Uncontrolled hemorrhage arising from surgery or trauma may cause morbidity and even mortality. Therefore, facilitating control of severe bleeding is imperative for health care worldwide. Among diverse hemostatic materials, chitosan (CS) is becoming the most promising material owing to its non-toxic feature, as well as inherently hemostatic performance. However, further enhancing hemostatic property of CS-based materials without compromising more beneficial functions remains a challenge. In this review, representative hemostatic mechanisms of CS-based materials are firstly discussed in detail, mostly including red blood cells (RBCs) aggregation, platelet adherence and aggregation, as well as interaction with plasma proteins. Also, various forms (involving powder/particle, sponge, hydrogel, nanofiber, and other forms) of CS-based hemostatic materials are systematically summarized, mainly focusing on their design and preparation, characteristics, and comparative analysis of various forms. In addition, varied hemostatic applications are described in detail, such as skin wound hemostasis, liver hemostasis, artery hemostasis, and heart hemostasis. Finally, current challenges and future directions of functional design of CS-based hemostatic materials in diverse hemostatic applications are proposed to inspire more intensive researches. 

Recent advances of chitosan as a hemostatic material: Hemostatic mechanism, material design and prospective application

Chitosan and gelatin were the most widely used natural materials in pharmaceutical and medical fields, especially as local hemostatic agents, independently or as a composite material with the addition of other active substances. Chitosan and gelatin have excellent properties in biocompatibility, biodegradability, non-toxicity and water absorption capacity. The objective of this review was to analyze the characteristics of chitosan-gelatin (CG) composite-based biomaterial and its effectivity as a local hemostatic agent. We used PRISMA guidelines and the PICO framework to compile this review. The findings demonstrated that the CG composite-based biomaterial had excellent physical, chemical, mechanical properties and local hemostatic agent activity by adding other active substances such as oxidized fibers (OF), silica nanoparticles (SiNPs), calcium (Ca) and biphasic calcium phosphate (BCP) or by setting the CG composite proportion ratio.

/pdf/characterization-and-analysis-of-chitosan-gelatin-composite-2yypihe6.pdf

Characterization and Analysis of Chitosan-Gelatin Composite-Based Biomaterial Effectivity as Local Hemostatic Agent: A Systematic Review

Severe traumatic bleeding may lead to extremely high mortality rates, and early intervention to stop bleeding plays as a critical role in saving lives. However, rapid hemostasis in deep non-compressible trauma using a highly water-absorbent hydrogel, combined with strong tissue adhesion and bionic procoagulant mechanism, remains a challenge. In this study, a DNA hydrogel (DNAgel) network composed of natural nucleic acids with rapid water absorption, high swelling and instant tissue adhesion is reported, like a band-aid to physically stop bleeding. The excellent swelling behavior and robust mechanical performance, meanwhile, enable the DNAgel band-aid to fill the defect cavity and exert pressure on the bleeding vessels, thereby achieving compression hemostasis for deep tissue bleeding sites. The neutrophil extracellular traps (NETs)-inspired DNAgel network also acts as an artificial DNA scaffold for erythrocytes to adhere and aggregate, and activates platelets, promoting coagulation cascade in a bionic way. The DNAgel achieves lower blood loss than commercial gelatin sponge (GS) in male rat trauma models. In vivo evaluation in a full-thickness skin incision model also demonstrates the ability of DNAgel for promoting wound healing. Overall, the DNAgel band-aid with great hemostatic capacity is a promising candidate for rapid hemostasis and wound healing. 

