RESUMEN

Uncontrolled non-compressible hemorrhage, which is often accompanied by coagulopathy, is a major cause of mortality following traumatic injuries in civilian and military populations. In this study, coagulopathy-independent injectable catechol-modified chitosan (CS-HCA) hemostatic materials featuring rapid shape recovery were fabricated by combining controlled sodium tripolyphosphate-crosslinking with hydrocaffeic acid (HCA) grafting. CS-HCA exhibited robust mechanical strength and rapid blood-triggered shape recovery. Furthermore, CS-HCA demonstrated superior blood-clotting ability, enhanced blood cell adhesion and activation, and greater protein adsorption than commercial hemostatic gauze and Celox. CS-HCA showed enhanced procoagulant and hemostatic capacities in a lethal liver-perforation wound model in rabbits, particularly in heparinized rabbits. CS-HCA is suitable for mass manufacturing and shows promise as a clinically translatable hemostat.

Asunto(s)

Catecoles , Quitosano , Hemorragia , Hemostáticos , Quitosano/química , Quitosano/farmacología , Animales , Conejos , Catecoles/química , Catecoles/farmacología , Hemorragia/tratamiento farmacológico , Hemostáticos/química , Hemostáticos/farmacología , Coagulación Sanguínea/efectos de los fármacos , Ácidos Cafeicos/química , Ácidos Cafeicos/farmacología , Masculino , Materiales Inteligentes/química , Inyecciones

RESUMEN

This review evaluates the evidence for the use of over-the-scope clips (OTSC), topical haemostatic agents (THA), and prophylactic embolisation (PE) in patients with peptic ulcer bleeding (PUB). The use of OTSC and THA may have the potential to increase the rate of endoscopic haemostasis in PUB not responding to conventional endoscopic treatment. In patients at high risk of recurrent bleeding, the performance of PE after achieving endoscopic haemostasis can reduce the risk of rebleeding and the need for surgery. Implementation of a local treatment protocol including these modalities may improve patient outcomes.

Asunto(s)

Embolización Terapéutica , Hemostasis Endoscópica , Úlcera Péptica Hemorrágica , Humanos , Úlcera Péptica Hemorrágica/terapia , Úlcera Péptica Hemorrágica/cirugía , Hemostasis Endoscópica/métodos , Embolización Terapéutica/métodos , Hemostáticos/uso terapéutico , Hemostáticos/administración & dosificación , Instrumentos Quirúrgicos

RESUMEN

Improper management of diabetic wound effusion and disruption of the endogenous electric field can lead to passive healing of damaged tissue, affecting the process of tissue cascade repair. This study developed an extracellular matrix sponge scaffold (K1P6@Mxene) by incorporating Mxene into an acellular dermal stroma-hydroxypropyl chitosan interpenetrating network structure. This scaffold is designed to couple with the endogenous electric field and promote precise tissue remodelling in diabetic wounds. The fibrous structure of the sponge closely resembles that of a natural extracellular matrix, providing a conducive microenvironment for cells to adhere grow, and exchange oxygen. Additionally, the inclusion of Mxene enhances antibacterial activity(98.89%) and electrical conductivity within the scaffold. Simultaneously, K1P6@Mxene exhibits excellent water absorption (39 times) and porosity (91%). It actively interacts with the endogenous electric field to guide cell migration and growth on the wound surface upon absorbing wound exudate. In in vivo experiments, the K1P6@Mxene sponge reduced the inflammatory response in diabetic wounds, increased collagen deposition and arrangement, promoted microvascular regeneration, Facilitate expedited re-epithelialization of wounds, minimize scar formation, and accelerate the healing process of diabetic wounds by 7 days. Therefore, this extracellular matrix sponge scaffold, combined with an endogenous electric field, presents an appealing approach for the comprehensive repair of diabetic wounds.

