Hydroxypropyl chitosan/ε-poly-l-lysine based injectable and self-healing hydrogels with antimicrobial and hemostatic activity for wound repair.

The biggest obstacle to treating wound healing continues to be the production of simple, inexpensive wound dressings that satisfy the demands associated with full process of repair at the same time. Herein, a series of injectable composite hydrogels were successfully prepared by a one-pot method by utilizing the Schiff base reaction as well as hydrogen bonding forces between hydroxypropyl chitosan (HCS), ε-poly-l-lysine (EPL), and 2,3,4-trihydroxybenzaldehyde (TBA), and multiple cross-links formed by the reversible coordination between iron (III) and pyrogallol moieties. Notably, hydrogel exhibits excellent physicochemical properties, including injectability, self-healing, water retention, and adhesion, which enable to fill irregular wounds for a long period, providing a suitable moist environment for wound healing. Interestingly, the excellent hemostatic properties of the hydrogel can quickly stop bleeding and avoid the serious sequelae of massive blood loss in acute trauma. Moreover, the powerful antimicrobial and antioxidant properties also protect against bacterial infections and reduce inflammation at the wound site, thus promoting healing at all stages of the wound. The study of biohydrogel with multifunctional integration of wound treatment and smart medical treatment is clarified by this line of research.

A macromolecular cross-linked alginate aerogel with excellent concentrating effect for rapid hemostasis.

Alginate-based materials present promising potential for emergency hemostasis due to their excellent properties, such as procoagulant capability, biocompatibility, low immunogenicity, and cost-effectiveness. However, the inherent deficiencies in water solubility and mechanical strength pose a threat to hemostatic efficiency. Here, we innovatively developed a macromolecular cross-linked alginate aerogel based on norbornene- and thiol-functionalized alginates through a combined thiol-ene cross-linking/freeze-drying process. The resulting aerogel features an interconnected macroporous structure with remarkable water-uptake capacity (approximately 9000 % in weight ratio), contributing to efficient blood absorption, while the enhanced mechanical strength of the aerogel ensures stability and durability during the hemostatic process. Comprehensive hemostasis-relevant assays demonstrated that the aerogel possessed outstanding coagulation capability, which is attributed to the synergistic impacts on concentrating effect, platelet enrichment, and intrinsic coagulation pathway. Upon application to in vivo uncontrolled hemorrhage models of tail amputation and hepatic injury, the aerogel demonstrated significantly superior performance compared to commercial alginate hemostatic agent, yielding reductions in clotting time and blood loss of up to 80 % and 85 %, respectively. Collectively, our work illustrated that the alginate porous aerogel overcomes the deficiencies of alginate materials while exhibiting exceptional performance in hemorrhage, rendering it an appealing candidate for rapid hemostasis.

Study on the Compositional Analysis, Extraction Process, and Hemostatic and Anti-Inflammatory Activities of Cirsium japonicum Fisch. ex DC.-Cirsium setosum (Willd.) MB Extracts.

Cirsium japonicum Fisch. ex DC. (CF) and Cirsium setosum (Willd.) MB (CS) are commonly used clinically to stop bleeding and eliminate carbuncles. Still, CF is mainly used for treating inflammation, while CS favors hemostasis. Therefore, the present study used UHPLC-MS to analyze the main chemical constituents in CF-CS extract. We optimized the extraction process using single-factor experiments and response surface methodology. Afterward, the hemostatic and anti-inflammatory effects of CF-CS extract were investigated by determining the clotting time in vitro, the bleeding time of rabbit trauma, and the induction of rabbit inflammation using xylene and lipopolysaccharide. The study of hemostatic and anti-inflammatory effects showed that the CF-CS, CF, and CS extract groups could significantly shorten the coagulation time and bleeding time of rabbits compared with the blank group (p < 0.01); compared with the model group, it could dramatically inhibit xylene-induced ear swelling in rabbits and the content of TNF-α, IL-6, and IL-1ß in the serum of rabbits (p < 0.01). The results showed that combined CF and CS synergistically increased efficacy. CF-CS solved the problem of the single hemostatic and anti-inflammatory efficacy of a single drug, which provided a new idea for the research and development of natural hemostatic and anti-inflammatory medicines.

