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1.
Nat Commun ; 15(1): 5557, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38956415

RESUMO

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.


Assuntos
DNA , Armadilhas Extracelulares , Hemostasia , Hemostáticos , Hidrogéis , Cicatrização , Animais , Armadilhas Extracelulares/metabolismo , Armadilhas Extracelulares/efeitos dos fármacos , DNA/química , Masculino , Hidrogéis/química , Hidrogéis/farmacologia , Ratos , Hemostasia/efeitos dos fármacos , Cicatrização/efeitos dos fármacos , Hemostáticos/farmacologia , Hemostáticos/química , Ratos Sprague-Dawley , Hemorragia , Humanos , Neutrófilos/metabolismo , Modelos Animais de Doenças
2.
ACS Appl Mater Interfaces ; 16(27): 34783-34797, 2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-38949260

RESUMO

Trauma is the leading cause of death for adults under the age of 44. Internal bleeding remains a significant challenge in medical emergencies, necessitating the development of effective hemostatic materials that could be administered by paramedics before a patient is in the hospital and treated by surgeons. In this study, we introduce a graphene oxide (GO)-based PEGylated synthetic hemostatic nanomaterial with an average size of 211 ± 83 nm designed to target internal bleeding by mimicking the role of fibrinogen. Functionalization of GO-g-PEG with peptides derived from the α-chain of fibrinogen, such as GRGDS, or the γ-chain of fibrinogen, such as HHLGGAKQAGDV:H12, was achieved with peptide loadings of 72 ± 6 and 68 ± 15 µM, respectively. In vitro studies with platelet-rich plasma (PRP) under confinement demonstrated aggregation enhancement of 39 and 24% for GO-g-PEG-GRGDS and GO-g-PEG-H12, respectively, compared to buffer, while adenosine diphosphate (ADP) alone induced a 5% aggregation. Compared to the same materials in the absence of ADP, GO-g-PEG-GRGDS achieved a 47% aggregation enhancement, while GO-g-PEG-H12 a 25% enhancement. This is particularly important for injectable hemostats and highlights the fact that our nanographene-based materials can only act as hemostats in the presence of agonists, reducing the possibility of unwanted clotting during circulation. Further studies on collagen-coated wells under dynamic flow revealed statistically significant augmentation of PRP fluorescence signal using GRGDS- or H12-coated GO-g-PEG compared to controls. Hemolysis studies showed <1% lysis of red blood cells (RBCs) at the highest PEGylated nanographene concentration. Finally, whole human blood coagulation studies reveal faster and more pronounced clotting using our nanohemostats vs PBS control from 3 min and below (blood is clotted with 10% CaCl2 within 4-5 min), with the biggest differences to be shown at 2 and 1 min. At 1 min, the clot weight was found to be ∼45% of that between 4 and 5 min, while no clot was formed in PBS-treated blood. Reduction of CaCl2 to 5 and 3%, or utilization of prostaglandin E1, an anticoagulant, still leads to clots but of smaller weight. The findings highlight the potential of our fibrinogen-mimic PEGylated nanographene as a promising non-hemolytic injectable scaffold for targeting internal bleeding, offering insights into its platelet aggregation capabilities under confinement and under dynamic flow as well as its pronounced coagulation abilities.


Assuntos
Fibrinogênio , Grafite , Hemostáticos , Grafite/química , Hemostáticos/química , Hemostáticos/farmacologia , Humanos , Fibrinogênio/química , Fibrinogênio/metabolismo , Polietilenoglicóis/química , Coagulação Sanguínea/efeitos dos fármacos , Materiais Biomiméticos/química , Materiais Biomiméticos/farmacologia , Hemorragia/tratamento farmacológico
3.
Sci Rep ; 14(1): 16139, 2024 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-38997417

RESUMO

Rapid and safe hemostasis is crucial for the survival of bleeding patients in prehospital care. It is urgent to develop high performance hemostatic material to control the massive hemorrhage in the military field and accidental trauma. In this work, an efficient protein hemostat of thrombin was immobilized onto commercial gauze, which was mediated by self-polymerization and anchoring of tannic acid (TA). Through TA treatment, the efficient immobilization of thrombin was achieved, preserving both the biological activity of thrombin and the physical properties of the dressing, including absorbency, breathability, and mechanical performance. Moreover, in the presence of TA coating and thrombin, Gau@TA/Thr could obviously shortened clotting time and enriched blood components such as plasma proteins, platelets, and red blood cells, thereby exhibiting an enhanced in vitro coagulation effect. In SD rat liver volume defect and artery transection hemorrhage models, Gau@TA/Thr still had outstanding hemostatic performance. Besides, the Gau@TA/Thr gauze had inherent antibacterial property and demonstrated excellent biocompatibility. All results suggested that Gau@TA/Thr would be a potential candidate for treating uncontrollable hemorrhage in prehospital care.


