CaCO3–Chitosan Composites Granules for Instant Hemostasis and Wound Healing

Abstract

Excessive bleeding induces a high risk of death and is a leading cause of deaths that result from traffic accidents and military conflict. In this paper, we developed a novel porous chitosan–CaCO3 (CS–CaCO3) composite material and investigated its hemostatic properties and wound healing performance. The CS–CaCO3 composites material was prepared via a wet-granulation method. Granulation increases the infiltrating ability of the CS–CaCO3 composites material. The improved water absorption ability was enhanced to 460% for the CS–CaCO3 composites material compared to the CaCO3 or chitosan with only one single component. The coagulation studies in vivo illustrated that the blood clotting time was greatly reduced from 31 s for CaCO3 to 16 s for the CS–CaCO3 composite material. According to the results of the wound healing experiments in rats, it was found that the CS–CaCO3 composite material can promote wound healing. The CS–CaCO3 composite material could accelerate wound healing to a rate of 9 days, compared with 12 days for the CaCO3. The hemostatic activity, biocompatibility, and low cost of CS–CaCO3 composite material make it a potential agent for effective hemostatic and wound healing materials.

Calcium carbonate: controlled synthesis, surface functionalization, and nanostructured materials

“…259 CaCO 3 -CS composites have been prepared via a freeze-drying process. 256 These composites can accelerate wound healing; healing wounds over 9 days compared to the 12 days taken for pure CaCO 3 to achieve the same goal. However, the low water solubility of CS in neutral pH solution limits its further application in clinical wound healing.…”

“…In traditional Chinese medicine, powdered cuttlebone, a hemostatic material that mainly consists of CaCO 3 , can be orally administered to rapidly stop bleeding. 256,257 It is important to note that only 0.15 mM of CaCO 3 can be dissolved in water at room temperature, which is lower than the concentration of Ca 2+ in human blood (2.15–2.65 mM). 52 CaCO 3 , in the form of microspheres that exhibit high porosity and strong adsorption capacity, can be employed in irregular-shaped wounds.…”

“…52 CaCO 3 , in the form of microspheres that exhibit high porosity and strong adsorption capacity, can be employed in irregular-shaped wounds. While the use of CaCO 3 microspheres alone does not stop rapid bleeding, CaCO 3 –CS composites, 256 CaCO 3 –CS acetate hydrogels, 51 thrombin (Thr)-loaded CaCO 3 microspheres, 52 and self-propelled CaCO 3 -based hemostatic particles 258 have been developed and successfully employed in wound healing. Ca 2+ ions together with Thr, are involved in the activation of coagulation factor XIII in the coagulation system.…”

A Top-Down Procedure for Synthesizing Calcium Carbonate-Enriched Chitosan from Shrimp Shell Wastes

“…One of the advantages of the proposed synthesis technology described in this study, derived from bypassing the demineralization step, refers to the lower consumption of energy and time, and implicitly reduced preparation costs. As a parallel, a study of He et al described the preparation of chitosan-based composites enriched with CaCO 3 , which included additional stages for preparing the enriched chitosan [ 27 ]. CaCO 3 was first synthesized, by colloidal crystallization from supersaturated solution, followed by filtration and drying.…”

Application of chitosan-based materials in surgical or postoperative hemostasis

“…Calcium itself, as a coagulation factor, activates the coagulation cascade and accelerates fibrinogen formation. He et al precipitated and mixed calcium carbonate on CS by wet granulation, which improved the hemostatic activity of the composites (He et al, 2021). The material preparation method is shown in Table 1.…”