Evaluation of hemostatic, anti-inflammatory, wound healing, skin irritation and allergy, and antimicrobial properties of active fraction from the ethanol extract of Chromolaena odorata (L.) R.M. King & H. Rob.

ETHNOPHARMACOLOGICAL RELEVANCE: Chromolaenaodorata (L.) R.M. King & H. Rob, a perennial herb, has been traditionally utilized as a herbal remedy for treating leech bites, soft tissue wounds, burn wounds, skin infections, and dento-alveolitis in tropical and subtropical regions. AIM OF THE STUDY: The present study was to analyze the active fraction of C. odorata ethanol extract and investigate its hemostatic, anti-inflammatory, wound healing, and antimicrobial properties. Additionally, the safety of the active fraction as an external preparation was assessed through skin irritation and allergy tests. MATERIALS AND METHODS: The leaves and stems of C. odorata were initially extracted with ethanol, followed by purification through AB-8 macroporous adsorption resin column chromatography to yield different fractions. These fractions were then screened for hemostatic activity in mice and rabbits to identify the active fraction. Subsequently, the hemostatic effect of the active fraction was assessed through the bleeding time of the rabbit ear artery in vivo and the coagulant time of rabbit blood in vitro. The anti-inflammatory activity of the active fraction was tested on mice ear edema induced by xylene and rat paw edema induced by carrageenin. Furthermore, the active fraction's promotion effect on wound healing was evaluated using a rat skin injury model, and skin safety tests were conducted on rabbits and guinea pigs. Lastly, antimicrobial activities against two Gram-positive bacteria (G+, Staphylococcus aureus and S. epidermidis) and three Gram-negative bacteria (G-, Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa) were determined using the plate dilution method. RESULTS: The ethanol extract of C. odorata leaves and stems was fractionated into 30%, 60%, and 90% ethanol eluate fractions. These fractions demonstrated hemostatic activity, with the 30% ethanol eluate fraction (30% EEF) showing the strongest effect, significantly reducing bleeding time (P < 0.05). A concentration of 1.0 g/mL of the 30% EEF accelerated cutaneous wound healing in rats on the 3rd, 6th, and 9th day post-operation, with the healing effect increasing over time. No irritation or allergy reactions were observed in rabbits and guinea pigs exposed to the 30% EEF. Additionally, the 30% EEF exhibited mild inhibitory effect on mice ear and rat paw edema, as well as antimicrobial activity against tested bacteria, with varying minimal inhibitory concentration (MIC) values. CONCLUSIONS: The 30% EEF demonstrated a clear hemostatic effect on rabbit bleeding time, a slight inhibitory effect on mice ear edema and rat paw edema, significant wound healing activity in rats, and no observed irritation or allergic reactions. Antibacterial activity was observed against certain clinically isolated bacteria, particularly the G- bacteria. This study lays the groundwork for the potential development and application of C. odorata in wound treatment.

Multihydrogen Bond Modulated Polyzwitterionic Removable Adhesive Hydrogel with Antibacterial and Hemostatic Function for Wound Healing.

Wound management is a major challenge worldwide, placing a huge financial burden on the government of every nation. Wound dressings that can protect wounds, accelerate healing, prevent infection, and avoid secondary damage continue to be a major focus of research in the health care and clinical communities. Herein, a novel zwitterionic polymer (LST) hydrogel incorporated with [2-(methacryloyloxy) ethyl] dimethyl-(3-sulfopropyl) ammonium hydroxide (SBMA), mussel-inspired N-[tris(hydroxymethyl)methyl] acrylamide (THMA), and lithium magnesium salt was prepared for functional wound dressings. The incorporation of the THMA monomer containing three hydroxyl groups gives the hydrogel suitable adhesion properties (∼6.0 KPa). This allows the LST zwitterionic hydrogels to bind well to the skin, which not only protects the wound and ensures its therapeutic efficacy but also allows for painless removal and reduced patient pain. Zwitterionic sulfobetaine units of SBMA provide antimicrobial and mechanical properties. The chemical structure and microscopic morphology of LST zwitterionic hydrogels were systematically studied, along with their swelling ratio, adhesion, and mechanical properties. The results showed that the LST zwitterionic hydrogels had a uniform and compact porous structure with the highest swelling and mechanical strain of 1607% and 1068.74%, respectively. The antibacterial rate of LST zwitterionic hydrogels was as high as 99.49%, and the hemostatic effect was about 1.5 times that of the commercial gelatin hemostatic sponges group. In further studies, a full-thickness mouse skin model was selected to evaluate the wound healing performance. Wounds covered by LST zwitterionic hydrogels had a complete epithelial reformation and new connective tissue, and its vascular regenerative capacity was increased to about 2.4 times that of the commercial group, and the wound could completely heal within 12-13 days. This study provides significant advances in the design and construction of multifunctional zwitterionic hydrogel adhesives and wound dressings.