Asunto(s)

Antibacterianos , Cicatrización de Heridas , Cicatrización de Heridas/efectos de los fármacos , Animales , Antibacterianos/farmacología , Antibacterianos/química , Masculino , Matriz Extracelular/química , Hemostáticos/farmacología , Hemostáticos/química , Andamios del Tejido/química , Diabetes Mellitus Experimental/complicaciones , Ratones , Quitosano/química , Ratas , Humanos , Conductividad Eléctrica , Ratas Sprague-Dawley

RESUMEN

Uncontrolled hemorrhage stands as the primary cause of potentially preventable deaths following traumatic injuries in both civilian and military populations. Addressing this critical medical need requires the development of a hemostatic material with rapid hemostatic performance and biosafety. This work describes the engineering of a chitosan-based cryogel construct using thermo-assisted cross-linking with α-ketoglutaric acid after freeze-drying. The resulting cryogel exhibited a highly interconnected macro-porous structure with low thermal conductivity, exceptional mechanical properties, and great fluid absorption capacity. Notably, assessments using rabbit whole blood in vitro, as well as rat liver volume defect and femoral artery injury models simulating severe bleeding, showed the remarkable hemostatic performance of the chitosan cryogel. Among the cryogel variants with different chitosan molecular weights, the 150 kDa one demonstrated superior hemostatic efficacy, reducing blood loss and hemostasis time by approximately 73 % and 63 % in the hepatic model, and by around 60 % and 68 %, in the femoral artery model. Additionally, comprehensive in vitro and in vivo evaluations underscored the good biocompatibility of the chitosan cryogel. Taken together, these results strongly indicate that the designed chitosan cryogel configuration holds significant potential as a safe and rapid hemostatic material for managing severe hemorrhage.

Asunto(s)

Quitosano , Criogeles , Hemorragia , Hemostáticos , Quitosano/química , Quitosano/farmacología , Criogeles/química , Animales , Conejos , Hemorragia/terapia , Hemorragia/tratamiento farmacológico , Hemostáticos/química , Hemostáticos/farmacología , Ratas , Masculino , Ratas Sprague-Dawley , Arteria Femoral/lesiones , Porosidad , Hígado/efectos de los fármacos , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología , Reactivos de Enlaces Cruzados/química , Hemostasis/efectos de los fármacos

RESUMEN

Bleeding and bacterial infection are common problems associated with wound treatment, while effective blood clotting and vessel regeneration promotion are the primary considerations to design the wound dressing materials. This research presents a chitosan-based hydrogel with grafted quaternary ammonium and polyphosphate (QCSP hydrogel) as the antibacterial hemostatic dressing to achieve burn wound treatment. The tissue adhesion of the hydrogel sealed the blood flow and the polyphosphate grafted to the chitosan promoted the activation of coagulation factor V to enhance the hemostasis. At the same time, the grafted quaternary ammonium enhanced the antibacterial ability of the biodegradable hydrogel wound dressing. In addition, the polydopamine as a photothermal agent was composited into the hydrogel to enhance the antibacterial and reactive oxygen scavenging performance. The in vivo hemostasis experiment proved the polyphosphate enhanced the coagulation property. Moreover, this photothermal property of the composite hydrogel enhanced the burn wound repairing rate combined with the NIR stimulus. As a result, this hydrogel could have potential application in clinic as dressing material for hemostasis and infection prone would repairing.

Asunto(s)

Antibacterianos , Quemaduras , Quitosano , Hemostasis , Hidrogeles , Indoles , Polímeros , Cicatrización de Heridas , Quitosano/química , Quitosano/farmacología , Hidrogeles/química , Hidrogeles/farmacología , Quemaduras/tratamiento farmacológico , Quemaduras/terapia , Polímeros/química , Polímeros/farmacología , Antibacterianos/química , Antibacterianos/farmacología , Animales , Indoles/química , Indoles/farmacología , Cicatrización de Heridas/efectos de los fármacos , Hemostasis/efectos de los fármacos , Ratones , Hemostáticos/química , Hemostáticos/farmacología , Vendajes , Masculino , Ratas , Staphylococcus aureus/efectos de los fármacos , Escherichia coli/efectos de los fármacos , Ratas Sprague-Dawley , Pruebas de Sensibilidad Microbiana , Terapia Fototérmica/métodos

