RÉSUMÉ
Tumor cells can survive when detached from the extracellular matrix (ECM) or lose cell-cell connections, a phenomenon known as anoikis-resistance (AR). AR is closely associated with tumor cell metastasis and recurrence, enabling tumor cells to disseminate, migrate, and invade after detachment. To address this issue, a novel intervention method combining intraoperative hemostasis with multifunctional nanozyme driven-enhanced chemodynamic therapy (ECDT) has been proposed, which holds the potential to weaken the AR capability of tumor cells and suppress tumor recurrence. Here, a nanocomposite containing a dendritic mesoporous nanoframework with Cu2+ was developed using an anion-assisted approach after surface PEG grafting and glucose oxidase (GOx) anchoring (DMSN-Cu@GOx/PEG). DMSN-Cu@GOx/PEG was further encapsulated in a thermal-sensitive hydrogel (H@DMSN-Cu@GOx/PEG). DMSN-Cu@GOx/PEG utilizes its high peroxidase (POD) activity to elevate intracellular ROS levels, thereby weakening the AR capability of bladder cancer cells. Additionally, through its excellent catalase (CAT) activity, DMSN-Cu@GOx/PEG converts the high level of hydrogen peroxide (H2O2) catalyzed by intracellular GOx into oxygen (O2), effectively alleviating tumor hypoxia, downregulating hypoxia-inducible factor-1α (HIF-1α) expression, inhibiting epithelial-mesenchymal transition (EMT) processes, and ultimately suppressing the migration and invasion of bladder cancer cells. Interestingly, in vivo results showed that the thermosensitive hydrogel H@DMSN-Cu@GOx/PEG could rapidly gel at body temperature, forming a gel film on wounds to eliminate residual tumor tissue after tumor resection surgery. Importantly, H@DMSN-Cu@GOx/PEG exhibited excellent hemostatic capabilities, effectively enhancing tissue coagulation during post-tumor resection surgery and mitigating the risk of cancer cell dissemination and recurrence due to surgical bleeding. Such hydrogels undoubtedly possess strong surgical application. Our developed novel nanosystem and hydrogel can inhibit the AR capability of tumor cells and prevent recurrence post-surgery. This study represents the first report of using dendritic mesoporous silica-based nanoreactors for inhibiting the AR capability of bladder cancer cells and suppressing tumor recurrence post-surgery, providing a new avenue for developing strategies to impede tumor recurrence after surgery.
Sujet(s)
Glucose oxidase , Hydrogels , Hydrogels/composition chimique , Hydrogels/pharmacologie , Animaux , Humains , Lignée cellulaire tumorale , Souris , Glucose oxidase/pharmacologie , Glucose oxidase/métabolisme , Glucose oxidase/composition chimique , Récidive tumorale locale , Souris nude , Souris de lignée BALB C , Nanocomposites/composition chimique , Nanocomposites/usage thérapeutique , Polyéthylène glycols/composition chimique , Polyéthylène glycols/pharmacologie , Espèces réactives de l'oxygène/métabolisme , Cuivre/composition chimique , Cuivre/pharmacologie , Hémostase/effets des médicaments et des substances chimiques , Mouvement cellulaire/effets des médicaments et des substances chimiques , Peroxyde d'hydrogène/pharmacologieRÉSUMÉ
Chitin and its deacetylated form, chitosan, have demonstrated remarkable versatility in the realm of biomaterials. Their exceptional biocompatibility, antibacterial properties, pro- and anticoagulant characteristics, robust antioxidant capacity, and anti-inflammatory potential make them highly sought-after in various applications. This review delves into the mechanisms underlying chitin/chitosan's biological activity and provides a comprehensive overview of their derivatives in fields such as tissue engineering, hemostasis, wound healing, drug delivery, and hemoperfusion. However, despite the wealth of studies on chitin/chitosan, there exists a notable trend of homogeneity in research, which could hinder the comprehensive development of these biomaterials. This review, taking a clinician's perspective, identifies current research gaps and medical challenges yet to be addressed, aiming to pave the way for a more sustainable future in chitin/chitosan research and application.