Hemostatic and Ultrasound-Controlled Bactericidal Silk Fibroin Hydrogel via Integrating a Perfluorocarbon Nanoemulsion.

Excessive blood loss and infections are the prominent risks accounting for mortality and disability associated with acute wounds. Consequently, wound dressings should encompass adequate adhesive, hemostatic, and bactericidal attributes, yet their development remains challenging. This investigation presented the benefits of incorporating a perfluorocarbon nanoemulsion (PPP NE) into a silk-fibroin (SF)-based hydrogel. By stimulating the ß-sheet conformation of the SF chains, PPP NEs drastically shortened the gelation time while augmenting the elasticity, mechanical stability, and viscosity of the hydrogel. Furthermore, the integration of PPP NEs improved hemostatic competence by boosting the affinity between cells and biomacromolecules. It also endowed the hydrogel with ultrasound-controlled bactericidal ability through the inducement of inner cavitation by perfluorocarbon and reactive oxygen species (ROS) generated by the sonosensitizer protoporphyrin. Ultimately, we employed a laparotomy bleeding model and a Staphylococcus aureus-infected trauma wound to demonstrate the first-aid efficacy. Thus, our research suggested an emulsion-incorporating strategy for managing emergency wounds.

Dragon's Blood-Loaded Mesoporous Silica Nanoparticles for Rapid Hemostasis and Antibacterial Activity.

Dragon's blood (DB) is a traditional Chinese medicine (TCM) with hemostatic effects and antibacterial properties. However, it is still challenging to use for rapid hemostasis because of its insolubility. In this study, different amounts of DB were loaded on mesoporous silica nanoparticles (MSNs) to prepare a series of DB-MSN composites (5DB-MSN, 10DB-MSN, and 20DB-MSN). DB-MSN could quickly release DB and activate the intrinsic blood coagulation cascade simultaneously by DB and MSN. Hemostasis tests demonstrated that DB-MSN showed superior hemostatic effects than either DB or MSNs alone, and 10DB-MSN exhibited the best hemostatic effect. In addition, the antibacterial activities of DB-MSN against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) improved with the increase in DB. Furthermore, the hemolysis assay and cytocompatibility assay demonstrated that all DB-MSNs exhibited excellent biocompatibility. Based on these results, 10DB-MSN is expected to have potential applications for emergency hemostatic and antibacterial treatment in pre-hospital trauma.

The study of double-network carboxymethyl chitosan/sodium alginate based cryogels for rapid hemostasis in noncompressible hemorrhage.

Developing an injectable hemostatic dressing with shape recovery and high blood absorption ratio for rapid hemostasis in noncompressible hemorrhage maintains a critical clinical challenge. Here, double-network cryogels based on carboxymethyl chitosan, sodium alginate, and methacrylated sodium alginate were prepared by covalent crosslinking and physical crosslinking, and named carboxymethyl chitosan/methacrylated sodium alginate (CM) cryogels. Covalent crosslinking was achieved by methacrylated sodium alginate in the freeze casting process, while physical crosslinking was realized by electrostatic interaction between the amino group of carboxymethyl chitosan and the carboxyl group of sodium alginate. CM cryogels exhibited large water swelling ratios (8167 ± 1062 %), fast blood absorption speed (2974 ± 669 % in 15 s), excellent compressive strength (over 160 kPa for CM100) and shape recovery performance. Compared with gauze and commercial gelatin sponge, better hemostatic capacities were demonstrated for CM cryogel with the minimum blood loss of 40.0 ± 8.9 mg and the lowest hemostasis time of 5.0 ± 2.0 s at hemostasis of rat liver. Made of natural polysaccharides with biocompatibility, hemocompatibility, and cytocompatibility, the CM cryogels exhibit shape recovery and high blood absorption rate, making them promising to be used as an injectable hemostatic dressing for rapid hemostasis in noncompressible hemorrhage.

