorganic lamellar compounds with high capacity for anion intercalation. The LDH structure -represented by [M 2+ 1-xM 3+ x(OH)2] x+ (A n)x/n·mH2Oresults from the stacking of brucite-like layers ([Mg(OH)2]) containing extra positive charge due to the partial isomorphous substitution of M 2+ by M 3+ . This positive excess charge is balanced by anions, which exist in the interlamellar spaces [1-3]. Layered double hydroxides display unique physical and Page 1 of 5