Sujet(s)
Matériaux biocompatibles , Chitine , Chitosane , Ingénierie tissulaire , Chitosane/composition chimique , Chitosane/pharmacologie , Chitine/composition chimique , Humains , Matériaux biocompatibles/composition chimique , Matériaux biocompatibles/pharmacologie , Animaux , Ingénierie tissulaire/méthodes , Cicatrisation de plaie/effets des médicaments et des substances chimiques , Systèmes de délivrance de médicaments , Antibactériens/composition chimique , Antibactériens/pharmacologie , Hémostase/effets des médicaments et des substances chimiquesRÉSUMÉ
Introduction: Elevated ambient pollution exposure is potentially linked to thromboembolism. However, the mechanisms by which particulate matter (PM) interferes with the balance of hemostatic system remain unclear. This study investigates PM-mediated hemostatic changes in individuals across unique seasonal variations of ambient pollution. Methods: This prospective study was conducted between February and July 2020 during alterations in ambient pollution in Chiang Mai, Thailand. Blood tests from 30 healthy subjects were assessed at four-week intervals, four times in total. Various coagulation tests, including prothrombin time (PT), activated partial thromboplastin time (aPTT), von Willebrand factor (vWF), platelet count, and platelet functions, were evaluated. A mixed-effects model was used to analyze the impact of high PM2.5 and PM10 on hemostatic parameters. Results: Thirty male subjects with mean age of 38.9 ± 8.2 years, were included. High levels of PM2.5 and PM10 were significantly associated with PT shortening, with no such effect observed in aPTT. PM2.5 and PM10 values also positively correlated with vWF function, while vWF antigen levels remained unchanged. Soluble P-selectin showed a strong positive association with PM2.5 and PM10 levels. Platelet function analysis revealed no correlation with PM values. Conclusion: Short-term exposure to elevated PM2.5 and PM10 concentrations was linked to shortened PT and enhanced vWF function in healthy individuals. Exploring the impact of these changes on clinically relevant thrombosis is crucial. Additional studies on the pathogenesis of pollution-related thrombosis are warranted for maintaining good health.
Sujet(s)
Pollution de l'air , Plaquettes , Hémostase , Matière particulaire , Humains , Matière particulaire/effets indésirables , Mâle , Adulte , Hémostase/effets des médicaments et des substances chimiques , Thaïlande , Études prospectives , Pollution de l'air/effets indésirables , Plaquettes/effets des médicaments et des substances chimiques , Polluants atmosphériques/effets indésirables , Adulte d'âge moyen , Facteur de von Willebrand/métabolisme , Facteur de von Willebrand/analyse , Numération des plaquettes , Exposition environnementale/effets indésirables , Saisons , Tests de coagulation sanguineRÉSUMÉ
The development of efficient hemostatic materials is crucial for achieving rapid hemorrhage control and effective wound healing. Inorganic polyphosphate (polyP) is recognized as an effective modulator of the blood coagulation process. However, the specific effect of polyP chain length on coagulation is not yet fully understood. Furthermore, calcium ions (Ca2+) are essential for the coagulation process, promoting multiple enzyme-catalyzed reactions within the coagulation cascade. Hence, calcium ion-coupled polyphosphate powders with three different degrees of polymerization (CaPP-n, n = 20, 50, and 1500) are synthesized by an ion-exchange reaction. CaPP exhibits a crystalline phase at a low polymerization degree and transitions to an amorphous phase as the polymerization degree increases. Notably, the addition of Ca2+ enhances the wettability of polyP, and CaPP promotes hemostasis, with varying degrees of effectiveness related to chain length. CaPP-50 exhibits the most promising hemostatic performance, with the lowest blood clotting index (BCI, 12.1 ± 0.7%) and the shortest clotting time (302.0 ± 10.5 s). By combining Ca2+ with polyP of medium-chain length, CaPP-50 demonstrates an enhanced ability to accelerate the adhesion and activation of blood cells, initiate the intrinsic coagulation cascade, and form a stable blood clot, outperforming both CaPP-20 and CaPP-1500. The hemostatic efficacy of CaPP-50 is further validated using rat liver bleeding and femoral artery puncture models. CaPP-50 is proven to possess hemostatic properties comparable to those of commercial calcium-based zeolite hemostatic powder and superior to kaolin. In addition, CaPP-50 exhibits excellent biocompatibility and long-term storage stability. These results suggest that CaPP-50 has significant clinical and commercial potential as an active inorganic hemostatic agent for rapid control of bleeding.