Assuntos
Bandagens , Coagulação Sanguínea , Hemorragia , Hemostáticos , Taninos , Trombina , Taninos/química , Taninos/farmacologia , Animais , Hemorragia/tratamento farmacológico , Trombina/metabolismo , Coagulação Sanguínea/efeitos dos fármacos , Ratos , Hemostáticos/farmacologia , Hemostáticos/química , Ratos Sprague-Dawley , Masculino , Anti-Infecciosos/farmacologia , Humanos , Proteínas Imobilizadas/farmacologia , Proteínas Imobilizadas/química , Modelos Animais de Doenças , Polifenóis
4.
Molecules ; 29(13)2024 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-38998951

RESUMO

In our search for a biocompatible composite hemostatic dressing, we focused on the design of a novel biomaterial composed of two natural biological components, collagen and sodium alginate (SA), cross-linked using 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide/N-hydroxysuccinimide (EDC/NHS) and oxidized sodium alginate (OSA). We conducted a series of tests to evaluate the physicochemical properties, acute systemic toxicity, skin irritation, intradermal reaction, sensitization, cytotoxicity, and in vivo femoral artery hemorrhage model. The results demonstrated the excellent biocompatibility of the collagen/sodium alginate (C/SA)-based dressings before and after crosslinking. Specifically, the femoral artery hemorrhage model revealed a significantly shortened hemostasis time of 132.5 ± 12.82 s for the EDC/NHS cross-linked dressings compared to the gauze in the blank group (hemostasis time of 251.43 ± 10.69 s). These findings indicated that C/SA-based dressings exhibited both good biocompatibility and a significant hemostatic effect, making them suitable for biomedical applications.


Assuntos
Alginatos , Bandagens , Colágeno , Hemostáticos , Alginatos/química , Alginatos/farmacologia , Animais , Colágeno/química , Colágeno/farmacologia , Hemostáticos/química , Hemostáticos/farmacologia , Camundongos , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Teste de Materiais , Hemorragia/tratamento farmacológico , Masculino , Ratos , Hemostasia/efeitos dos fármacos , Artéria Femoral
5.
Nutrients ; 16(13)2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38999733

RESUMO

Natural and synthetic colorants present in food can modulate hemostasis, which includes the coagulation process and blood platelet activation. Some colorants have cardioprotective activity as well. However, the effect of genipin (a natural blue colorant) and synthetic blue colorants (including patent blue V and brilliant blue FCF) on hemostasis is not clear. In this study, we aimed to investigate the effects of three blue colorants-genipin, patent blue V, and brilliant blue FCF-on selected parameters of hemostasis in vitro. The anti- or pro-coagulant potential was assessed in human plasma by measuring the following coagulation times: thrombin time (TT), prothrombin time (PT), and activated partial thromboplastin time (APTT). Moreover, we used the Total Thrombus formation Analysis System (T-TAS, PL-chip) to evaluate the anti-platelet potential of the colorants in whole blood. We also measured their effect on the adhesion of washed blood platelets to fibrinogen and collagen. Lastly, the cytotoxicity of the colorants against blood platelets was assessed based on the activity of extracellular lactate dehydrogenase (LDH). We observed that genipin (at all concentrations (1-200 µM)) did not have a significant effect on the coagulation times (PT, APTT, and TT). However, genipin at the highest concentration (200 µM) and patent blue V at the concentrations of 1 and 10 µM significantly prolonged the time of occlusion measured using the T-TAS, which demonstrated their anti-platelet activity. We also observed that genipin decreased the adhesion of platelets to fibrinogen and collagen. Only patent blue V and brilliant blue FCF significantly shortened the APTT (at the concentration of 10 µM) and TT (at concentrations of 1 and 10 µM), demonstrating pro-coagulant activity. These synthetic blue colorants also modulated the process of human blood platelet adhesion, stimulating the adhesion to fibrinogen and inhibiting the adhesion to collagen. The results demonstrate that genipin is not toxic. In addition, because of its ability to reduce blood platelet activation, genipin holds promise as a novel and valuable agent that improves the health of the cardiovascular system and reduces the risk of cardiovascular diseases. However, the mechanism of its anti-platelet activity remains unclear and requires further studies. Its in vivo activity and interaction with various anti-coagulant and anti-thrombotic drugs, including aspirin and its derivatives, should be examined as well.


