Graphene-kaolin composite sponge for rapid and riskless hemostasis

Highlights

• GKCS rapidly stops bleeding in approximately 73 s in rabbit artery injury test.

• Hemolysis and cytotoxicity assays demonstrate GKCS’ biocompatibility.

• Synergic mechanism on bleeding control is discussed.

• It is a facile and efficient method to make a hemostatic composite.

• GKCS is a new Kaolin-based or graphene-based hemostasis.

Abstract

Kaolin is an effective and safe hemostatic agent for hemostasis. However, its ontic powder is difficult to use in actual practice. To develop a wieldy and powerful hemostat, composite strategy is usually a good choice. Herein, we developed a graphene-kaolin composite sponge (GKCS), synthesized with graphene oxide sheets, linker molecules and kaolin powders through a facile hydrothermal reaction. SEM observations support that GKCS has a porous structure, and EDS mapping further confirms that kaolin powders are embedded in graphene sheets. Once GKCS is exposed to bleeding, plasma is quickly absorbed inside the sponge, meanwhile blood cells are gathered at the interface. The gathered blood cells are in favor of accelerating clotting due to multi stimulations, including concentration, surface charge and activation of hemostatic factors, originating from both kaolin powders and graphene sponge. As a result, GKCS could stop bleeding in approximately 73 s in rabbit artery injury test. Besides, cytotoxicity and hemolysis assessments highlight that GKCS has a good biocompatibility. These remarkable properties suggest that GKCS is a potential riskless hemostatic agent for trauma treatment.

Introduction

Hemorrhage is the leading cause of death in emergency and intraoperative bleeding, which results in complications such as hemorrhagic shock, infection, and organ failures [[1], [2], [3]]. Excessive bleeding causes nearly 40% of deaths and is the main reason of traumatic death [4,5]. Therefore, using safe and efficient hemostatic materials are important to save life. Up to now, many kinds of hemostatic materials have been developed, such as zeolite [6], porous silica [7], granulose [8] and chitosan [9]. For inorganic micro- or meso-porous materials, they promote hemostasis on the base of fast liquid absorption and the enrichment of bloods cells and platelets [[10], [11], [12], [13]]. While organic glyco-based materials prefer to gather red blood cells to accelerate blood clotting by electrostatic interaction and gelation. However, most of those hemostats tend to entrap themselves in scab when exerting their performance, which will weaken hemostatic efficiency and cause unnecessary discomfort.

Recently, our group developed a cross–linked graphene sponge (CGS) acting as hemostatic material, which displays remarkable liquid adsorption capacity, thus resulting in a rapid hemostasis within 4 min [14]. Because of its good biocompatibility, this kind of graphene-based sponge is proved to be a platform to load different kinds of hemostatic materials [[15], [16], [17]]. Changing the cross linker from ethanediamine (EDA) to diaminopropionic acid could improve approximate half minutes for hemostatic performance [15], while the CGS combined with thrombin would stop bleeding within 100 s [16]. Recently, we used the CGS to anchor montmorillonite (MMT), the obtained graphene/MMT composite sponge (GMCS) presented remarkable characteristic, which effectively stopped bleeding in approximately 85 s in rabbit artery injury test [17]. Although GMCS eliminates the side effects of MMT, it is still a psychological disorder that the Food and Drug Administration has limited the usage of MMT as commercial hemostatic products since 2007 due to the risk of thrombosis via blood contact. Therefore, on the basis of those above-mentioned achievements and the demand of risk-free hemostasis, we try to develop a more appropriate agent with higher biosafety.

Kaolin is a natural aluminosilicate mineral [[18], [19], [20]]. It is well known for its remarkable ability to induce and accelerate blood clotting. Since 1950s, kaolin has been used as activating agent for clotting in medical doctor routinely performances. Up to now, kaolin still acts as ingredient for operation hemostasis [20,21]. The formed blood clots could effectively trap kaolin particles in the site of the injury, no risk of wandering their going deep into the body. In particular, in April 2008 the US naval medical research institute announced the successful introduce kaolin into ordinary gauze, which is one choice of hemostats for all branches of the US military [22]. As reported, kaolin could activate Factor XII and platelets to start the clotting cascade in vivo [20,23,24]. More importantly, kaolin has a good biocompatibility [25]. These outstanding properties highlight that kaolin is a valuable alternative substance.

Herein, we present a graphene-kaolin composite sponge (GKCS), which is synthesized by a facile hydrothermal reaction with graphene oxide (GO) sheets, EDA and kaolin powders (Scheme 1). GO and EDA mainly form the sponge framework, while kaolin powders will be embedded in to act as a new stimulation. GKCS will inherit remarkable liquid absorption capacity due to the porous structure inside, which is the key feature for this graphene-based hemostatic sponge. It can be expected that embedded kaolin into GKCS could improve its hemostatic performance especially with a risk-free way. GKCS is a new step to pursue excellence in traumatic hemostasis, on the platform of graphene-based materials.