RESUMEN

The Ankaferd Blood Stopper (ABS) proves effective in managing various bleedings, particularly in surgical and dental procedures. This study assesses ABS efficacy endoscopically by less-experienced endoscopists for non-variceal upper gastrointestinal bleeding (NVUGB). Between 2016 and 2021, our hospital's Gastroenterology Department Endoscopy Unit conducted a retrospective data analysis of 653 patients who underwent endoscopy for NVUGB. The study included 202 patients who underwent endoscopic interventions performed by endoscopists with less than 3 years of experience. Based on the method used for endoscopic hemostasis, we classified those treated with ABS (either alone or as a second method) as group 1. In contrast, we classified patients treated with non-ABS hemostatic methods into Group 2. The study included 202 patients, with 96 (47.52%) in Group 1 and 106 (52.48%) in Group 2. All patients in Group 1 achieved bleeding control, while 4 patients in Group 2 initially did not achieve bleeding control; however, bleeding control was subsequently established following ABS administration. After 1 month of follow-up, mortality occurred in 3 out of 202 patients (1.48%), and all these cases were in Group 2. There is a significant difference in the need for blood transfusion between the groups (P < .001). Regarding the bleeding source, bulbus ulcer and gastric cancer were more prevalent in Group 2. On the other hand, although statistical significance was not reached in the comparison of rebleeding rates between groups, numerically, a higher incidence of recurrent bleeding was observed in Group 2 (Group 1: 3 [3.1%], Group 2: 8 [7.5%]; P = .167). Additionally, a similar relationship was noted among intensive care admissions (Group 1: 5 [5.2%]; Group 2: 7 [6.6%]; P = .675). In the group that used ABS, there were significantly higher rates of hypotension, tachycardia, syncope, and the need for transfusion than in the other group. In medical practice, this distinction often stems from the shared preference of clinicians to use ABS as a salvage method in cases of more severe bleeding. Considering all the findings, it is evident that using ABS through endoscopy in cases of NVUGIB significantly improves procedural success, irrespective of the endoscopist's experience level.

Asunto(s)

Hemorragia Gastrointestinal , Extractos Vegetales , Humanos , Masculino , Hemorragia Gastrointestinal/tratamiento farmacológico , Femenino , Estudios Retrospectivos , Persona de Mediana Edad , Anciano , Extractos Vegetales/uso terapéutico , Hemostasis Endoscópica/métodos , Hemostáticos/uso terapéutico , Gastroenterólogos , Competencia Clínica , Adulto , Resultado del Tratamiento

RESUMEN

Various seeds, including sea buckthorn (Hippophae rhamnoides L.) seeds, are sources of different bioactive compounds. They can show anti-inflammatory, hypoglycemic, anti-hyperlipidemic, antibacterial, antioxidant, or other biological properties in in vitro and in vivo models. Our preliminary in vitro results have demonstrated that the extracts from raw (no thermal processing) and roasted (thermally processed) sea buckthorn seeds have antioxidant potential and anticoagulant activity. However, it was unclear which compounds were responsible for these properties. Therefore, in continuation of our previous study, the extracts were fractionated by C18 chromatography. Phytochemical analysis of three fractions (a, b, and c) from raw sea buckthorn seeds and four fractions (d, e, f, and g) from roasted sea buckthorn seeds were performed. Several in vitro assays were also conducted to determine the antioxidant and procoagulant/anticoagulant potential of the fractions and two of their major constituents-isorhamnetin 3-O-ß-glucoside7-O-α-rhamnoside and serotonin. LC-MS analyses showed that serotonin is the dominant constituent of fractions c and f, which was tentatively identified on the basis of its HRMS and UV spectra. Moreover, fractions c and f, as well as b and e, contained different B-type proanthocyanidins. Fractions b and e consisted mainly of numerous glycosides of kaempferol, quercetin, and isorhamnetin. The results of oxidative stress assays (measurements of protein carbonylation, lipid peroxidation, and thiol groups oxidation) showed that out of all the tested fractions, fraction g (isolated from roasted seeds and containing mainly dihexoses, and serotonin) demonstrated the strongest antioxidant properties.