Sujet(s)
Calcium , Hémorragie , Polymérisation , Polyphosphates , Animaux , Polyphosphates/composition chimique , Polyphosphates/pharmacologie , Calcium/composition chimique , Rats , Hémorragie/prévention et contrôle , Hémorragie/traitement médicamenteux , Hémostatiques/composition chimique , Hémostatiques/pharmacologie , Coagulation sanguine/effets des médicaments et des substances chimiques , Rat Sprague-Dawley , Mâle , Hémostase/effets des médicaments et des substances chimiques , Ions/composition chimiqueRÉSUMÉ
Uncontrolled bleeding during surgery is associated with high mortality and prolonged hospital stay, necessitating the use of hemostatic agents. Fibrin sealant patches offer an efficient solution to achieve hemostasis and improve patient outcomes in liver resection surgery. We have previously demonstrated the efficacy of a nanostructured fibrin-agarose hydrogel (NFAH). However, for the widespread distribution and commercialization of the product, it is necessary to develop an optimal preservation method that allows for prolonged stability and facilitates storage and distribution. We investigated cryopreservation as a potential method for preserving NFAH using trehalose. Structural changes in cryopreserved NFAH (Cryo-NFAH) were investigated and comparative in vitro and in vivo efficacy and safety studies were performed with freshly prepared NFAH. We also examined the long-term safety of Cryo-NFAH versus TachoSil in a rat partial hepatectomy model, including time to hemostasis, intra-abdominal adhesion, hepatic hematoma, inflammatory factors, histopathological variables, temperature and body weight, hemocompatibility and cytotoxicity. Structural analyses demonstrated that Cryo-NFAH retained most of its macro- and microscopic properties after cryopreservation. Likewise, hemostatic efficacy assays showed no significant differences with fresh NFAH. Safety evaluations indicated that Cryo-NFAH had a similar overall profile to TachoSil up to 40 days post-surgery in rats. In addition, Cryo-NFAH demonstrated superior hemostatic efficacy compared with TachoSil while also demonstrating lower levels of erythrolysis and cytotoxicity than both TachoSil and other commercially available hemostatic agents. These results indicate that Cryo-NFAH is highly effective hemostatic patch with a favorable safety and tolerability profile, supporting its potential for clinical use.
Sujet(s)
Cryoconservation , Hémostatiques , Hydrogels , Nanostructures , Agarose , Animaux , Hydrogels/composition chimique , Hémostatiques/pharmacologie , Hémostatiques/composition chimique , Rats , Agarose/composition chimique , Cryoconservation/méthodes , Nanostructures/composition chimique , Fibrine/composition chimique , Mâle , Hépatectomie/méthodes , Humains , Hémostase/effets des médicaments et des substances chimiques , Rat Sprague-DawleyRÉSUMÉ
The study focuses on developing a bioactive shape memory sponge to address the urgent demand for short-term rapid hemostasis and long-term wound healing in noncompressible hemorrhage cases. A composite sponge was created by spontaneously generating pores and double cross-linking under mild conditions using biomimetic collagen fibril (BCF) and oxidized alginate (OA) as natural backbone, combined with an inert calcium source (Ca) from CaCO3-GDL slow gelation mechanism. The optimized BCF/OACa (5/5) sponge efficiently absorbed blood after compression and recovered to its original state within 11.2 ± 1.3 s, achieving physical hemostatic mechanism. The composite sponge accelerated physiological coagulation by promoting platelet adhesion and activation through BCF, as well as enhancing endogenous and exogenous hemostatic pathways by Ca2+. Compared to commercial PVA expanding hemostatic sponge, the composite sponge reduced bleeding volume and shortened hemostasis time in rat liver injury pick and perforation wound models. Additionally, it stimulated fibroblast migration and differentiation, thus promoting wound healing. It is biodegradable with low inflammatory response and promotes granulation tissue regeneration. In conclusion, this biocomposite sponge provides multiple hemostatic pathways and biochemical support for wound healing, is biologically safe and easy to fabricate, process and use, with significant potential for clinical translation and application.