Enhanced physiochemical, antibacterial, and hemostatic performance of collagen-quaternized chitosan-graphene oxide sponges for promoting infectious wound healing.

Bacteria-infected wound healing has attracted widespread attention in biomedical engineering. Wound dressing is a potential strategy for repairing infectious wounds. However, the development of wound dressing with appropriate physiochemical, antibacterial, and hemostatic properties, remains challenging. Hence, there is a motivation to develop new synthetic dressings to improve bacteria-infected wound healing. Here, we fabricate a biocompatible sponge through the covalent crosslinking of collagen (Col), quaternized chitosan (QCS), and graphene oxide (GO). The resulting Col-QCS-GO sponge shows an elastic modulus of 1.93-fold higher than Col sponge due to enhanced crosslinking degree by GO incorporation. Moreover, the fabricated Col-QCS-GO sponge shows favorable porosity (84.30 ± 3.12 %), water absorption / retention (2658.0 ± 113.4 % / 1114.0 ± 65.7 %), and hemostasis capacities (blood loss <50.0 mg). Furthermore, the antibacterial property of the Col-QCS-GO sponge under near-infrared (NIR) irradiation is significantly enhanced (the inhibition rates are 99.9 % for S. aureus and 99.9 % for E. coli) due to the inherent antibacterial properties of QCS and the photothermal antibacterial capabilities of GO. Finally, the Col-QCS-GO+NIR sponge exhibits the lowest percentage of wound area (9.05 ± 1.42 %) at day 14 compared to the control group (31.61 ± 1.76 %). This study provides new insights for developing innovative sponges for bacteria-infected wound healing.

Sodium alginate/carboxycellulose/polydopamine composite microspheres for rapid hemostasis of deep irregular wounds.

Hemostasis of deep irregular wounds is a severe problem in clinical practice. The development of rapid-acting hemostatic agents for deep and irregular wound is urgently needed. Here, sodium alginate/carboxycellulose/polydopamine (SA/CNF/PDA) microspheres was prepared by reverse emulsification and crosslinking with Ca2+, and SA/CNF/PDA composite hemostatic microspheres with porous structure were obtained by freeze-drying. SA/CNF/PDA composite hemostatic microspheres exhibited excellent porosity and water absorption which could rapidly absorb blood on the wound surface. Moreover, SA/CNF/PDA composite microspheres demonstrated remarkable hemostatic capabilities both in vitro and in vivo. It exhibited strong hemostatic performance in models of mouse tail-break and liver damage. Especially in liver injury model, it was completely hemostatic in 95 s, and blood loss (19.3 mg). The hemostatic efficacy of the SA/CNF/PDA composite microspheres was amplified through the stimulation of both exogenous and endogenous coagulation pathways. Therefore, SA/CNF/PDA composite hemostatic microspheres are suitable for rapid hemostasis of deep irregular wounds which are potential rapid hemostatic material for surgical application.

Preparation of antibacterial hydrogel from poly(aspartic hydrazide) and quaternized N-[3-(dimethylamino) propyl] methylacrylamide copolymer with antioxidant and hemostatic effects for wound repairing.

Hydrogels as wound dressing have attracted extensive attention in past decade because they can provide moist microenvironment to promote wound healing. Herein, this research designed a multifunctional hydrogel with antibacterial property and antioxidant activity fabricated from quaternary ammonium bearing light emitting quaternized TPE-P(DAA-co-DMAPMA) (QTPDD) and poly(aspartic hydrazide) (PAH). The protocatechuic aldehyde (PCA) grafted to the hydrogel through dynamic bond endowed the hydrogel with antioxidant activity and the tranexamic acid (TXA) was loaded to enhance the hemostatic performance. The hydrogel possesses preferable gelation time for injectable application, good antioxidant property and tissue adhesion, improved hemostatic performance fit for wound repairing. Furthermore, the hydrogel has excellent antimicrobial property to both E. coli and S. aureus based on quaternary ammonium structure. The hydrogel also showed good biocompatibility and the in vivo experiments proved this hydrogel can promote the wound repairing rate. This study suggests that TXA/hydrogel with quaternary ammonium structure and dynamic grafted PCA have great potential in wound healing applications.