Assuntos
Coagulação Sanguínea , Plaquetas , Corantes de Alimentos , Iridoides , Humanos , Iridoides/farmacologia , Coagulação Sanguínea/efeitos dos fármacos , Corantes de Alimentos/farmacologia , Plaquetas/efeitos dos fármacos , Plaquetas/metabolismo , Hemostasia/efeitos dos fármacos , Tempo de Tromboplastina Parcial , Adesividade Plaquetária/efeitos dos fármacos , Fibrinogênio/metabolismo , Benzenossulfonatos/farmacologia , Tempo de Protrombina , Corantes de Rosanilina/farmacologia , Hemostáticos/farmacologia , Ativação Plaquetária/efeitos dos fármacos , Tempo de Trombina
6.
Med Sci Monit ; 30: e943353, 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38825814

RESUMO

BACKGROUND Dentin contamination with hemostatic agents before bonding indirect restorations negatively affects the bond strength. However, the consensus on which materials could be used to clean contamination of hemostatic agents has not been explored. The aim of this study was to assess the effect of Katana Cleaner applied on the surface of dentin contaminated with hemostatic agents on the shear bond strength (SBS) of self-adhesive resin cement by comparing it with three other surface cleaners. MATERIAL AND METHODS Ninety dentin specimens were divided into a no contamination group (control) (n=10), 4 groups contaminated with 25% aluminum chloride (Viscostat Clear) (n=40), and 4 groups contaminated with 20% ferric sulfate (Viscostat) (n=40). Subsequently, 4 different cleaners were used for each contamination group (water rinse, phosphoric acid, chlorhexidine, and Katana Cleaner). Then, self-adhesive resin cement was directly bonded to the treated surfaces. All specimens were subjected to 5000 thermal cycles of artificial aging. The shear bond strength was measured using a universal testing machine. RESULTS Two-way analysis of variance showed that the contaminant type as the main factor was statistically non-significant (p=0.655), cleaner type as the main factor was highly significant (p<0.001), and interaction between the contaminant and cleaner was non-significant (p=0.51). The cleaner type was the main factor influencing the bond strength. Phosphoric acid and chlorhexidine showed better performance than Katana Cleaner. CONCLUSIONS Cleaning dentin surface contamination with phosphoric acid and chlorhexidine had better performance than with Katana Cleaner.


Assuntos
Colagem Dentária , Dentina , Hemostáticos , Cimentos de Resina , Resistência ao Cisalhamento , Humanos , Dentina/efeitos dos fármacos , Hemostáticos/farmacologia , Colagem Dentária/métodos , Clorexidina/análogos & derivados , Clorexidina/farmacologia , Teste de Materiais/métodos , Propriedades de Superfície/efeitos dos fármacos , Adesivos Dentinários , Compostos Férricos/química
7.
Sci Rep ; 14(1): 12800, 2024 06 04.
Artigo em Inglês | MEDLINE | ID: mdl-38834591

RESUMO

This study aims to observe the hemostatic and anti-inflammatory effects of intravenous administration of tranexamic acid (TXA) in dual segment posterior lumbar interbody fusion (PLIF). The data of 53 patients with lumbar disease treated with double-segment PLIF were included in this study. The observation group was received a single-dose intravenous of TXA (1 g/100 mL) 15 min before skin incision after general anesthesia. The control group was not received TXA. The observation indicators included postoperative activated partial prothrombin time (APTT), thrombin time (PT), thrombin time (TT), fibrinogen (FIB), platelets (PLT), and postoperative deep vein thrombosis in the lower limbs, surgical time, intraoperative bleeding volume, postoperative drainage volume, transfusion rate, postoperative hospital stay, red blood cell (RBC), hemoglobin (HB), hematocrit (HCT), C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) on the 1st, 4th, 7th, and last tested day after surgery. All patients successfully completed the operation, and there was no deep vein thrombosis after operation. There was no statistically significant difference in postoperative APTT, PT, TT, FIB, PLT, surgical time, and postoperative hospital stay between the two groups (p > 0.05). The intraoperative bleeding volume, postoperative drainage volume, and transfusion rate in the observation group were lower than those in the control group, and the differences were statistically significant (p < 0.05). There was no statistically significant difference in RBC, HB, HCT, CRP, and ESR between the two groups on the 1st, 4th, 7th, and last tested day after surgery (p > 0.05). Intravenous administration of TXA in dual segment PLIF does not affect coagulation function and can reduce bleeding volume, postoperative drainage volume, and transfusion rate. Moreover, it does not affect the postoperative inflammatory response.