Sujet(s)
Alginates , Matériaux biomimétiques , Collagène , Hémorragie , Hémostatiques , Cicatrisation de plaie , Alginates/composition chimique , Alginates/pharmacologie , Animaux , Cicatrisation de plaie/effets des médicaments et des substances chimiques , Collagène/composition chimique , Rats , Hémorragie/traitement médicamenteux , Matériaux biomimétiques/composition chimique , Matériaux biomimétiques/pharmacologie , Hémostatiques/pharmacologie , Hémostatiques/composition chimique , Mâle , Rat Sprague-Dawley , Hémostase/effets des médicaments et des substances chimiques , Oxydoréduction , Adhésivité plaquettaire/effets des médicaments et des substances chimiquesSujet(s)
Bévacizumab , Hémorragie gastro-intestinale , Humains , Hémorragie gastro-intestinale/induit chimiquement , Hémorragie gastro-intestinale/étiologie , Bévacizumab/effets indésirables , Bévacizumab/usage thérapeutique , Mâle , Inhibiteurs de l'angiogenèse/effets indésirables , Inhibiteurs de l'angiogenèse/usage thérapeutique , Sujet âgé , Hémostase/effets des médicaments et des substances chimiques , Lymphomes/traitement médicamenteux , Lymphomes/complications , Femelle , Adulte d'âge moyenRÉSUMÉ
Transformation of a fibrous mat into a three-dimensional (3D) scaffold opens up abundant innovative prospects in biomedical research, particularly for studying both soft as well as hard tissues. Electrospun nanofibers, which mimic the extracellular matrix have attracted significant attention in various studies. This research focuses on rapidly converting a fibrous mat made of polycaprolactone (PCL)/pluronic F-127 (PF-127) with different percentages of monetite calcium phosphate (MCP) into desirable 3D matrix cotton using a unique gas foaming technology. These matrix cottons possess biomimetic properties and have oriented porous structures. Using this innovative technique, various shapes of 3D matrix cotton, such as squares, hollow tubes, and other customizable forms, were successfully produced. Importantly, these 3D matrix cottons showed a consistent distribution of monetite particles with total porosity ranging from 90% to 98%. The structure of the 3D matrix cotton, its water/blood absorption capacity, the potential for causing non-hemolysis, and rapid hemostatic properties were thoroughly investigated. Additionally, periodontal cells were cultured on the 3D matrix cotton to assess their viability and morphology, revealing promising results. Furthermore, a coculture study involving NIH-3T3 and MG-63 cells on the 3D matrix cotton showed spheroidal formation within 24 h. Notably, in vitro assessments indicated that the matrix cotton containing 15% monetite (PCL-MMC15%) exhibited superior absorbent capabilities, excellent cell viability, and rapid hemostatic characteristics. Subsequently, the effectiveness of PCL-MMC15% in promoting mandibular bone regeneration was evaluated through an in vivo study on rabbits using a mandibular injury model. The results demonstrated that PCL-MMC15% facilitated the resolution of defects in the mandibular region by initiating new bone formation. Therefore, the presented 3D matrix cotton (PCL-MMC15%) shows significant promise for applications in both mandibular bone regeneration and hemostasis.
Sujet(s)
Matériaux biocompatibles , Régénération osseuse , Fibre de coton , Mandibule , Polyesters , Structures d'échafaudage tissulaires , Animaux , Souris , Régénération osseuse/effets des médicaments et des substances chimiques , Matériaux biocompatibles/composition chimique , Structures d'échafaudage tissulaires/composition chimique , Polyesters/composition chimique , Humains , Cellules NIH 3T3 , Phosphates de calcium/composition chimique , Lapins , Porosité , Hémostase/effets des médicaments et des substances chimiques , Hémostatiques/pharmacologie , Hémostatiques/usage thérapeutique , Hémostatiques/composition chimique , Nanofibres/composition chimiqueRÉSUMÉ
The development of an effective hemostatic agents is of vital importance for saving wounded individuals from uncontrolled hemorrhage, which is the main reason for preventable death after accidental injury. However, current high-performance hemostatic agents suffer from a cumbersome preparation procedures and poor biocompatibility. Here, we engineered a cellulosic-derived aerogel material by simply controlling the drying process of cellulose regeneration for fast hemostasis. Four different freeze-drying pretreatments were investigated. As compared with the other three, the cellulosic aerogel material prepared without freezing pretreatment exhibited the lowest crystallinity (21.3%) and the highest body fluid absorption capacity (20.3 times that of its own weight) due to its super hierarchical porous structure, which led to an excellent hemostatic performance in vitro blood coagulation (≈100 s). Moreover, the addition of gelatin and diatomite in the material could tune the functional groups and electrostatic properties of the aerogel and further enhance its hemostatic performance. Various characterizations, including X-ray diffraction (XRD), fourier transform infrared spectroscopy (FTIR), X-ray nanocomputed tomography (CT), scanning electron microscopy (SEM), and zeta potential analysis, were carried out to probe the structure-function relationship of the prepared material, and its mechanism of fast hemostasis was thereafter revealed. The results indicate that the developed aerogel is a cost-effective and feasibly scalable hemostatic material suitable for practical use in industry.