Characterization of a canine freeze-dried platelet-derived hemostatic agent: A preclinical model for surgical and traumatic hemorrhage.

INTRODUCTION: A freeze-dried, platelet-derived hemostatic agent (FPH) was developed for acute hemorrhage. The canine product (cFPH) was developed for use in preclinical models supporting human product (hFPH) investigations. MATERIALS AND METHODS: A carotid artery bypass graft (CABG) study in dogs compared 3 dosages of cFPH to canine liquid stored platelets (cLSP) and vehicle (VEH) control groups. Histopathological analysis and blood loss assessments were completed. A separate ex-vivo synthetic graft study assessed thrombogenicity via blood from human and canine donors that was combined with species-specific FPH or apheresis platelets. Characterization of cFPH and hFPH included thrombin generation, total thrombus formation, and scanning electron microscopy. RESULTS: Blood loss was reduced in CABG dogs receiving standard of care (cLSP) or cFPH treatment compared to VEH control; a cFPH dose effect signal was observed. Further, cFPH dosing up to 5 × 109 cells/kg was not associated with increased mortality or occlusion of the anastomosis sites, and histopathologic evidence of off-target thrombosis was not detected. When passed through a synthetic graft (ex vivo), whole blood combined with species-specific FPH did not result in thrombosis beyond that of whole blood control. In vitro testing and imaging of cFPH and FPH were comparable. CONCLUSIONS: A single dose of cFPH or cLSP reduced blood loss in a pilot surgical study and was well tolerated with no related adverse events. Further, the hemostatic activity and characteristics of cFPH are comparable to that of hFPH, suggesting that research findings from the canine product are likely to inform the development of the human product.

Advances of biological macromolecules hemostatic materials: A review.

Achieving hemostasis is a necessary intervention to rapidly and effectively control bleeding. Conventional hemostatic materials currently used in clinical practice may aggravate the damage at the bleeding site due to factors such as poor adhesion and poor adaptation. Compared to most traditional hemostatic materials, polymer-based hemostatic materials have better biocompatibility and offer several advantages. They provide a more effective method of stopping bleeding and avoiding additional damage to the body in case of excessive blood loss. Various hemostatic materials with greater functionality have been developed in recent years for different organs using diverse design strategies. This article reviews the latest advances in the development of polymeric hemostatic materials. We introduce the coagulation cascade reaction after bleeding and then discuss the hemostatic mechanisms and advantages and disadvantages of various polymer materials, including natural, synthetic, and composite polymer hemostatic materials. We further focus on the design strategies, properties, and characterization of hemostatic materials, along with their applications in different organs. Finally, challenges and prospects for the application of hemostatic polymeric materials are summarized and discussed. We believe that this review can provide a reference for related research on hemostatic materials, contributing to the further development of polymer hemostatic materials.

Nanofibrous composite from chitosan-casein polyelectrolyte complex for rapid hemostasis in rat models in vivo.

Bleeding causes ∼5.8 million deaths globally; half of the patients die if rapid hemostasis is not achieved. Here, we report a chitosan-casein (CC)-based nanofibrous polyelectrolyte complex (PEC) that could clot blood within 10 s in the rat femoral artery model in vivo. The nanofiber formation by self-assembly was also optimized for process parameters (concentration, mixing ratio, pH, and ultrasonication). Results showed that increasing the concentration of chitosan from 10 % to 90 % in the formulation increased the productivity (r = 0.99) of PECs but led to increased blood clotting time (r = 0.90) due to an increase in zeta potential (r = 0.98), fiber diameter (r = 0.93), and decreased surface porosity (r = -0.99), absorption capacity (r = -0.99). The pH also influenced the zeta potential of PEC, with an optimized pH of 8.0 ± 0.1 yielding clear nanofibers. Sonication improved the segregation of nanofibers by promoting water removal. The optimized PECs containing chitosan and casein in the ratio of 30:70 (CC30) at a pH of 8.0 and dehydration under sonication could clot the blood within 9 ± 2 s in vitro and 9 ± 2 s in rat femoral artery puncture model. The CC30 formulation did not cause any irritation or corrosion on rat skin. Histopathology and immunohistochemistry of various organs showed that CC30 was biocompatible and non-immunogenic under in vivo conditions.

The hemostatic performance and mechanism of palygorskite with structural regulate by oxalic acid gradient leaching.