Asunto(s)

Antioxidantes , Hippophae , Extractos Vegetales , Semillas , Antioxidantes/farmacología , Antioxidantes/química , Semillas/química , Hippophae/química , Extractos Vegetales/farmacología , Extractos Vegetales/química , Fitoquímicos/farmacología , Fitoquímicos/química , Serotonina/metabolismo , Hemostáticos/farmacología , Hemostáticos/aislamiento & purificación , Humanos , Anticoagulantes/farmacología , Anticoagulantes/química , Animales

RESUMEN

Reducing unnecessary blood loss in hemostasis is a major challenge for traditional hemostatic materials due to uncontrolled blood absorption. Tuning the hydrophilic and hydrophobic properties of hemostatic materials provides a road to reduce blood loss. Here, we developed a superhydrophobic aerogel that enabled remarkably reduced blood loss. The aerogel was fabricated with polydopamine-coated and fluoroalkyl chain-modified bacterial cellulose via a directional freeze-drying method. Primarily, the hydrophobic feature prevented blood from uncontrolled absorption by the material and overflowing laterally. Additionally, the aerogel had a dense network of channels that allowed it to absorb water from blood due to the capillary effect, and fluoroalkyl chains trapped the blood cells entering the channels to form a compact barrier via hydrophobic interaction at the bottom of the aerogel, causing quick fibrin generation and blood coagulation. The animal experiments reveal that the aerogel reduced the hemostatic time by 68% and blood loss by 87 wt % compared with QuikClot combat gauze. The study demonstrates the superiority of superhydrophobic aerogels for hemostasis and provides new insights into the development of hemostatic materials.

Asunto(s)

Celulosa , Hemostasis , Hemostáticos , Interacciones Hidrofóbicas e Hidrofílicas , Nanofibras , Celulosa/química , Celulosa/farmacología , Animales , Nanofibras/química , Hemostáticos/química , Hemostáticos/farmacología , Hemostasis/efectos de los fármacos , Geles/química , Polímeros/química , Polímeros/farmacología , Ratones , Humanos , Coagulación Sanguínea/efectos de los fármacos , Indoles/química

RESUMEN

Biopolymer aerogel is a new type of material with potential applications in the biomedical field. Silk fibroin is of particular interest as a raw material with good biocompatibility and degradable. However, the low mechanical strength and small specific surface area of silk fibroin aerogels limit its further development. Herein, a fast water absorption, highly specific surface area and mechanically strong of aerogels were prepared using low crystal silk fibroin nanofibers (SNF), sol-gel process, solvent exchange and supercritical carbon dioxide (CO2) drying method. The resulting Aero-Sc displayed highly specific surface area (251 m2/g), porosity (97.6 %) and water absorption capacity (1200 %). Furthermore, with rapid water absorption and stronger erythrocyte adhesion, the Aero-Sc showed highly effective hemostasis in vitro. In vivo, animal experiments on rat liver hemorrhage model confirmed that SNF aerogels have a less blood loss (312 ± 29 mg) and faster hemostatic time (92 ± 13 s) than commercially gelatin sponge (p < 0.05). The unique properties of silk fibroin nanofibers aerogel developed in this study has great potential to be a safe and effective hemostatic medical device.

Asunto(s)

Fibroínas , Geles , Hemostasis , Nanofibras , Nanofibras/química , Animales , Ratas , Fibroínas/química , Fibroínas/farmacología , Hemostasis/efectos de los fármacos , Geles/química , Porosidad , Hemorragia/tratamiento farmacológico , Fenómenos Mecánicos , Hemostáticos/química , Hemostáticos/farmacología , Propiedades de Superficie , Agua/química , Masculino , Bombyx/química , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología

