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1.
Carbohydr Polym ; 338: 122148, 2024 Aug 15.
Article En | MEDLINE | ID: mdl-38763731

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.


Alginates , Gels , Hemostasis , Hemostatics , Alginates/chemistry , Animals , Hemostatics/chemistry , Hemostatics/pharmacology , Hemostasis/drug effects , Gels/chemistry , Porosity , Hemorrhage/drug therapy , Blood Coagulation/drug effects , Mice , Male , Cross-Linking Reagents/chemistry , Biocompatible Materials/chemistry , Biocompatible Materials/pharmacology
2.
Carbohydr Polym ; 337: 122135, 2024 Aug 01.
Article En | MEDLINE | ID: mdl-38710549

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.


Chitosan , Hemostatics , Hydrogels , Polylysine , Wound Healing , Wound Healing/drug effects , Hydrogels/chemistry , Hydrogels/pharmacology , Chitosan/chemistry , Chitosan/pharmacology , Chitosan/analogs & derivatives , Polylysine/chemistry , Polylysine/pharmacology , Animals , Hemostatics/chemistry , Hemostatics/pharmacology , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Mice , Staphylococcus aureus/drug effects , Escherichia coli/drug effects , Humans , Anti-Infective Agents/pharmacology , Anti-Infective Agents/chemistry , Schiff Bases/chemistry , Schiff Bases/pharmacology , Rats
3.
Molecules ; 29(9)2024 Apr 23.
Article En | MEDLINE | ID: mdl-38731410

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.


Anti-Inflammatory Agents , Cirsium , Hemostatics , Plant Extracts , Animals , Rabbits , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/isolation & purification , Cirsium/chemistry , Hemostatics/pharmacology , Hemostatics/chemistry , Hemostatics/isolation & purification , Plant Extracts/pharmacology , Plant Extracts/chemistry , Chromatography, High Pressure Liquid , Inflammation/drug therapy , Inflammation/pathology , Male
4.
Zhongguo Zhong Yao Za Zhi ; 49(10): 2710-2721, 2024 May.
Article Zh | MEDLINE | ID: mdl-38812171

Studies have reported that the hemostatic effect of Sanguisorbae Radix(SR) is significantly enhanced after processing with charcoal. However, the standard components(tannins and gallic acid) specified in the Chinese Pharmacopeia decrease in charcoal-fried Sanguisorbae Radix(CSR), which is contrast to the enhancement of the hemostatic effect. Therefore, this study aimed to optimize the charcoal-frying process of SR based on its hemostatic efficacy and comprehensively analyze the components of SR and its processed products, thus exploring the material basis for the hemostatic effect. The results indicated that SR processed at 250 ℃ for 14 min(14-min CSR) not only complied with the description in the Chinese Pharmacopeia but also demonstrated improved blood-coagulating and blood-adsorbing effects compared with raw SR(P<0.05). Moroever, 14-min CSR reduced the bleeding time in the rat models of tail snipping, liver bleeding, and muscle injury, surpassing both raw and excessively fried SR(16 min processed) as well as tranexamic acid(P<0.05). Ellagitannin, ellagic acid, methyl gallate, pyrogallic acid, protocatechuic acid, Mg, Ca, Mn, Cu, and Zn contributed to the hemostatic effect of CSR over SR. Among these substances, ellagitannin, ellagic acid, Mg, and Ca had high content in the 14 min CSR, reaching(106.73±14.87),(34.86±4.43),(2.81±0.23), and(1.21±0.23) mg·g~(-1), respectively. Additionally, the color difference value(ΔE~*ab) of SR processed to different extents was correlated with the content of the aforementioned hemostatic substances. In summary, this study optimized the charcoal-frying process as 250 ℃ for 14 min for SR based on its hemostatic effect. Furthermore, ellagic acid and/or the powder chromaticity are proposed as indicators for the processing and quality control of CSR.