Palygorskite (Pal) is a naturally available one-dimensional clay mineral, featuring rod-shaped morphology, nanoporous structure, permanent negative charges as well as abundant surface hydroxyl groups, exhibiting promising potential as a natural hemostatic material. In this study, the hemostatic performance and mechanisms of Pal were systematically investigated based on the structural regulate induced by oxalic acid (OA) gradient leaching from perspectives of structure, surface attributes and ion release.In vitroandin vivohemostasis evaluation showed that Pal with OA leaching for 1 h exhibited a superior blood procoagulant effect compared with the raw Pal as well as the others leached for prolonging time. This phenomenon might be ascribed to the synergistic effect of the intact nanorod-like morphology, the increase in the surface negative charge, the release of metal ions (Fe3+and Mg2+), and the improved blood affinity, which promoted the intrinsic coagulation pathway, the fibrinogenesis and the adhesion of blood cells, thereby accelerating the formation of robust blood clots. This work is expected to provide experimental and theoretical basis for the construction of hemostatic biomaterials based on clay minerals.

TAVAC: comprehensive review of currently available hemostatic products as adjunct to surgical hemostasis.

BACKGROUND: The use of hemostatic agents by general surgeons during abdominal operations is commonplace as an adjunctive measure to minimize risks of postoperative bleeding and its downstream complications. Proper selection of products can be hampered by marginal understanding of their pharmacokinetics and pharmacodynamics. While a variety of hemostatic agents are currently available on the market, the choice of those products is often confusing for surgeons. This paper aims to summarize and compare the available hemostatic products for each clinical indication and to ultimately better guide surgeons in the selection and proper use of hemostatic agents in daily clinical practice. METHODS: We utilized PubMed electronic database and published product information from the respective pharmaceutical companies to collect information on the characteristics of the hemostatic products. RESULTS: All commercially available hemostatic agents in the US are described with a description of their mechanism of action, indications, contraindications, circumstances in which they are best utilized, and expected results. CONCLUSION: Hemostatic products come with many different types and specifications. They are valuable tools to serve as an adjunct to surgical hemostasis. Proper education and knowledge of their characteristics are important for the selection of the right agent and optimal utilization.

Characterization of Three Polysaccharide-Based Hydrogels Derived from Laminaria japonica and Their Hemostatic Properties.

Three Laminaria japonica polysaccharides (LJPs) extracted via water extraction (LJP-W), acid extraction (LJP-A), and enzymatic extraction (LJP-E) were used as raw materials to be cross-linked with chitosan and polyvinyl alcohol to prepare hydrogels. Compared with conventional hydrogel systems, all three types of LJP-based polysaccharide hydrogels exhibited better swelling properties (14 times their original weight) and the absorption ability of simulated body fluid (first 2 h: 6-10%). They also demonstrated better rigidity and mechanical strength. Young's modulus of LJP-E was 4 times that of the blank. In terms of hemostatic properties, all three polysaccharide hydrogels did not show significant cytotoxic and hemolytic properties. The enzyme- and acid-extracted hydrogels (LJP-Gel-A and LJP-Gel-E) demonstrated better whole-blood coagulant ability compared with the water-extracted hydrogel (LJP-Gel-W), as evidenced by the whole blood coagulation index being half that of LJP-Gel-W. Additionally, the lactate dehydrogenase viabilities of LJP-Gel-A and LJP-Gel-E were significantly higher, at about four and three times those of water extraction, respectively. The above results suggested that LJP-Gel-A and LJP-Gel-E exhibited better blood coagulation capabilities than LJP-Gel-W, due to their enhanced platelet enrichment and adhesion properties. Consequently, these hydrogels are more conducive to promoting coagulation and have good potential for wound hemostasis.

Development of an efficient hemostatic material based on cuttlefish ink nanoparticles loaded in cuttlebone biocomposite.