RESUMEN

BACKGROUND: Warfarin patients who need dental extraction face the problem of bleeding and no sufficient hemostasis results in dry socket and postoperative pain. This study aimed to evaluate and compare the efficacy of the topical application of tranexamic acid-soaked absorbable Gelfoam (TXA-Gel) and saline-soaked absorbable Gelfoam (saline-Gel) in relieving postoperative pain following bilateral simple extraction of permanent mandibular molars in warfarin patients. METHODS: This was a randomized, triple-blinded, split-mouth, active-controlled clinical trial. It was performed at the Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Damascus University, between November 2021 and October 2023. 60 bilateral permanent mandibular molars, which were indicated for simple extraction in 30 warfarin patients randomly assigned into two groups according to the topical hemostatic agents after extraction used: Group 1: control group, saline-Gel (n = 30). Group 2: TXA-Gel (n = 30). A simple randomization method was performed by flipping a coin. The primary outcome measure was the visual analogue scale (VAS). The intensity of pain was evaluated at the baseline (t0), and on the 1st (t1), 2nd (t2), 3rd (t3), 4th (t4), 5th (t5), 6th (t6), and 7th (t7) days following extraction. The Kolmogorov-Smirnov test and the Mann-Whitney U test were performed. The level of significance was set at 0.05 (p < 0.05). RESULTS: The mean vas scores was 4.17 ± 1.76 at t1 and decreased to 0.73 ± 0.78 at t7 in the TXA-Gel group. However, in the Gelfoam group, the mean vas scores was 4.83 ± 2.18 at t1 and decreased to 1.80 ± 1.00 at t7. The results of the Mann-Whitney U test showed that there was no statistically significant difference between the two groups at t1 (p = 0.236) and t2 (p = 0.155). However, there was a statistically significance difference at the rest time points (p < 0.05). CONCLUSIONS: TXA-Gel played a prominent role in alleviating post-extraction pain in warfarin patients. TRIAL REGISTRATION: The trail was retrospectively registered at the ISRCTN registry (ISRCTN71901901).

Asunto(s)

Administración Tópica , Esponja de Gelatina Absorbible , Dolor Postoperatorio , Extracción Dental , Ácido Tranexámico , Warfarina , Humanos , Ácido Tranexámico/administración & dosificación , Ácido Tranexámico/uso terapéutico , Warfarina/uso terapéutico , Warfarina/administración & dosificación , Masculino , Dolor Postoperatorio/prevención & control , Dolor Postoperatorio/tratamiento farmacológico , Femenino , Esponja de Gelatina Absorbible/uso terapéutico , Adulto , Dimensión del Dolor , Persona de Mediana Edad , Hemostáticos/uso terapéutico , Hemostáticos/administración & dosificación , Anticoagulantes/uso terapéutico , Anticoagulantes/administración & dosificación , Antifibrinolíticos/administración & dosificación , Antifibrinolíticos/uso terapéutico , Diente Molar/cirugía

RESUMEN

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.

Asunto(s)

Criopreservación , Hemostáticos , Hidrogeles , Nanoestructuras , Sefarosa , Animales , Hidrogeles/química , Hemostáticos/farmacología , Hemostáticos/química , Ratas , Sefarosa/química , Criopreservación/métodos , Nanoestructuras/química , Fibrina/química , Masculino , Hepatectomía/métodos , Humanos , Hemostasis/efectos de los fármacos , Ratas Sprague-Dawley

RESUMEN

Severe bleeding and bacterial infections pose significant challenges to the global public health. Effective hemostatic materials have the potential to be used for rapid control of bleeding at the wound site. In this study, mesoporous silica nanoparticles (MSN) were doped with zinc ions (MSN@Zn) and subsequently functionalized with carboxyl (-COOH) groups through post-grafting, resulting in (MSN@Zn-COOH). The results demonstrated the successful functionalization of carboxyl groups on the surface of MSN@Zn mesoporous materials with minimal impact on the morphology. The released zinc ions showed potent antibacterial activity (above ∼80 %) against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). In vitro and in vivo assessments of MSN@Zn-COOH revealed excellent hemostatic effects and favorable blood compatibility. Hemolysis percentages associated with MSN@Zn-COOH exhibited noteworthy reductions in comparison to MSN. Furthermore, a decrease in APTT (a test evaluating the intrinsic coagulation pathway) of modified MSN@Zn indicated enhanced hemostasis, supported by their negative zeta potential (∼ -14 to -43 mV). Importantly, all samples showed no cytotoxicity. This work underscores the potential of MSN@Zn-COOH, with its combined hemostatic performance and antibacterial activity, for emergency clinical applications.