Charcoal , Drugs, Chinese Herbal , Hemostatics , Rats, Sprague-Dawley , Sanguisorba , Animals , Rats , Drugs, Chinese Herbal/chemistry , Drugs, Chinese Herbal/pharmacology , Hemostatics/pharmacology , Hemostatics/chemistry , Sanguisorba/chemistry , Charcoal/chemistry , Male , Cooking , Blood Coagulation/drug effects , Humans
5.
Acta Biomater ; 181: 249-262, 2024 Jun.
Article En | MEDLINE | ID: mdl-38704113

Endoscopic surgery is an effective and common clinical practice for chronic sinusitis. Nasal packing materials are applied in nasal surgery to prevent hemorrhage and promote wound healing. In this study, a degradable polyurethane foam dressing is successfully developed as a promising nasal packing material with good biocompatibility and antibacterial capability. Specifically, quaternized chitosan (QCS) serves as the crosslinker instead of polyols to offer polyurethane foam (PUF-QCS) antibacterial capability. The PUF-QCS2.0 % (with 2.0 wt% QCS) exhibits satisfactory liquid absorption capacity (19.4 g/g), high compressive strengths at both wet (14.5 kPa) and dry states (7.7 kPa), and a good degradation rate (8.3 %) within 7 days. Meanwhile, PUF-QCS2.0 % retains long-term antibacterial activity for 7 days and kills 97.3 % of S. aureus and 91.8 % of E. coli within 6 hours in antibacterial testing. Furthermore, PUF-QCS2.0 % demonstrates a positive hemostatic response in the rabbit nasal septum mucosa trauma model by reducing hemostatic time over 50.0 % and decreasing blood loss up to 76.1 % compared to the commercial PVA nasal packing sponge. Importantly, PUF-QCS also exhibits a significant antibacterial activity in nasal cavity. This nasal packing material has advantages in post-surgery bleeding control and infection prevention. STATEMENT OF SIGNIFICANCE: The performance of a nasal packing sponge requires good mechanical properties, fast and high liquid absorption rate, effective degradability and strong antibacterial activity. These features are helpful for improving the postoperative recovery and patient healing. However, integrating these into a single polyurethane foam is a challenge. In this study, quaternized chitosan (QCS) is synthesized and used as a chain extender and antibacterial agent in preparing a degradable polyurethane foam (PUF-QCS) dressing. PUF-QCS undergoes partial degradation and exhibits effective broad-spectrum antibacterial activity in 7 days. The reduction of postoperative bleeding and infection observed in the animal experiment further demonstrates that the PUF-QCS developed here outperforms the existing commercial nasal packing materials.


Anti-Bacterial Agents , Chitosan , Polyurethanes , Polyurethanes/chemistry , Polyurethanes/pharmacology , Chitosan/chemistry , Chitosan/pharmacology , Rabbits , Animals , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Hemostasis/drug effects , Staphylococcus aureus/drug effects , Hemostatics/chemistry , Hemostatics/pharmacology , Bandages , Escherichia coli/drug effects , Male
6.
Int J Biol Macromol ; 270(Pt 2): 132440, 2024 Jun.
Article En | MEDLINE | ID: mdl-38761899

Hemostatic powder is widely utilized in emergency situations to control bleeding due to its ability to work well on wounds with irregular shapes, ease of application, and long-term stability. However, traditional powder often suffers from limited tissue adhesion and insufficient support for blood clot formation, leaving it susceptible to displacement by the flow of blood. This study introduces a hemostatic powder composed of tannic modified mesoporous bioactive glass (TMBG), cationic quaternized chitosan (QCS), and anionic hyaluronic acid modified with catechol group (HADA). The resulting TMBG/QCS/HADA based hemostatic powder (TMQH) rapidly absorbs plasma, concentrating blood coagulation factors. Simultaneously, the water-soluble QCS and HADA interact to form a 3D network structure, which can be strengthened by crosslinking with TMBG. This network effectively captures clustered blood coagulation factors, leading to a strong and adhesive thrombus that resists disruption from blood flow. TMQH exhibits superior efficacy in promoting hemostasis compared to Celox™ both in rat arterial injuries and non-compressible liver puncture wounds. TMQH demonstrates excellent antibacterial activity, cytocompatibility, and blood compatibility. These outstanding superiorities in blood clotting capability, wet tissue adhesion, antibacterial activity, safety for living organisms, ease of application, and long-term stability, make TMQH highly suitable for emergency hemostasis.