Sujet(s)
Cellulose , Hémostase , Hémostatiques , Cellulose/composition chimique , Hémostatiques/composition chimique , Hémostatiques/pharmacologie , Hémostase/effets des médicaments et des substances chimiques , Porosité , Animaux , Coagulation sanguine/effets des médicaments et des substances chimiques , Lyophilisation , Spectroscopie infrarouge à transformée de Fourier , Diffraction des rayons X , Humains , Matériaux biocompatibles/composition chimique , Matériaux biocompatibles/pharmacologie , Gélatine/composition chimiqueRÉSUMÉ
BACKGROUND: Critical shortages in the national blood supply have led to a re-evaluation of previously overlooked donor sources for blood products. As a part of that effort, red blood cells collected from therapeutic phlebotomy of donors on testosterone replacement therapy (TRT) have been conditionally approved for transfusion. However, platelets from TRT donors are not currently approved for use due to limited data on effects of supraphysiologic testosterone on recipient safety and platelet function. The objective of this study was to provide a comprehensive profile of phenotype and function in platelets from TRT and control donors. STUDY DESIGN AND METHODS: Platelets in plasma were collected from TRT and control donors (N = 10 per group; age- and sex-matched) and stored at room temperature for 7 days. On storage Day 1 (D1) and Day 7 (D7), platelet products were analyzed for platelet count, metabolic parameters (i.e., glucose, lactate, mitochondrial function), surface receptor expression, aggregation, thrombin generation, and thrombus formation under physiological flow conditions. RESULTS: TRT donor platelets were not significantly different than control donor platelets in terms of count, surface phenotype, metabolic function, ability to aggregate, thrombin generation, or ability to form occlusive thrombus under arterial flow regimes. Both groups were similar to each other by D7, but had significantly lost hemostatic function compared to D1. DISCUSSION: Platelets derived from donors undergoing TRT have similar phenotypic and functional profiles compared to those derived from control donors. This suggests that therapeutic phlebotomy of TRT donors may provide a useful source for platelet products.
Sujet(s)
Donneurs de sang , Plaquettes , Conservation de sang , Hormonothérapie substitutive , Testostérone , Humains , Testostérone/sang , Testostérone/pharmacologie , Plaquettes/effets des médicaments et des substances chimiques , Plaquettes/métabolisme , Mâle , Phénotype , Adulte d'âge moyen , Adulte , Hémostase/effets des médicaments et des substances chimiques , FemelleRÉSUMÉ
Nasal tamponade is a commonly employed and highly effective treatment method for preventing nasal bleeding. However, the current nasal packing hemostatic materials exhibit some limitations, such as low hemostatic efficiency, the potential for causing secondary injury when removed from the nasal cavity, limited intelligence in their design, and an inability to promote the healing of nasal mucosa wounds. Herein, we report the fabrication of a smart cellulose aerogel through the covalent cross-linking of carboxymethyl cellulose (CMC) macromolecules, while incorporating one-dimensional cellulose nanofibers (CNF) and two-dimensional MXene as reinforcing network scaffolds and conductive fillers. The abundant hydrogen and ether bonds in aerogels make them possess high elasticity in both dry and wet states, which can be compressed 100 times at 90 % deformation with a stress loss of <10 % under water. The highly elastic aerogels can be filled into the narrow nasal passages, pressuring the capillaries and reducing the amount of bleeding. Moreover, the strong interface between aerogels and blood can promote red blood cell aggregation, platelet adhesion and activation, activate intrinsic coagulation pathway and accelerate blood coagulation, resulting in excellent hemostatic ability. Furthermore, the aerogels exhibit excellent hemocompatibility and cytocompatibility, making them suitable for wound healing and capable of fully healing wounds within 15 days. Notably, the presence of MXene causes the aerogels to form a conductive network when exposed to blood, enabling them to perform real-time hemostatic monitoring without removing the dressing. This innovative biomedical aerogel, prepared from natural materials, shows excellent potential for applications in rapid nasal hemostasis.
Sujet(s)
Matériaux biocompatibles , Cellulose , Épistaxis , Hémostatiques , Cicatrisation de plaie , Cicatrisation de plaie/effets des médicaments et des substances chimiques , Matériaux biocompatibles/composition chimique , Matériaux biocompatibles/pharmacologie , Animaux , Cellulose/composition chimique , Cellulose/pharmacologie , Hémostatiques/pharmacologie , Hémostatiques/composition chimique , Épistaxis/traitement médicamenteux , Gels/composition chimique , Élasticité , Humains , Nanofibres/composition chimique , Coagulation sanguine/effets des médicaments et des substances chimiques , Hémostase/effets des médicaments et des substances chimiques , LapinsRÉSUMÉ
A novel gingival retraction cord named P/TA@CSy was prepared using chitosan yarns (CSy) loaded with tranexamic acid (TA) and Propolis (P). P/TA@CSy has good toughness with a breaking strength of 41.3 Pa, benefiting from the twisting structure and Propolis coating. A short coagulation time of 456 s was achieved for P/TA@CSy because of the potent blood absorption ability from the effective attachment of tranexamic acid. Moreover, excellent antibacterial ability was obtained with the antibacterial rates against E. coli of 94.73 %, S. aureus of 99.99 % and S. mutans of 99.99 %, contributing to Propolis's antibacterial ability. In addition, suppression of the expression of pro-inflammatory cytokines (IL-6 and TNF-α) was found, which could prevent wound infection. P/TA@CSy displayed excellent cytocompatibility with the cell activity of 100 % after 24 h. Therefore, P/TA@CSy could rapidly respond to gingival hemostasis and infection prevention, showing excellent potential in dental treatment.