Asunto(s)

Antibacterianos , Escherichia coli , Hemostáticos , Nanopartículas , Dióxido de Silicio , Staphylococcus aureus , Propiedades de Superficie , Zinc , Antibacterianos/farmacología , Antibacterianos/química , Dióxido de Silicio/química , Dióxido de Silicio/farmacología , Escherichia coli/efectos de los fármacos , Staphylococcus aureus/efectos de los fármacos , Nanopartículas/química , Zinc/química , Zinc/farmacología , Hemostáticos/farmacología , Hemostáticos/química , Porosidad , Animales , Pruebas de Sensibilidad Microbiana , Humanos , Hemólisis/efectos de los fármacos , Hemostasis/efectos de los fármacos , Tamaño de la Partícula , Ratones

RESUMEN

Developing an effective and user-friendly hemostatic agent is highly desired in the treatment of hemorrhage. Inspired by the natural nanostructure and abundant hydroxyl groups of cellulose and clay minerals, we designed an aerogel (HNTs/TOCNs) composed of halloysite nanotubes (HNTs) and TEMPO-oxidized cellulose nanofibers (TOCNs) with a hierarchical porous structure for the treatment of bleeding, using a simple and environmentally friendly self-assembly method. TOCNs formed a three-dimensional porous scaffold with excellent water-holding capacity. The incorporation of HNTs enhanced the hemostatic efficiency and mechanical properties of the 3D framework. The large interlayer spaces and wide channels within the HNTs/TOCNs aerogel provided rapid passage for blood, facilitating blood concentration and offering ample room for interactions between the HNTs/TOCNs aerogel and platelets, erythrocytes, and coagulation factors, thereby promoting hemostasis. Benefiting from the natural hemostatic properties and well-designed structure, the HNTs/TOCNs aerogel displayed excellent hemostatic performance both in vitro and in vivo. Notably, the hemostatic time of HNTs/TOCNs-2 was only 74 ± 8 s, which is approximately 50 % shorter than the blank control (151 ± 20 s) in liver femoral artery injury model. This design of an HNTs/TOCNs aerogel presents a unique opportunity to enhance hemostatic efficacy by synergizing the advantages of natural materials.

Asunto(s)

Celulosa , Arcilla , Hemostasis , Nanofibras , Nanofibras/química , Porosidad , Animales , Hemostasis/efectos de los fármacos , Arcilla/química , Celulosa/química , Geles/química , Hemostáticos/química , Hemostáticos/farmacología , Ratas , Hemorragia/tratamiento farmacológico , Masculino , Nanotubos/química , Óxidos N-Cíclicos/química , Ratones

RESUMEN

This study presents a thrombin-loaded cationized chitosan (TCCS) sponge with highly effective hemostatic and antibacterial activity. The TCCS sponge, prepared using a multistep method, features a porous structure, favorable mechanical properties, excellent water absorption ability, and shape recovery triggered by water or blood. The TCCS sponge exhibited strong antibacterial activity against Methicillin-resistant Staphylococcus aureus and Escherichia coli. Additionally, it demonstrated enhanced procoagulant and hemostatic efficacy in rat tail amputation and rat liver perforation wound models compared to commercial hemostats. Furthermore, the sponge exhibited favorable biocompatibility and biosafety. These findings suggest that the TCCS sponge has substantial potential for practical applications in managing severe hemorrhages and bacterial infections.