Traumatic hemorrhage is one of the main causes of mortality in civilian and military accidents. This study aimed to evaluate the effectiveness of cuttlefish bone (cuttlebone, CB) and CB loaded with cuttlefish ink (CB-CFI) nanoparticles for hemorrhage control. CB and CB-CFI were prepared and characterized using different methods. The hemostasis behavior of constructed biocomposites was investigated in vitro and in vivo using a rat model. Results showed that CFI nanoparticles (NPs) are uniformly dispersed throughout the CB surface. CB-CFI10 (10 mg CFI in 1.0 g of CB) showed the best blood clotting performance in both in vitro and in vivo tests. In vitro findings revealed that the blood clotting time of CB, CFI, and CB-CFI10 was found to be 275.4 ± 12.4 s, 229.9 ± 19.9 s, and 144.0 ± 17.5 s, respectively. The bleeding time in rat liver injury treated with CB, CFI, and CB-CFI10 was 158.1 ± 9.2 s, 114.0 ± 5.7 s, and 46.8 ± 2.7 s, respectively. CB-CFI10 composite resulted in more reduction of aPTT (11.31 ± 1.51 s) in comparison with CB (17.34 ± 2.12 s) and CFI (16.79 ± 1.46 s) (p < 0.05). Furthermore, CB and CB-CFI10 exhibited excellent hemocompatibility. The CB and CB-CFI did not show any cytotoxicity on human foreskin fibroblast (HFF) cells. The CB-CFI has a negative surface charge and may activate coagulation factors through direct contact with their components, including CaCO3, chitin, and CFI-NPs with blood. Thus, the superior hemostatic potential, low cost, abundant, simple, and time-saving preparation process make CB-CFI a very favorable hemostatic material for traumatic bleeding control in clinical applications.

Chitosan/starch based unoxidized tannic acid modified microparticles for rapid hemostasis with broad spectrum antibacterial activity.

The development of a rapid hemostat through a facile method with co-existing antibacterial activity and minimum erythrocyte lysis property stands as a major requirement in the field of hemostasis. Herein, a series of novel microparticle hemostats were synthesized using chitosan, different hydrothermally-treated starches, and cross-linked with tannic acid (TA) simultaneously in an unoxidized environment via ionotropic gelation method. Hemostats' comparative functional properties, such as adjustable antibacterial and erythrocyte compatibility upon various starch additions were evaluated. The in vivo hemostatic study revealed that the developed hemostats for mouse liver laceration and rat tail amputation had clotting times (13 s and 38 s, respectively) and blood loss (51 mg and 62 mg, respectively) similar to those of Celox™. The erythrocyte adhesion test suggested that erythrocyte distortion can be lowered by modifying the antibacterial hemostats with different starches. The broad-spectrum antibacterial efficacy of the hemostats remained intact against S. aureus (>90 %), E. coli (>80 %), and P. mirabilis bacteria upon starch modification. They also demonstrated high hemocompatibility (<3 % hemolysis ratio), moderate cell viability (>81 %), in vivo biodegradation, and angiogenesis indicating adequate biocompatibility and wound healing. The developed hemostats hold significant promise to be employed as rapid hemostatic agents for preventing major bleeding and bacterial infection in emergencies.

Protamine-grafted carboxymethyl chitosan based hydrogel with adhesive and long-term antibacterial properties for hemostasis and skin wound healing.

In this study, we developed a tissue-adhesive and long-term antibacterial hydrogel consisting of protamine (PRTM) grafted carboxymethyl chitosan (CMC) (PCMC), catechol groups modified CMC (DCMC), and oxidized hyaluronic acid (OHA), named DCMC-OHA-PCMC. According to the antibacterial experiments, the PCMC-treated groups showed obvious and long-lasting inhibition zones against E. coli (and S. aureus), and the corresponding diameters varied from 10.1 mm (and 15.3 mm) on day 1 to 9.8 mm (and 15.3 mm) on day 7. The DCMC-OHA-PCMC hydrogel treated groups also exhibited durable antibacterial ability against E. coli (and S. aureus), and the antibacterial rates changed from 99.3 ± 0.21 % (and 99.6 ± 0.36 %) on day 1 to 76.2 ± 1.74 % (and 84.2 ± 1.11 %) on day 5. Apart from good mechanical and tissue adhesion properties, the hydrogel had excellent hemostatic ability mainly because of the grafted positive-charged PRTM. As the animal assay results showed, the hydrogel was conducive to promoting the deposition of new collagen (0.84 ± 0.03), the regeneration of epidermis (98.91 ± 6.99 µm) and wound closure in the process of wound repairing. In conclusion, the presented outcomes underline the prospective potential of the multifunctional CMC-based hydrogel for applications in wound dressings.