Blood Coagulation , Hemostatics , Powders , Tannins , Animals , Rats , Blood Coagulation/drug effects , Tannins/chemistry , Tannins/pharmacology , Hemostatics/chemistry , Hemostatics/pharmacology , Porosity , Glass/chemistry , Polysaccharides/chemistry , Polysaccharides/pharmacology , Chitosan/chemistry , Chitosan/pharmacology , Gels/chemistry , Humans , Adhesives/chemistry , Adhesives/pharmacology , Male , Rats, Sprague-Dawley , Hemostasis/drug effects , Biocompatible Materials/chemistry , Biocompatible Materials/pharmacology
7.
Biomacromolecules ; 25(6): 3335-3344, 2024 Jun 10.
Article En | MEDLINE | ID: mdl-38717974

Hemostatic powder is widely employed for emergency bleeding control due to its ability to conform to irregularly shaped wounds, ease of use, and stable storage. However, current powders exhibit limited tissue adhesion and insufficient support for thrombus formation, making them easily washed away by blood. In this study, a hybrid powder (QAL) was produced by mixing quaternized chitosan (QCS) powder, catechol-modified alginate (Cat-SA) powder, and laponite (Lap) powder. Upon addition of QAL, the blood quickly transformed to a robust and adhesive blood gel. The adhesion strength of the blood gel was up to 31.33 ± 1.56 kPa. When compared with Celox, QAL showed superior performance in promoting hemostasis. Additionally, QAL exhibited effectiveness in eliminating bacteria while also demonstrating outstanding biocompatibility with cells and blood. These favorable properties, including strong coagulation, adhesion to wet tissue, antibacterial activity, biosafety, ease of use, and stable storage, make QAL a promising emergency hemostatic agent.


Alginates , Blood Coagulation , Chitosan , Hemostatics , Powders , Silicates , Hemostatics/chemistry , Hemostatics/pharmacology , Silicates/chemistry , Animals , Blood Coagulation/drug effects , Powders/chemistry , Chitosan/chemistry , Alginates/chemistry , Alginates/pharmacology , Humans , Mice , Gels/chemistry , Polysaccharides/chemistry , Polysaccharides/pharmacology , Hemostasis/drug effects
8.
Colloids Surf B Biointerfaces ; 239: 113927, 2024 Jul.
Article En | MEDLINE | ID: mdl-38714078

Humans often have bleeding, which exerts substantial selective pressure on the coagulation system to optimize hemostasis in a variety of situations. Uncontrolled hemorrhage due to severe trauma leads to morbidity and mortality. Although nonbiological surfaces such as silicates can activate coagulation factor XII (FXII), the presence of Zn (Zinc) in the material stimulates and activates the various steps in the coagulation cascade. This results in blood clotting. The Zn@SiO2 nanocomposite has an excellent hemostatic property that establishes hemostasis by activating the factors responsible for the formation of a stable clot called fibrin mesh. This can be used as a hemostatic agent during surgeries and in any other trauma condition related to bleeding. Zn@SiO2 was synthesized and characterized with XRD, FTIR and HRTEM. It is analyzed for its RBC (Red Blood Corpuscles) aggregation and Platelet adhesion ability, fibrin formation, thrombus formation and prothrombin time (PT), Activated Partial Thromboplastin Time (aPTT), D-dimer for its ability to activate the coagulation cascade to achieve stable clotting.