Asunto(s)

Antibacterianos , Quitosano , Hemostasis , Hemostáticos , Staphylococcus aureus Resistente a Meticilina , Trombina , Quitosano/química , Quitosano/farmacología , Animales , Antibacterianos/farmacología , Antibacterianos/química , Ratas , Hemostáticos/química , Hemostáticos/farmacología , Trombina/farmacología , Hemostasis/efectos de los fármacos , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Cationes/química , Escherichia coli/efectos de los fármacos , Masculino , Porosidad

RESUMEN

Carboxymethyl chitosan (CMCS) and sodium alginate (SA), which are excellent polysaccharide-based hemostatic agents, are capable of forming polyelectrolyte complexes (PEC) through electrostatic interactions. However, CMCS/SA PEC sponges prepared by the conventional sol-gel process exhibited slow liquid absorption rate and poor mechanical properties post-swelling. In this work, a novel strategy involving freeze casting followed by acetic acid vapor treatment to induce electrostatic interactions was developed to fabricate novel PEC sponges with varying CMCS/SA mass ratios. Compared to sol-gel process sponge, the novel sponge exhibited a higher density of electrostatic interactions, resulting in denser pore walls that resist re-gelation and swelling according to FTIR, XRD, and SEM analyses. Additionally, the liquid absorption kinetics, as well as compression and tension tests, demonstrated that the novel sponge had significantly improved rapid blood absorption capacity and mechanical properties. Furthermore, in vitro coagulation and drug release studies showed that the novel sponge had a lower blood clotting index and clotting time, along with a slower drug release rate after loading with berberine hydrochloride, showcasing its potential as a rapid hemostatic dressing with controlled drug release capabilities.

Asunto(s)

Alginatos , Vendajes , Quitosano , Liberación de Fármacos , Hemostasis , Quitosano/química , Quitosano/análogos & derivados , Alginatos/química , Hemostasis/efectos de los fármacos , Porosidad , Animales , Sistemas de Liberación de Medicamentos , Hemostáticos/química , Hemostáticos/farmacología , Coagulación Sanguínea/efectos de los fármacos

RESUMEN

Background: Desmopressin (1-deamino-8-D-arginine vasopressin [DDAVP]) has demonstrated efficacy as a treatment option for patients with inherited bleeding disorders. Because of individuals' variable response to the medication, it is recommended to complete a challenge to document appropriate hemostatic response to the medication before recommending its use prior to surgical procedures or treatment of bleeding symptoms. The project aimed to reduce the errors in hemostatic response assessments for patients with bleeding disorders undergoing a DDAVP challenge (process outcome), particularly timing and number of blood samples drawn, from an error rate baseline of 36% to 0% by December 2021 and sustained for one year. Method: Plan-Do-Study-Act methodology was employed for this qualitative improvement initiative. Interventions designed and implemented included: an order set with medication doses and corresponding laboratory orders as clinically indicated for the bleeding disorder indication, clinical procedure guidelines for infusion nurses to follow, hemostasis nurse coordination of appointments with patients, and family education. Results: Baseline data on 22 patients who completed a DDAVP challenge demonstrated a 36% error rate not involving doses of medication administered. Errors encountered included improper timing of laboratory draw after DDAVP administration, incomplete laboratory evaluation, laboratory results displayed incorrectly due to testing orders released at once instead of in a sequential manner. These interventions resulted in a reduction of DDAVP challenge errors to 0% that were sustained for one year. Conclusion: Improvement in procedural medication administration and appropriate laboratory evaluation of patients undergoing a DDAVP challenge leads to a complete and reliable assessment of hemostatic response following medication administration.

Asunto(s)

Desamino Arginina Vasopresina , Hemostáticos , Mejoramiento de la Calidad , Humanos , Desamino Arginina Vasopresina/uso terapéutico , Desamino Arginina Vasopresina/administración & dosificación , Adolescente , Adulto Joven , Masculino , Femenino , Niño , Hemostáticos/uso terapéutico , Hemostáticos/administración & dosificación , Adulto , Trastornos de la Coagulación Sanguínea/tratamiento farmacológico , Preescolar