Sujet(s)
Antibactériens , Chitosane , Hémostase , Propolis , Acide tranéxamique , Chitosane/composition chimique , Chitosane/pharmacologie , Antibactériens/pharmacologie , Antibactériens/composition chimique , Acide tranéxamique/pharmacologie , Acide tranéxamique/composition chimique , Propolis/composition chimique , Propolis/pharmacologie , Hémostase/effets des médicaments et des substances chimiques , Gencive/effets des médicaments et des substances chimiques , Gencive/cytologie , Humains , Animaux , Escherichia coli/effets des médicaments et des substances chimiques , Staphylococcus aureus/effets des médicaments et des substances chimiques , Souris , Tests de sensibilité microbienneRÉSUMÉ
The key to saving lives is to achieve instant and effective sealing hemostasis in the event of emergency bleeding. Herein, a plant oil-based EMTA/Zn2+ bioadhesive is prepared by a facile reaction of epoxidized soybean oil (ESO) with methacrylic acid (MAA) and tannic acid (TA), followed by the addition of zinc ions for coordination with TA. The EMTA/Zn2+ bioadhesive can be rapidly cured in situ at the wound site through photo-cross-linking under ultraviolet (UV) light-emitting diode (LED) irradiation within 30 s, achieving ultrastrong wet-tissue adhesion performance of 92.4 and 51.8 kPa to porcine skin and aortic skin after 7 days underwater, respectively. Especially, the EMTA/Zn2+ bioadhesive exhibits outstanding sealing performance in vitro with the high burst pressure of 525 mmHg (70 kPa) and 337.5 mmHg (45 kPa) to porcine skin and aortic skin, respectively. Moreover, the EMTA/Zn2+ bioadhesive not only has outstanding hemocompatibility and good biodegradability but also exhibits excellent cytocompatibility and antibacterial properties. Notably, the EMTA/Zn2+ bioadhesive has remarkable instant sealing hemostatic ability for hemorrhaging liver in vivo. Therefore, the prepared plant oil-based EMTA/Zn2+ bioadhesive can serve as a charming alternative candidate for instant sealing hemostasis in clinical applications, especially in traumatic internal organs and arterial bleeding.
Sujet(s)
Hémostase , Animaux , Suidae , Hémostase/effets des médicaments et des substances chimiques , Huiles végétales/composition chimique , Huiles végétales/pharmacologie , Hémostatiques/composition chimique , Hémostatiques/pharmacologie , Adhésifs tissulaires/composition chimique , Adhésifs tissulaires/pharmacologie , Zinc/composition chimique , Zinc/pharmacologie , Souris , Humains , Hémorragie/traitement médicamenteux , Peau/effets des médicaments et des substances chimiques , Matériaux biocompatibles/composition chimique , Matériaux biocompatibles/pharmacologie , Tanins/composition chimique , Tanins/pharmacologie , Méthacrylates/composition chimique , Méthacrylates/pharmacologieRÉSUMÉ
The Helicobacter pylori infection in the stomach is the key reason for gastric mucosal bleeding. Eliminating gastric Helicobacter pylori by oral treatment remains difficult due to the presence of the gastric mucosal layer, which acts as a physical barrier to drugs via oral administration. In this study, a magnetic-navigable microneedle drug delivery platform (MNsD) for oral administration, featuring differential dual-mode drug release rate, was designed to fulfil rapid gastric hemostasis and overcome the gastric barriers for long-lasting Helicobacter pylori inhibition in stomach. MNs-D was created by rationally loading the carrier substrate, which was composed of silk fibroin with variable solubility, with antibiotics and hemostats. In vitro experiments showed MNs-D may sustainably eradicate Helicobacter pylori in stimulated gastric juices with long-lasting drug release (79 % in 24 h) and quickly establish hemostasis with instant drug release (92 % within 60 s). Most importantly, in vivo studies demonstrated MNs-D overcame the unsettling gastric mucosal barrier in traditional therapies of oral administration by insertion into the GML under magnetic navigation, resulting in sustained antibiotic release for long-lasting Helicobacter pylori eradiation (99 %). For differential dual-mode medication release against gastric Helicobacter pylori infections, this study may have firstly examined the effects of magnetic navigated microneedles administered orally.