Blood Coagulation , Nanocomposites , Silicon Dioxide , Zinc , Nanocomposites/chemistry , Blood Coagulation/drug effects , Zinc/chemistry , Zinc/pharmacology , Silicon Dioxide/chemistry , Humans , Partial Thromboplastin Time , Prothrombin Time , Platelet Adhesiveness/drug effects , Animals , Particle Size , Fibrin Fibrinogen Degradation Products/metabolism , Hemostatics/chemistry , Hemostatics/pharmacology
9.
Biomed Mater ; 19(4)2024 Jun 07.
Article En | MEDLINE | ID: mdl-38815608

The development of a composite sponge with high water absorbency and active coagulation mechanism for traumatic hemostasis and anti-infection remains a challenge. Herein, we developed a composite sponge using gelation, swelling, and freeze-drying methods based on quaternized chitosan, succinimidyl-modified F127, and bioactive glass. The sponge exhibited macroporous structure, high porosity, and water absorbency. When exposed to blood, it strongly interacted with blood cells, promoting their adhesion, aggregation, and activation. Moreover, it activated the intrinsic coagulation pathway. The sponge/powder demonstrated superior hemostatic capacity to commercial gauze, gelatin sponge, Yunnan Baiyao, and chitosan hemostatic powder in rat tail amputation, liver superficial injury, liver resection, and liver semi-perforation wound models. The sponge also presented robust anti-infection activity against methicillin-resistantStaphylococcus aureusandEscherichia coli. Additionally, the sponge showed low cytotoxicity, hemolysis activity, inflammation response, and systemic toxicity, demonstrating its favorable biocompatibility.


Blood Coagulation , Chitosan , Hemostasis , Hemostatics , Rats, Sprague-Dawley , Animals , Rats , Porosity , Chitosan/chemistry , Hemostasis/drug effects , Blood Coagulation/drug effects , Hemostatics/chemistry , Hemostatics/pharmacology , Male , Water/chemistry , Biocompatible Materials/chemistry , Biocompatible Materials/pharmacology , Escherichia coli/drug effects , Anti-Infective Agents/pharmacology , Anti-Infective Agents/chemistry , Liver/injuries , Humans , Methicillin-Resistant Staphylococcus aureus/drug effects , Materials Testing , Wounds and Injuries
10.
J Mater Chem B ; 12(22): 5439-5454, 2024 Jun 05.
Article En | MEDLINE | ID: mdl-38726947

Powder-based hemostatic technology has offered unprecedented opportunities in surgical sealing and repair of irregularly shaped and noncompressible wounds. Despite their routine use, existing clinical hemostatic powders are challenged either by poor mechanical properties or inadequate adhesion to bleeding tissues in biological environments. Here, inspired by the mussel foot proteins' fusion assembly strategy, a novel silk fibroin-based hemostatic powder (named as SF/PEG/TA) with instant and robust adhesion performance is developed. Upon absorbing interfacial liquids, the SF/PEG/TA powders rapidly swell into micro-gels and subsequently contact with each other to transform into a macroscopically homogeneous hydrogel in situ, strengthening its interfacial bonding with various substrates in fluidic environments. The in vitro and in vivo results show that the SF/PEG/TA powder possesses ease of use, good biocompatibility, strong antibacterial activities, and effective blood clotting abilities. The superior hemostatic sealing capability of the SF/PEG/TA powder is demonstrated in the rat liver, heart, and gastrointestinal injury models. Moreover, in vivo investigation of rat skin incision and gastrointestinal perforation models validates that the SF/PEG/TA powder promotes wound healing and tissue regeneration. Taken together, compared to existing clinical hemostatic powders, the proposed SF/PEG/TA powder with superior wound treatment capabilities has high potential for clinical hemostasis and emergency rescue.


Fibroins , Hemostatics , Powders , Rats, Sprague-Dawley , Fibroins/chemistry , Fibroins/pharmacology , Animals , Hemostatics/chemistry , Hemostatics/pharmacology , Rats , Wound Healing/drug effects , Male , Biocompatible Materials/chemistry , Biocompatible Materials/pharmacology , Humans , Polyethylene Glycols/chemistry
11.
Int J Biol Macromol ; 270(Pt 2): 132174, 2024 Jun.
Article En | MEDLINE | ID: mdl-38750842

