Microspheres of Carboxymethyl Chitosan, Sodium Alginate, and Collagen as a Hemostatic Agent in Vivo

Abstract

In the search for biocompatible composite microspheres to be used as a hemostatic agent, in a previous study, we designed a novel biomaterial, consisting of composite microspheres containing three natural biological ingredients, carboxymethyl chitosan, sodium alginate and collagen (CSCM). Furthermore, the chemical and physical properties, hemostatic ability, biocompatibility and cytotoxicity were investigated in vitro. In this work, the in vivo hemostatic performance, wound healing, hemocompatibility, histocompatibility, and biodegradability were evaluated by a series of experiments. The results showed that CSCM could both stop bleeding and enhance healing efficiency by accelerating the clotting and the wound closure rate, suggesting that CSCM acts as a hemostat, and enhances wound healing. In addition, the CSCM material had negligible intracutaneous stimulation reactions and no obvious hemolytic reactions. More importantly, CSCM can be degraded in vivo without significant impacts on physiology, biochemistry, and organization. Thus, CSCM may be a useful tool to stop bleeding in emergency conditions in both military and civilian settings.

Composite Hemostatic Nonwoven Textiles Based on Hyaluronic Acid, Cellulose, and Etamsylate

“…In urology, quick hemostasis is very desirable in instances of uncontrollable bleeding [31,32]. Moreover, advanced wound healing, based on tissue regeneration and restoration of its function, are now the center of interest [33].…”

In vitro evaluation of the hyaluronic acid/alginate composite powder for topical haemostasis and wound healing

“…Among these, powder‐based haemostatic dressings have been considered as promising candidates for haemorrhage management because of its capability of being used for treating deep or irregular‐shaped wounds. One class of topical dressings is the mineral‐based haemostatic powders, which contain specific minerals, such as zeolite, kaolin, and smectite . These powders possess microporous structures, which allow them to act as molecular sieves, dehydrates the bleeding or oozing wounds to increase the concentration of coagulation factors upon administration.…”

“…Polysaccharides, the naturally derived polymers composed of repeating sugar blocks, have attracted much attention as promising candidates for arresting haemorrhage because of their impeccable biocompatibility, biodegradability, marginal immunoreactivity, and abundance in nature . Most importantly, the ease of preparation for these biomaterials allows them to be formulated in dry powder and granular forms with microporous structures to enlarge the blood absorption efficiency of haemostatic powders . In the recent decade, prominent products such as TraumaDex (microporous polysaccharide haemospheres obtained from potato starch) and Celox (CX) (chitosan‐based granules and flakes) have gained Food and Drug Administration (FDA) approval and revealed comparable efficiency in terms of haemostatic capacity and survival rate to the mineral‐based powders (QuikClot and Woundstat) .…”

“…One class of topical dressings is the mineral-based haemostatic powders, which contain specific minerals, such as zeolite, kaolin, and smectite. 8,12,13 These powders possess microporous structures, which allow them to act as molecular sieves, dehydrates the bleeding or oozing wounds to increase the concentration of coagulation factors upon administration. Besides, the electrostatic surface charges and the dissolved ionic products of the mineral powders are responsible for the activation of pro-coagulation factors and consequently facilitate the clotting process.…”

“…6,19,20 Most importantly, the ease of preparation for these biomaterials allows them to be formulated in dry powder and granular forms with microporous structures to enlarge the blood absorption efficiency of haemostatic powders. 12,21,22 In the recent decade, 5,23 Despite the reduced immunogenicity of the polysaccharide-based powders, several in vivo results demonstrated that mild to severe inflammatory responses at the surrounding tissues could be detected because of the presence of residual powders in the wound. 24,25 Therefore, the recommended procedures to attenuate the foreign body reactions are reducing the amount of haemostatic powders while administration, followed by exhaustive removal of the powders from wounds upon acquiring haemostasis.…”