Assuntos
Fusão Vertebral , Ácido Tranexâmico , Humanos , Ácido Tranexâmico/administração & dosagem , Feminino , Masculino , Pessoa de Meia-Idade , Fusão Vertebral/métodos , Fusão Vertebral/efeitos adversos , Estudos de Casos e Controles , Idoso , Vértebras Lombares/cirurgia , Administração Intravenosa , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/farmacologia , Hemostáticos/administração & dosagem , Hemostáticos/farmacologia , Adulto , Perda Sanguínea Cirúrgica/prevenção & controle , Antifibrinolíticos/administração & dosagem , Antifibrinolíticos/uso terapêutico
8.
Sci Rep ; 14(1): 13941, 2024 06 17.
Artigo em Inglês | MEDLINE | ID: mdl-38886391

RESUMO

The present study focused on evaluating the antibacterial properties, radical scavenging, and photocatalytic activities of Centaurea behen-mediated silver nanoparticles (Cb-AgNPs). The formation of Cb-AgNPs was approved by UV-Vis spectrometry, Fourier-transform infrared spectroscopy, transmission electron microscopy, scanning electron microscopy (SEM), energy dispersive X-ray and X-ray diffraction. The results showed that the obtained AgNPs have a maximum absorbance peak at 450 nm with spherical morphology and an average size of 13.03 ± 5.8 nm. The catalytic activity of the Cb-AgNPs was investigated using Safranin O (SO) solution as a cationic dye model. The Cb-AgNPs performed well in the removal of SO. The coupled physical adsorption/photocatalysis reaction calculated about 68% and 98% degradation of SO dye under solar irradiation. The Cb-AgNPs inhibited the growth of gram-negative or positive bacteria strains and had excellent DPPH radicals scavenging ability (100% in a concentration of 200 µg/ml) as well as a good effect on reducing coagulation time (at concentrations of 200 and 500 µg/mL reduced clotting time up to 3 min). Considering the fact that green synthesized Cb-AgNPs have antioxidant and antibacterial properties and have a good ability to reduce coagulation time, they can be used in wound dressings. As well as these NPs with good photocatalytic activity can be a suitable option for degrading organic pollutants.


Assuntos
Antibacterianos , Centaurea , Química Verde , Nanopartículas Metálicas , Extratos Vegetais , Folhas de Planta , Prata , Prata/química , Prata/farmacologia , Nanopartículas Metálicas/química , Antibacterianos/farmacologia , Antibacterianos/química , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Folhas de Planta/química , Química Verde/métodos , Centaurea/química , Poluentes Ambientais/química , Hemostáticos/farmacologia , Hemostáticos/química , Testes de Sensibilidade Microbiana
9.
Biomed Mater ; 19(4)2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38838692

RESUMO

At present, wound dressings in clinical applications are primarily used for superficial skin wounds. However, these dressings have significant limitations, including poor biocompatibility and limited ability to promote wound healing. To address the issue, this study used aldehyde polyethylene glycol as the cross-linking agent to design a carboxymethyl chitosan-methacrylic acid gelatin hydrogel with enhanced biocompatibility, which can promote wound healing and angiogenesis. The CSDG hydrogel exhibits acid sensitivity, with a swelling ratio of up to 300%. Additionally, it exhibited excellent resistance to external stress, withstanding pressures of up to 160 kPa and self-deformation of 80%. Compared to commercially available chitosan wound gels, the CSDG hydrogel demonstrates excellent biocompatibility, antibacterial properties, and hemostatic ability. Bothin vitroandin vivoresults showed that the CSDG hydrogel accelerated blood vessel regeneration by upregulating the expression of CD31, IL-6, FGF, and VEGF, thereby promoting rapid healing of wounds. In conclusion, this study successfully prepared the CSDG hydrogel wound dressings, providing a new approach and method for the development of hydrogel dressings based on natural macromolecules.


Assuntos
Materiais Biocompatíveis , Quitosana , Gelatina , Hidrogéis , Metacrilatos , Cicatrização , Quitosana/química , Quitosana/análogos & derivados , Cicatrização/efeitos dos fármacos , Gelatina/química , Hidrogéis/química , Animais , Metacrilatos/química , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Camundongos , Humanos , Polietilenoglicóis/química , Antibacterianos/química , Antibacterianos/farmacologia , Neovascularização Fisiológica/efeitos dos fármacos , Bandagens , Masculino , Reagentes de Ligações Cruzadas/química , Regeneração/efeitos dos fármacos , Hemostáticos/química , Hemostáticos/farmacologia , Teste de Materiais , Ratos
10.
Int J Biol Macromol ; 272(Pt 2): 132930, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38848843