Hydrogels containing catechol group have received attention in the biomedical field due to their robust adhesive/cohesive capabilities, biocompatibility, and hemostatic abilities. Catechol-functionalized chitosan holds promise for preparing self-assembly hydrogels. However, issues of inefficient gelation and instability still persist in these hydrogels. In the current study, we synthesized chitosan catechol (CC) of high catechol substitution (∼28 %) and combined CC with tannic acid (TA, which also contains catechol) to form self-healing CC-TA hydrogels. The catechol-enriched CC-TA composite hydrogels showed rapid gelation and mechanical reinforcement (shear modulus ∼110 Pa). In situ coherent small-angle X-ray scattering (SAXS) coupled with rheometry revealed a morphological feature of mesoscale clusters (∼20 nm) within CC-TA hydrogel. The clusters underwent dynamic destruction under large-amplitude oscillatory shear, corresponding with the strain-dependent and self-healing behavior of the CC-TA hydrogel. The composite hydrogel had osmotic-responsive and notable adhesive properties. Meanwhile, CC-TA composite cryogel prepared simply through freeze-thawing procedures exhibited distinctive macroporous structure (∼200 µm), high water swelling ratio (∼7000 %), and favorable compressive modulus (∼8 kPa). The sponge-like cryogel was fabricated into swabs, demonstrating hemostatic capacity. The CC-TA composites, in both hydrogel and cryogel forms, possessed ROS scavenging ability, antimicrobial activity, and cell compatibility with potentials in biological applications.


Catechols , Chitosan , Cryogels , Hemostatics , Hydrogels , Tannins , Chitosan/chemistry , Chitosan/pharmacology , Catechols/chemistry , Catechols/pharmacology , Tannins/chemistry , Tannins/pharmacology , Cryogels/chemistry , Hydrogels/chemistry , Hydrogels/pharmacology , Hemostatics/chemistry , Hemostatics/pharmacology , Anti-Infective Agents/pharmacology , Anti-Infective Agents/chemistry , Animals , Rheology
12.
Carbohydr Polym ; 336: 122111, 2024 Jul 15.
Article En | MEDLINE | ID: mdl-38670748

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.


Anti-Bacterial Agents , Chitosan , Hemostatics , Polyphenols , Staphylococcus aureus , Starch , Tannins , Tannins/chemistry , Tannins/pharmacology , Chitosan/chemistry , Chitosan/pharmacology , Starch/chemistry , Starch/pharmacology , Animals , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Hemostatics/chemistry , Hemostatics/pharmacology , Mice , Rats , Staphylococcus aureus/drug effects , Hemostasis/drug effects , Escherichia coli/drug effects , Male , Hemolysis/drug effects , Humans , Erythrocytes/drug effects
13.
Carbohydr Polym ; 336: 122125, 2024 Jul 15.
Article En | MEDLINE | ID: mdl-38670756

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.


Anti-Bacterial Agents , Chitosan , Chitosan/analogs & derivatives , Escherichia coli , Hemostasis , Hydrogels , Protamines , Skin , Staphylococcus aureus , Wound Healing , Chitosan/chemistry , Chitosan/pharmacology , Wound Healing/drug effects , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Hydrogels/chemistry , Hydrogels/pharmacology , Animals , Escherichia coli/drug effects , Staphylococcus aureus/drug effects , Protamines/chemistry , Protamines/pharmacology , Hemostasis/drug effects , Skin/drug effects , Mice , Male , Rats , Hemostatics/pharmacology , Hemostatics/chemistry , Tissue Adhesives/pharmacology , Tissue Adhesives/chemistry
14.
Mar Drugs ; 22(4)2024 Apr 20.
Article En | MEDLINE | ID: mdl-38667805

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.


Blood Coagulation , Edible Seaweeds , Hemostatics , Hydrogels , Laminaria , Polysaccharides , Hydrogels/chemistry , Hydrogels/pharmacology , Laminaria/chemistry , Polysaccharides/chemistry , Polysaccharides/pharmacology , Polysaccharides/isolation & purification , Blood Coagulation/drug effects , Hemostatics/pharmacology , Hemostatics/chemistry , Hemostatics/isolation & purification , Humans , Animals , Chitosan/chemistry , Chitosan/pharmacology , Polyvinyl Alcohol/chemistry , Hemostasis/drug effects , Hemolysis/drug effects
15.
Molecules ; 29(8)2024 Apr 21.
Article En | MEDLINE | ID: mdl-38675708

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.