Sujet(s)
Antibactériens , Systèmes de délivrance de médicaments , Fibroïne , Muqueuse gastrique , Infections à Helicobacter , Helicobacter pylori , Aiguilles , Helicobacter pylori/effets des médicaments et des substances chimiques , Animaux , Fibroïne/composition chimique , Infections à Helicobacter/traitement médicamenteux , Infections à Helicobacter/microbiologie , Administration par voie orale , Antibactériens/pharmacologie , Antibactériens/administration et posologie , Antibactériens/pharmacocinétique , Antibactériens/composition chimique , Muqueuse gastrique/métabolisme , Muqueuse gastrique/microbiologie , Muqueuse gastrique/effets des médicaments et des substances chimiques , Libération de médicament , Hémostase/effets des médicaments et des substances chimiques , Estomac/microbiologie , Estomac/effets des médicaments et des substances chimiques , Mâle , SourisRÉSUMÉ
Cotton gauze is commonly used in initial emergency care. However, its high hydrophilicity and limited clotting capacity can lead to the excessive absorption of blood, resulting in unnecessary blood loss. Herein, an amphiphilic Janus cotton gauze with excellent moisture management and enhanced blood coagulation has been developed via in situ generating bioactive glass (BG) onto the cotton gauze (CG), and then attaching cardanol (CA) onto one side of the BG-loaded CG (CG@BG) via click reaction. The Janus gauze (CA-CG@BG) has asymmetric wetting properties with a hydrophilic side (CA-CG@BGHL) and a hydrophobic side (HBCA-CG@BG). When applied to hemostatic, the porous and active BG on CA-CG@BGHL can rapidly initiate coagulation cascade to form a robust thrombus. CA on HBCA-CG@BG can entangled with each other, creating a hydrophobic barrier that prevents blood from flowing out. The hemostatic performance of CA-CG@BG is superior to that of CG in both rats and pigs. Interestingly, CA-CG@BG possesses unidirectional exudate removal. When applied to wound healing, the exudate can penetrate the hydrophobic HBCA-CG@BG to the hydrophilic CA-CG@BGHL, resulting in faster wound healing than CG. CA-CG@BG exhibits excellent cytocompatibility and hemocompatibility. This unique Janus dressing shows promise as a potential material for clinical applications in the future.
Sujet(s)
Bandages , Coagulation sanguine , Hémostase , Interactions hydrophobes et hydrophiles , Cicatrisation de plaie , Animaux , Cicatrisation de plaie/effets des médicaments et des substances chimiques , Coagulation sanguine/effets des médicaments et des substances chimiques , Hémostase/effets des médicaments et des substances chimiques , Rats , Fibre de coton , Hémostatiques/composition chimique , Hémostatiques/pharmacologie , SuidaeRÉSUMÉ
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.
Sujet(s)
ADN , Pièges extracellulaires , Hémostase , Hémostatiques , Hydrogels , Cicatrisation de plaie , Animaux , Pièges extracellulaires/métabolisme , Pièges extracellulaires/effets des médicaments et des substances chimiques , ADN/composition chimique , Mâle , Hydrogels/composition chimique , Hydrogels/pharmacologie , Rats , Hémostase/effets des médicaments et des substances chimiques , Cicatrisation de plaie/effets des médicaments et des substances chimiques , Hémostatiques/pharmacologie , Hémostatiques/composition chimique , Rat Sprague-Dawley , Hémorragie , Humains , Granulocytes neutrophiles/métabolisme , Modèles animaux de maladie humaineRÉSUMÉ
For patients with hemophilia A and high-titer inhibitors treated with bypassing agents there are no reliable methods to assess treatment effect. We investigated the utility of global hemostatic methods in assessing treatment with bypassing agents (rFVIIa or activated prothrombin complex [aPCC]). All patients with hemophilia A and inhibitors followed at the Coagulation Unit or the Pediatric Coagulation Unit at Karolinska University Hospital aged 6 years and above were eligible for this noninterventional study. Baseline plasma samples were spiked with bypassing agents in increasing concentrations (aPCC 50 U/kg, 100 U/kg, 150 U/kg, and rFVIIa 90 µg/kg and 270 µg/kg) in vitro. For patients treated with factor concentrates or bypassing agents follow-up samples were collected (in vivo tests). The samples were analyzed using overall hemostatic potential (OHP), and calibrated automated thrombogram, Calibrated Automated Thrombogram (CAT). Nine patients with hemophilia A with inhibitors were included. Spiking with rFVIIa normalized the coagulation potential in 6/8 samples, in 3 only with high dose. Only one sample did not improve adequately after spiking with aPCC. The improvement in hemostasis was reliably shown by both CAT and OHP. The baseline potential was, however, more often measurable by OHP compared to CAT. Factor concentrate had been administered to 5 patients normalizing the hemostatic potential in vivo in 2 (without spiking). The hemostatic improvement induced by spiking with rFVIIa or aPCC is shown by OHP and CAT, but the results have to be evaluated in larger cohorts.