RESUMO

The rapid absorption of water from the blood to concentrate erythrocytes and platelets, thus triggering quick closure, is important for hemostasis. Herein, expansion-clotting chitosan fabrics are designed and fabricated by ring spinning of polylactic acid (PLA) filaments as the core layer and highly hydrophilic carboxyethyl chitosan (CECS) fibers as the sheath layer, and subsequent knitting of obtained PLA@CECS core spun yarns. Due to the unidirectional fast-absorption capacity of CECS fibers, the chitosan fabrics can achieve erythrocytes and platelets aggregate quickly by concentrating blood, thus promoting the formation of blood clots. Furthermore, the loop structure of coils formed in the knitted fabric can help them to expand by absorbing water to close their pores, providing effective sealing for bleeding. Besides, They have enough mechanical properties, anti-penetrating ability, and good tissue-adhesion ability in wet conditions, which can form a physical barrier to resist blood pressure during hemostasis and prevent them from falling off the wound, thus enhancing hemostasis synergistically. Therefore, the fabrics exhibit superior hemostatic performance in the rabbit liver, spleen, and femoral artery puncture injury model compared to the gauze group. This chitosan fabric is a promising hemostatic material for hemorrhage control.


Assuntos
Quitosana , Hemorragia , Hemostáticos , Quitosana/química , Animais , Hemorragia/tratamento farmacológico , Hemorragia/prevenção & controle , Coelhos , Hemostáticos/química , Hemostáticos/farmacologia , Poliésteres/química , Têxteis , Coagulação Sanguínea/efeitos dos fármacos , Hemostasia/efeitos dos fármacos
11.
Nat Commun ; 15(1): 5460, 2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38937462

RESUMO

Developing superporous hemostatic sponges with simultaneously enhanced permeability and mechanical properties remains challenging but highly desirable to achieve rapid hemostasis for non-compressible hemorrhage. Typical approaches to improve the permeability of hemostatic sponges by increasing porosity sacrifice mechanical properties and yield limited pore interconnectivity, thereby undermining the hemostatic efficacy and subsequent tissue regeneration. Herein, we propose a temperature-assisted secondary network compaction strategy following the phase separation-induced primary compaction to fabricate the superporous chitosan sponge with highly-interconnected porous structure, enhanced blood absorption rate and capacity, and fatigue resistance. The superporous chitosan sponge exhibits rapid shape recovery after absorbing blood and maintains sufficient pressure on wounds to build a robust physical barrier to greatly improve hemostatic efficiency. Furthermore, the superporous chitosan sponge outperforms commercial gauze, gelatin sponges, and chitosan powder by enhancing hemostatic efficiency, cell infiltration, vascular regeneration, and in-situ tissue regeneration in non-compressible organ injury models, respectively. We believe the proposed secondary network compaction strategy provides a simple yet effective method to fabricate superporous hemostatic sponges for diverse clinical applications.


Assuntos
Quitosana , Hemostasia , Hemostáticos , Permeabilidade , Animais , Porosidade , Quitosana/química , Hemostáticos/química , Hemostáticos/farmacologia , Suínos , Hemostasia/fisiologia , Hemorragia/terapia , Masculino
12.
Int J Biol Macromol ; 273(Pt 1): 133075, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38866274

RESUMO

Hemostatic materials play a crucial role in trauma medicine. However, existing materials have poor hemostatic efficacy and a tendency to adhere to the wound surface, limiting their clinical effectiveness. Herein, a drug-loaded, superhydrophilic/superhydrophobic laminated material (DSLM), consisting of a superhydrophobic inner layer with a micropore array, a superhydrophilic chitosan-based sponge layer loaded with hemostatic/antimicrobial drugs, and a superhydrophobic outer layer, was developed. Furthermore, the DSLM allows unidirectional flow of blood and exudates from the wound bed through the superhydrophobic inner layer while facilitating efficient drug delivery. In addition, it possesses excellent biocompatibility and antiadhesion properties, as confirmed by in vivo and in vitro experiments. Compared with traditional hemostatic materials, the DSLM remarkably increased the survival time by over threefold in the acute femoral transaction wound bleeding model, and simultaneously prevented secondary wound damage by reducing peeling force to one-eighth incomparison to pristine gauze. The DSLM holds promise as a versatile clinical biomaterial for prehospital acute trauma treatment, with its simple structure facilitating manufacturing and expanding applications in biomedicine.