Neutrophil extracellular traps-inspired DNA hydrogel for wound hemostatic adjuvant

A biodegradable micro/nano-structured porous hemostatic gelatin-based sponge as a dentistry surgery foam was prepared using a freeze-drying method. In vitro function evaluation tests were performed to ensure its hemostatic effect. Biocompatibility tests were also performed to show the compatibility of the sponge on human fetal foreskin fibroblasts (HFFF2) cells and red blood cells (RBCs). Then, 10 patients who required the extraction of two teeth were selected, and after teeth extraction, for dressing, the produced sponge was placed in one of the extracavities while a commercial sponge was placed in the cavity in the other tooth as a control. The total weight of the absorbed blood in each group was compared. The results showed a porous structure with micrometric and nanometric pores, flexibility, a two-week range for degradation, and an ability to absorb blood 35 times its weight in vitro. The prepared sponge showed lower blood clotting times (BCTs) (243.33 ± 2.35 s) and a lower blood clotting index (BCI) (10.67 ± 0.004%) compared to two commercial sponges that displayed its ability for faster coagulation and good hemostatic function. It also had no toxic effects on the HFFF2 cells and RBCs. The clinical assessment showed a better ability of blood absorption for the produced sponge (p-value = 0.0015). The sponge is recommended for use in dental surgeries because of its outstanding abilities.

/pdf/a-biodegradable-flexible-micro-nano-structured-porous-1i4jtueq.pdf

A Biodegradable Flexible Micro/Nano-Structured Porous Hemostatic Dental Sponge

Objective: Study the repair effect of tilapia collagen on acute wounds, and the effect on the expression level of related genes and its metabolic direction in the repair process. Materials and methods: After the full-thickness skin defect model was constructed in standard deviation rats, the wound healing effect was observed and evaluated by means of characterization, histology, and immunohistochemistry. RT-PCR, fluorescence tracer, frozen section and other techniques were used to observe the effect of fish collagen on the expression of related genes and its metabolic direction in the process of wound repair. Results: After implantation, there was no immune rejection reaction, fish collagen fused with new collagen fibers in the early stage of wound repair, and was gradually degraded and replaced by new collagen in the later stage. It has excellent performance in inducing vascular growth, promoting collagen deposition and maturation, and re-epithelialization. The results of fluorescent tracer showed that fish collagen was decomposed, and the decomposition products were involved in the wound repair process and remained at the wound site as a part of the new tissue. RT-PCR results showed that, without affecting collagen deposition, the expression level of collagen-related genes was down-regulated due to the implantation of fish collagen. Conclusion: Fish collagen has good biocompatibility and wound repair ability. It is decomposed and utilized in the process of wound repair to form new tissues.

/pdf/effects-and-metabolism-of-fish-collagen-sponge-in-repairing-801j1sag.pdf

Effects and metabolism of fish collagen sponge in repairing acute wounds of rat skin

Effective control of acute wound hemorrhage caused by battlefields, car accidents, natural disasters can highly improve patients’ survival rates. Nevertheless, hemostatic materials on present market have various defects and limitations. This study utilizes tilapia to extract macromolecular type I collagen to prepare a new hemostatic sponge for controlling acute wound bleeding. The extracted fish collagen has high purity, uniform molecular size and high hydroxyproline content. The peptide chain structure and natural high-level structure are intactly preserved. The infrared absorption spectrum showcases that it preserves all the characteristic absorption bands of type I collagen. The developed hemostatic sponge has a uniform honeycomb-shaped porous structure and high water absorption capacity. The biological safety test illustrates that the sponge cell has good compatibility and it will not trigger any inflammatory reaction or immune rejection reactions in the body. The sponge cell could be degraded gradually and completely, which has good biocompatibility and degradation performance. The result of in vitro experiments shows that certain groups or structures in fish collagen molecules can combine specific sites on the surface of blood cells and platelets, which can quickly activate platelets and coagulation system to obtain better coagulation function. The result of In vivo experiments further shows that the fish collagen sponge has fast coagulation speed and low bleeding during the hemostasis process of rabbit ear arteries and rat liver wounds, which proves that it has excellent coagulation performance.

Preparation of Super Absorbent and Highly Active Fish Collagen Sponge and its Hemostatic Effect in vivo and in vitro

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Preparation of Super Absorbent and Highly Active Fish Collagen Sponge and its Hemostatic Effect in vivo and in vitro

Effects and metabolism of fish collagen sponge in repairing acute wounds of rat skin