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Effective hemostasis is vital to reduce pain and mortality of patients and the research and development of hemostatic materials are prerequisites for effective hemostasis. chitosan with good biodegradability, biocompatibility, and nontoxicity have been widely applied in biomedicine, the chemical industry, the food industry, and cosmetics. The excellent hemostatic properties have been studied extensively. As a result, chitosan-based composite hemostatic materials have been emerging. We will discuss the hemostatic mechanism of chitosan briefly and then progress to chitosan-based composite hemostatic materials to various forms like films, sponges, hydrogels, particles, and fibers. Finally future perspective of chitosan-based composite hemostatic materials.
Introduction
Hemostasis is a vital step in emergency care. Effective and quick hemostasis is critically important in surgical care and emergent trauma particularly for trauma cause in battlefields and other complicated situations. Hemostatic materials currently available in the market include collagen, gelatin, alginate, chitosan, oxidized cellulose, cyanoacricylic acid tissue, adhesive and porous zeolite. All these have an effective hemostatic function but there are some disadvantages as well. Collagen has limited hemostatic efficacy because it relies totally on the activating platelets to stop bleeding and has poor tissue adhesion. Porous zeolite will release a great amount of heat when it absorbed moisture from the blood. Cellulose dressing cannot be degraded in the wound and easily causes scars when being removed. Recently different hemostatic agents have been developing but most of them are ineffective in stopping bleeding and expensive or cause safety concerns. Thus there is a great interest to develop novel effective hemostats in hemostasis.
Chitosan is a natural polycationic polysaccharide that has been obtained from different sources like shrimp, crab, and certain fungi. It is multifunctional material with good compatibility no immunogenicity and no skin irritation. It is approved by FDs food drug administration in the USA and grass Generally recognized as safe. Currently, several FDA approved chitosan hemostatic products are being used. However, it is still a challenge to enhance their potential. Chitosan-based composite hemostatic materials refer to a series of novel multi-effect hemostats prepared by combining physically and chemically modified chitosan. Composite materials have attracted much attention due to their potential synergistic effects that can result in high performance. Therefore chitosan-based hemostatic materials are becoming more and more extensive in applications. So far many novels based chitosan composite based materials are becoming more and more effective in fast hemostasis and functional hemostasis.
Hemostatic mechanism of chitosan.
As early as 1964 the waterfall theory of blood coagulation was put forward which laid the foundation of the study of the coagulation pathway. The conventional hemostat facilitates the blood clotting by achieving a certain aspect .described in the waterfall theory. However many studies have shown that chitosan triggered coagulation without activation of intrinsic pathway including that hemostatic mechanism of chitosan was independent of the classical coagulation cascade. Although it is not clearly understood yet the hemostatic coagulation involved the following aspect.
A. Aggregation of red blood cells
the red blood cell the main kind of hemocyte in the blood, increases the blood viscosity and enhances the transportation of platelets to a vascular wall for physiological hemostasis. On the surface of the RBC cell membrane, some various proteins and glycolipids are negatively charged. In the physiological state, the aggregation and adhesion of RBC are inhibited owing to electrostatic repulsion. Chitosan is a natural cationic alkaline polysaccharide. it interacts with the RBC leading to intensive aggregation of RBC around the wound site to form blood clots that quickly stop bleeding. therefore the degree of protonation of amino acids on chitosan plays an important role in the adsorption of red blood cells. Studies have shown that the ability of chitosan to initiate coagulation was related to the percent of deacetylation and was more dependant on the amino group. Additionally, the interaction of chitosan with red blood cells increased with an increase in the molecular weight which may be explained by increased entanglement degree due to special intermolecular hydrogen bonding force or repulsion between the molecules.
B. Stimulation of platelets:
Under normal physiological conditions, platelets do not adhere to endothelial cells. However, in wounds, the activation of platelet adhesion and aggregation plays an important role in the process of hemostasis. Biopolymers can initiate activation of the platelet adhesion and aggregation which is a complex process and dependent on a variety of properties including surface chain mobility and surface chemical composition hydrogen bonding properties. Some studies showed that chitosan could enhance the activation of platelets and accelerate the adhesion and aggregation of platelets. The neutralization of the positive charge on chitosan resulted in a decrease in the number of adherent platelets and aggregates and no significant effect on coagulation activation indicating that a high positive charge density in chitosan was necessary to cause an increase in platelet aggregation and adhesion.
C. Contact system activation:
The contact of biomaterial surface with blood directly affects blood coagulation by modifying the protein function after adsorption which is called the contact activation pathway. The pathways include coagulation factors eleven and twelve. Contact of blood with functional biomaterials may produce two biological processes, including platelet adhesion and contact system activation which have a strong synergistic effect on biomaterial induced blood coagulation. studies show that chitosan induced blood coagulation is independent of all coagulation factors.
D. Formation of spatial network structure:
Chitosan has a series of reactions which are biochemical in vivo by combining with all plasma proteins and some of the important blood coagulation factors and thus strengthen the blood clots. However, studies concerning the activation of the contact system on the chitosan surface were noted. And the conclusions are still controversial. Consider the molecular structure, chitosan is a glycosaminoglycan which makes it easier to construct a network structure thus promoting the interaction of blood components with chitosan and facilitating the formation of strong blood clotting. A resulting three-dimensional network was bridged between chitosan chains and blood cells which could potentially halt the flow of blood.