Anti-Bacterial Agents , Escherichia coli , Hemostasis , Hemostatics , Nanoparticles , Plant Extracts , Silicon Dioxide , Staphylococcus aureus , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Silicon Dioxide/chemistry , Nanoparticles/chemistry , Escherichia coli/drug effects , Hemostasis/drug effects , Staphylococcus aureus/drug effects , Hemostatics/chemistry , Hemostatics/pharmacology , Porosity , Animals , Hemolysis/drug effects , Blood Coagulation/drug effects , Humans , Dracaena/chemistry , Mice , Microbial Sensitivity Tests
16.
Int J Biol Macromol ; 266(Pt 1): 131399, 2024 May.
Article En | MEDLINE | ID: mdl-38641504

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.


Alginates , Chitosan , Chitosan/analogs & derivatives , Cryogels , Hemorrhage , Hemostasis , Hemostatics , Chitosan/chemistry , Cryogels/chemistry , Alginates/chemistry , Animals , Hemorrhage/drug therapy , Rats , Hemostasis/drug effects , Hemostatics/chemistry , Hemostatics/pharmacology , Biocompatible Materials/chemistry , Humans , Male
17.
J Mater Chem B ; 12(17): 4172-4183, 2024 May 01.
Article En | MEDLINE | ID: mdl-38591253

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.


Decapodiformes , Hemostatics , Ink , Nanoparticles , Animals , Rats , Hemostatics/chemistry , Hemostatics/pharmacology , Nanoparticles/chemistry , Decapodiformes/chemistry , Hemorrhage/drug therapy , Male , Blood Coagulation/drug effects , Rats, Sprague-Dawley , Humans , Biocompatible Materials/chemistry , Biocompatible Materials/pharmacology , Hemostasis/drug effects , Bone and Bones/drug effects , Particle Size
18.
ACS Appl Mater Interfaces ; 16(17): 21472-21485, 2024 May 01.
Article En | MEDLINE | ID: mdl-38626344

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.


Anti-Bacterial Agents , Hydrogels , Wound Healing , Wound Healing/drug effects , Hydrogels/chemistry , Hydrogels/pharmacology , Animals , Mice , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Hemostatics/chemistry , Hemostatics/pharmacology , Bandages , Adhesives/chemistry , Adhesives/pharmacology , Escherichia coli/drug effects , Staphylococcus aureus/drug effects , Hemostasis/drug effects , Polymers/chemistry , Polymers/pharmacology
19.
ACS Appl Mater Interfaces ; 16(17): 21582-21594, 2024 May 01.
Article En | MEDLINE | ID: mdl-38634578

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.


Anti-Bacterial Agents , Emulsions , Fibroins , Fluorocarbons , Hydrogels , Staphylococcus aureus , Fluorocarbons/chemistry , Fluorocarbons/pharmacology , Hydrogels/chemistry , Hydrogels/pharmacology , Animals , Emulsions/chemistry , Emulsions/pharmacology , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Staphylococcus aureus/drug effects , Fibroins/chemistry , Fibroins/pharmacology , Mice , Hemostatics/chemistry , Hemostatics/pharmacology , Nanoparticles/chemistry , Staphylococcal Infections/drug therapy , Ultrasonic Waves , Male , Rats , Humans
20.
Int J Biol Macromol ; 269(Pt 1): 131772, 2024 Jun.
Article En | MEDLINE | ID: mdl-38670176

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.


Biocompatible Materials , Hemostasis , Hemostatics , Hemostatics/chemistry , Hemostatics/pharmacology , Hemostatics/therapeutic use , Humans , Hemostasis/drug effects , Biocompatible Materials/chemistry , Animals , Polymers/chemistry , Hemorrhage/drug therapy
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