Assuntos
Quitosana , Hemostasia , Hemostáticos , Interações Hidrofóbicas e Hidrofílicas , Quitosana/química , Hemostasia/efeitos dos fármacos , Animais , Hemostáticos/química , Hemostáticos/farmacologia , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Hemorragia/tratamento farmacológico , Hemorragia/prevenção & controle , Ratos , Camundongos , Cicatrização/efeitos dos fármacos , Masculino , Humanos
13.
Biomater Adv ; 162: 213932, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38917648

RESUMO

Clay minerals have attracted wide attention as biomedical materials due to the unique crystal structure, abundant morphology and good biocompatibility. However, the relevant studies on the abundant natural mixed clay deposits were scarcely reported. Herein, the hemostatic performance of natural mixed-dimensional attapulgite clay (MDAPT) composed of one-dimensional attapulgite and multiple two-dimensional clay were systematically investigated based on the structural evolution using oxalic acid for different time. The results of hemostatic evaluation showed that MDAPT leached by oxalic acid with 1 h presented the shortest clotting time (134 ± 12.17 s), a 15.09 % and 41.74 % reduction of relative hemoglobin absorbance at 180 s and 120 s when compared with the control group, respectively, and an increase of 19.45 % of the blood clotting index in vitro, as well as MDAPT obtained the shortest bleeding time (158.5 ± 6.9 s), nearly 66 % and 31 % reduction blood loss as compared to the blank group and the YNBY group in vivo. This improvement was primarily ascribed to the synergistic effect of lamellar non-expandable illite, and nano rod-like attapulgite. Furthermore, the rapid hemostasis of MDAPT was also due to the joint effect of superhydrophobic property toward blood, minimizing blood loss, surface negative charge, metal ions from MDAPT structural skeleton, promoting an average increase of 21 % for platelet activation. The results suggested that MDAPT could be served as a promising efficient inorganic hemostatic materials, which provided a feasible strategy to realize the high-valued utilization of natural mixed clay resources.


Assuntos
Argila , Compostos de Magnésio , Compostos de Silício , Compostos de Magnésio/química , Compostos de Magnésio/farmacologia , Argila/química , Animais , Compostos de Silício/química , Hemostáticos/farmacologia , Hemostáticos/química , Coagulação Sanguínea/efeitos dos fármacos , Coagulação Sanguínea/fisiologia , Hemostasia/efeitos dos fármacos , Hemostasia/fisiologia , Silicatos de Alumínio/química , Humanos
14.
J Med Eng Technol ; 48(1): 12-24, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38857023

RESUMO

Haemorrhage is the leading cause of battlefield deaths and second most common cause for civilian mortality worldwide. Biomaterials-based haemostatic agents are used to aid in bleeding stoppage; mesoporous bioactive glasses (MBGs) are candidates for haemostasis. Previously made Tantalum-containing MBG (Ta-MBG) powders' compositions were fabricated as electrospun fibres for haemostatic applications in the present study. The fibres were fabricated to address the challenges associated with the powder form: difficult to compress without gauze, getting washed away in profuse bleeding, generating dust in the surgical environment, and forming thick callus-difficult to remove for surgeons and painful for patients. Ta-MBGs were based on (80-x)SiO2-15CaO-5P2O5-xTa2O5 mol% compositions with x = 0 (0Ta), 0.5 (0.5Ta), 1 (1Ta), and 5 (5Ta) mol%. The present study details the fibres' in vitro analyses, elucidating their cytotoxic effects, and haemostatic capabilities and relating these observations to fibre chemistry and previously fabricated powders of the same glasses. As expected, when Ta addition is increased at the expense of silica, a new FTIR peak (non-bridging oxygen-silicon, Si-NBO) develops and Si-O-Si peaks become wider. Compared to 0Ta and 1Ta fibres, 0.5Ta show Si-O peaks with reduced intensity. The fibres had a weaker intensity of Si-NBO peaks and release fewer ions than powders. A reduced ion profile provides fibres with a stable matrix for clot formation. The ion release profile for 1Ta and 5Ta fibres was significantly lower than 0Ta and 0.5Ta fibres. Ta-MBGs were not found to be cytotoxic to primary rat fibroblasts using a methyl thiazolyl tetrazolium (MTT) assay. Furthermore, a modified activated partial thromboplastin time assay analysing the fibrin absorbance showed that the absorption increases from physiological clotting < 0Ta < 0.5Ta < 5Ta < commercial haemostat, Surgical SNoWTM, Ethicon, USA < 1Ta. Higher absorption signifies a stronger clot. It is concluded that Ta-MBG fibres can provide stable matrix for clot formation and 1Ta can potentially enhance clotting best among other Ta-MBGs.