Sujet(s)
Facteur VIIa , Hémophilie A , Humains , Hémophilie A/traitement médicamenteux , Hémophilie A/sang , Projets pilotes , Enfant , Mâle , Facteur VIIa/pharmacologie , Facteur VIIa/usage thérapeutique , Adolescent , Protéines recombinantes/usage thérapeutique , Protéines recombinantes/pharmacologie , Hémostase/effets des médicaments et des substances chimiques , Facteurs de la coagulation sanguine/pharmacologie , Facteurs de la coagulation sanguine/usage thérapeutique , Hémostatiques/usage thérapeutique , Hémostatiques/pharmacologie , Adulte , FemelleRÉSUMÉ
Developing a hemostatic material suitable for rapid hemostasis remains a challenge. This study presents a novel aminated gelatin sponge cross-linked with dialdehyde starch, exhibiting excellent biocompatibility and hemostatic ability. This aminated gelatin sponge features hydrophilic surface and rich porous structure with a porosity of up to 80 %. The results show that the aminated gelatin sponges exhibit superior liquid absorption capacity and can absorb up to 30-50 times their own mass of simulated body fluid within 5 min. Compared with the commercial gelatin hemostatic sponge and non-aminated gelatin hemostatic sponge, the aminated gelatin hemostatic sponge can accelerate the hemostatic process through electrostatic interactions, demonstrating superior hemostatic performance in both in vitro and in vivo hemostasis tests. The aminated gelatin sponge can effectively control the hemostatic time within 80 s in the in vivo rat femoral artery injury model, significantly outperforming both commercial and non-aminated gelatin sponges. In addition, the aminated gelatin sponge also exhibits good biocompatibility and certain antibacterial properties. The proposed aminated gelatin sponge has very good application prospects for the management of massive hemorrhage.
Sujet(s)
Matériaux biocompatibles , Gélatine , Hémostatiques , Amidon , Animaux , Amidon/composition chimique , Amidon/pharmacologie , Amidon/analogues et dérivés , Rats , Matériaux biocompatibles/composition chimique , Matériaux biocompatibles/pharmacologie , Hémostatiques/composition chimique , Hémostatiques/pharmacologie , Gélatine/composition chimique , Gélatine/pharmacologie , Mâle , Porosité , Rat Sprague-Dawley , Hémorragie/traitement médicamenteux , Hémostase/effets des médicaments et des substances chimiques , Éponge de gélatine résorbable/composition chimique , Éponge de gélatine résorbable/pharmacologie , Réactifs réticulants/composition chimique , Artère fémorale/effets des médicaments et des substances chimiques , HumainsRÉSUMÉ
Hydrogels, as an emerging biomaterial, have found extensive use in the healing of wounds due to their distinctive physicochemical structure and functional properties. Moreover, hydrogels can be made to match a range of therapeutic requirements for materials used in wound healing through specific functional modifications. This review provides a step-by-step explanation of the processes involved in cutaneous wound healing, including hemostasis, inflammation, proliferation, and reconstitution, along with an investigation of the factors that impact these processes. Furthermore, a thorough analysis is conducted on the various stages of the wound healing process at which functional hydrogels are implemented, including hemostasis, anti-infection measures, encouraging regeneration, scar reduction, and wound monitoring. Next, the latest progress of multifunctional hydrogels for wound healing and the methods to achieve these functions are discussed in depth and categorized for elucidation. Finally, perspectives and challenges associated with the clinical applications of multifunctional hydrogels are discussed.
Sujet(s)
Hydrogels , Peau , Cicatrisation de plaie , Cicatrisation de plaie/effets des médicaments et des substances chimiques , Hydrogels/composition chimique , Hydrogels/pharmacologie , Humains , Animaux , Peau/effets des médicaments et des substances chimiques , Peau/traumatismes , Matériaux biocompatibles/composition chimique , Matériaux biocompatibles/pharmacologie , Hémostase/effets des médicaments et des substances chimiquesRÉSUMÉ
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.