Assuntos
Vidro , Tantálio , Tantálio/química , Vidro/química , Hemostáticos/química , Hemostáticos/farmacologia , Hemostasia/efeitos dos fármacos , Animais , Porosidade , Humanos , Ratos , Materiais Biocompatíveis/química
15.
Int J Biol Macromol ; 272(Pt 2): 132923, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38848835

RESUMO

Severe bleeding from deep and irregular wounds poses a significant challenge in prehospital and surgical settings. To address this issue, we developed a novel chitosan-based hemostatic dressing with a magnetic targeting mechanism using Fe3O4, termed bovine serum albumin-modified Fe3O4 embedded in porous α-ketoglutaric acid/chitosan (BSA/Fe3O4@KA/CS). This dressing enhances hemostasis by magnetically guiding the agent to the wound site. In vitro, the hemostatic efficacy of BSA/Fe3O4@KA/CS is comparable to that of commercial chitosan (Celox™) and is not diminished by the modification. In vivo, BSA/Fe3O4@KA/CS demonstrated superior hemostatic performance and reduced blood loss compared to Celox™. The hemostatic mechanism of BSA/Fe3O4@KA/CS includes the concentration of solid blood components through water absorption, adherence to blood cells, and activation of the endogenous coagulation pathway. Magnetic field targeting is crucial in directing the dressing to deep hemorrhagic sites. Additionally, safety assessments have confirmed the biocompatibility and biodegradability of BSA/Fe3O4@KA/CS. In conclusion, we introduce a novel approach to modify chitosan using magnetic guidance for effective hemostasis, positioning BSA/Fe3O4@KA/CS as a promising candidate for managing various wounds.


Assuntos
Bandagens , Quitosana , Hemostáticos , Soroalbumina Bovina , Quitosana/química , Soroalbumina Bovina/química , Animais , Hemostáticos/química , Hemostáticos/farmacologia , Porosidade , Ácidos Cetoglutáricos/química , Ácidos Cetoglutáricos/farmacologia , Bovinos , Masculino , Hemorragia/tratamento farmacológico , Hemorragia/terapia , Camundongos
16.
Int J Biol Macromol ; 273(Pt 1): 133032, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38862053

RESUMO

Collagen's unique properties promise hemostatic potential, but its sponge form's stability and mechanics need improvement. In this study, we developed a series of homeostatic sponges by co-assembling collagen and curdlan at different ratios into hydrogels, followed by freeze-drying treatment. The incorporation of curdlan into collagen sponges has been found to significantly enhance the sponge's properties, including increased porosity, elevated water uptake, improved elasticity, and enhanced resistance to degradation. In vitro cytotoxicity and hemolysis assays have demonstrated the biocompatibility and nontoxicity of composite sponges. In mouse liver perforation and incision models, the composite sponges achieved rapid coagulation within 67 s and 75 s, respectively, outperforming gauze and gelatin sponge in reducing blood loss. Furthermore, composite sponges demonstrated superior wound healing potential in mice full-thickness skin defects model, with accelerated healing rates observed at days 3, 7, and 14 compared to the control group. Overall, collagen/curdlan composite sponge show promise for hemostasis and wound healing applications.


Assuntos
Colágeno , Hemostasia , Cicatrização , beta-Glucanas , Animais , Cicatrização/efeitos dos fármacos , Colágeno/química , Colágeno/farmacologia , beta-Glucanas/farmacologia , beta-Glucanas/química , Camundongos , Hemostasia/efeitos dos fármacos , Pele/efeitos dos fármacos , Pele/lesões , Hidrogéis/química , Hidrogéis/farmacologia , Hemólise/efeitos dos fármacos , Hemostáticos/farmacologia , Hemostáticos/química , Porosidade , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Humanos , Masculino
17.
Int J Biol Macromol ; 273(Pt 1): 132989, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38852717

RESUMO

Developing a biodegradable sponge with rapid shape recovery and potent antibacterial and coagulation properties for traumatic hemostasis and anti-infection remains challenging. Herein, we fabricated quaternized silk fibroin (SF) sponges by freeze-drying under a constant cooling rate and modification with quaternary ammonium groups. We found the constant cooling rate enabled the sponges with a highly uniform pore structure, which provided excellent self-elasticity and shape recovery. Decoration with quaternary ammonium groups enhanced blood cells adhesion, aggregation, and activation, as well as resistance to infections from Staphylococcus aureus and Escherichia coli. The SF sponge had superior hemostatic capacity to gauze and commercial gelatin sponge in different hemorrhage models. The SF sponge exhibited favorable biodegradability and biocompatibility. Moreover, The SF sponge also promoted host cell infiltration, capillary formation, and tissue ingrowth, suggesting its potential for guiding tissue regeneration. The developed SF sponge holds great application prospects for traumatic hemostasis, anti-infection, and guiding tissue regeneration.


Assuntos
Materiais Biocompatíveis , Fibroínas , Hemostasia , Fibroínas/química , Fibroínas/farmacologia , Animais , Hemostasia/efeitos dos fármacos , Porosidade , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Staphylococcus aureus/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Hemostáticos/química , Hemostáticos/farmacologia , Ratos , Anti-Infecciosos/farmacologia , Anti-Infecciosos/química , Camundongos , Antibacterianos/farmacologia , Antibacterianos/química , Hemorragia/tratamento farmacológico
18.
ACS Appl Mater Interfaces ; 16(24): 30742-30754, 2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38841831

RESUMO

Uncontrolled hemorrhage and infection are the principal causes of mortality associated with trauma in both military and civilian medical settings. Modified starch granules have emerged as a safe hemostatic agent for irregular and noncompressible wounds, but their performance is constrained by limited hemostasis efficiency and modest antibacterial activity. This study reported a directed self-assembly approach for a multifunctional mesoporous starch-based microparticle loaded with chitosan and calcium ions (Ca@MSMP) used for rapid hemostasis and wound healing. Directed self-assembly of uniform Ca@MSMP with a hierarchical hollow structure in the presence of chitosan was confirmed by scanning electron microscopy (SEM) analysis and pore structure analysis. The resulting Ca@MSMP exhibited a well-defined spherical shape and uniform size of 1 µm and demonstrated excellent antibacterial activity (>95%) without hemolytic activity. Importantly, Ca@MSMP enhanced blood coagulation and platelet aggregation via the synergistic effect of rapid calcium release and chitosan-mediated electrostatic interactions, leading to a significant decrease in blood loss and reduction in hemostasis time in rat tail amputation and liver injury models. In comparative analyses, Ca@MSMP significantly outperformed the commercial hemostatic agent Quickclean, notably enhancing the healing of full-thickness skin wounds in vivo by effectively preventing infection. These results underscore the potential of this innovative hemostatic material in diverse clinical scenarios, offering effective solutions for the management of bleeding in wounds that are irregularly shaped and noncompressible.


Assuntos
Quitosana , Hemostasia , Hemostáticos , Amido , Cicatrização , Animais , Amido/química , Amido/farmacologia , Cicatrização/efeitos dos fármacos , Ratos , Hemostáticos/química , Hemostáticos/farmacologia , Hemostasia/efeitos dos fármacos , Quitosana/química , Quitosana/farmacologia , Porosidade , Ratos Sprague-Dawley , Cálcio/química , Antibacterianos/farmacologia , Antibacterianos/química , Coagulação Sanguínea/efeitos dos fármacos , Masculino , Hemorragia/tratamento farmacológico , Humanos , Staphylococcus aureus/efeitos dos fármacos
19.
ACS Appl Mater Interfaces ; 16(24): 30874-30889, 2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38856922

RESUMO

A new composite sponge assisted by magnetic field-mediated guidance was developed for effective hemostasis. It was based on polydopamine capillary-channel agarose (PDA-CAGA) sponge as matrix; meanwhile, the combination of deep eutectic solvent (DES, choline chloride:glycerol = 1:1, M/M)-dispersed Fe3O4 nanoparticles after fabrication by tannic acid (DES-Fe3O4@TA) was applied as hemostatic magnetic fluid. This sponge had oriented and aligned capillary channels realized by a 3D printed pattern, which endowed them with obvious shape memory and liquid absorption performance. Computational simulation was performed to describe the fluid status in channels; DES-Fe3O4@TA exhibited good magnetic properties, fluidity, and stability. In addition, the sponge driven to react rapidly with the bleeding site under the effect of a magnetic field presented a shorter hemostasis time (reduced by 85.02% in the tail and 81.07% in the liver of rats) and less blood loss (reduced by 97.08% in the tail and 91.50% in the liver) than those of medical gelatin sponge (GS). Meanwhile, the multifunctional material also exhibited better biocompatibility, procoagulant performance, and significant inhibition on S. aureus and E. coli than GS. As a whole, this work proposed a new strategy for rapid hemostasis by designing a magnetic field assisted composite bacteriostatic material, which also expanded the applications of green solvents in the clinical management field.


Assuntos
Escherichia coli , Sefarose , Staphylococcus aureus , Animais , Ratos , Sefarose/química , Staphylococcus aureus/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Solventes/química , Hemostasia/efeitos dos fármacos , Polímeros/química , Polímeros/farmacologia , Indóis/química , Antibacterianos/química , Antibacterianos/farmacologia , Hemostáticos/química , Hemostáticos/farmacologia , Campos Magnéticos , Masculino , Ratos Sprague-Dawley
20.
Molecules ; 29(9)2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38731410

RESUMO

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.


Assuntos
Anti-Inflamatórios , Cirsium , Hemostáticos , Extratos Vegetais , Animais , Coelhos , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/química , Anti-Inflamatórios/isolamento & purificação , Cirsium/química , Hemostáticos/farmacologia , Hemostáticos/química , Hemostáticos/isolamento & purificação , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Cromatografia Líquida de Alta Pressão , Inflamação/tratamento farmacológico , Inflamação/patologia , Masculino
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