RESUMEN

The healing of diabetic wounds has long been a significant challenge in the field of medicine. The elevated sugar levels surrounding diabetic wounds create a conducive environment for harmful bacterial growth, resulting in purulent infections that impede the healing process. Thus, the development of a biomaterial that can enhance the healing of diabetic wounds holds great importance. This study developed electrospun dressings for wound healing by combining traditional Chinese medicine and clay. The study utilized electrospinning technology to prepare polyvinyl alcohol (PVA) nanofiber membranes containing ASB and HNTs. These ASB@HNTs-PVA nanofiber membranes demonstrated rapid hemostasis, along with antibacterial and anti-inflammatory properties, facilitating the recovery of type 2 diabetic (T2D) wounds. Various analyses were conducted to assess the performance of the composite nanofiber membrane, including investigations into its biocompatibility and hemostatic abilities through antibacterial experiments, cell experiments, and mouse liver tail bleeding experiments. Western blot analysis confirmed that the composite nanofiber membrane could decrease the levels of inflammatory factors IL-1ß and TNF-α. A type 2 diabetic mouse model was utilized, with wounds artificially induced on the backs of mice. Application of the nanofiber membrane to the wounds further confirmed its anti-inflammatory effects and ability to enhance wound healing in vivo.

Asunto(s)

Antiinflamatorios , Diabetes Mellitus Tipo 2 , Hemostáticos , Nanofibras , Alcohol Polivinílico , Cicatrización de Heridas , Animales , Nanofibras/química , Cicatrización de Heridas/efectos de los fármacos , Alcohol Polivinílico/química , Ratones , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Hemostáticos/farmacología , Hemostáticos/química , Masculino , Humanos , Piel/patología , Piel/efectos de los fármacos , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Diabetes Mellitus Experimental , Vendajes , Células RAW 264.7

RESUMEN

INTRODUCTION: Reduced thrombin generation is an important component of post cardiopulmonary bypass (CPB) coagulopathy. To replenish coagulation factors and enhance thrombin generation in bleeding surgical patients, frozen plasma (FP) and four-factor prothrombin complex concentrate (4F-PCC) are used. However, the efficacy-safety balance of 4F-PCC relative to FP in cardiac surgery is unconfirmed. METHODS AND ANALYSIS: LEX-211 (FARES-II) is an active-control, randomised, phase 3 study comparing two coagulation factor replacement therapies in bleeding adult cardiac surgical patients at 12 hospitals in Canada and the USA. The primary objective is to determine whether 4F-PCC (Octaplex/Balfaxar, Octapharma) is clinically non-inferior to FP for haemostatic effectiveness. Inclusion criteria are any index (elective or non-elective) cardiac surgery employing CPB and coagulation factor replacement with 4F-PCC or FP ordered in the operating room for bleeding management. Patients will be randomised to receive 1500 or 2000 international units of 4F-PCC or 3 or 4 units of FP, depending on body weight. The primary endpoint of haemostatic treatment response is 'effective' if no additional haemostatic intervention is required from 60 min to 24 hours after the first initiation of 4F-PCC or FP; or 'ineffective' if any other haemostatic intervention (including a second dose of study drug) is required. An estimated 410 evaluable patients will be required to demonstrate non-inferiority (one-sided α of 0.025, power ≥90%, non-inferiority margin 0.10). Secondary outcomes include transfusions, bleeding-related clinical endpoints, coagulation parameters and safety. ETHICS AND DISSEMINATION: The trial has been approved by the institutional review boards of all participating centres. Trial completion is anticipated at the end of 2024, and results will be disseminated via publications in peer-reviewed journals and conference presentations in 2025. The results will advance our understanding of coagulation management in bleeding surgical patients, potentially reducing the need for allogeneic blood products and improving outcomes in surgical patients. TRIAL REGISTRATION NUMBER: NCT05523297.

Asunto(s)

Factores de Coagulación Sanguínea , Procedimientos Quirúrgicos Cardíacos , Plasma , Humanos , Factores de Coagulación Sanguínea/uso terapéutico , Procedimientos Quirúrgicos Cardíacos/efectos adversos , Hemorragia Posoperatoria/etiología , Canadá , Adulto , Ensayos Clínicos Fase III como Asunto , Puente Cardiopulmonar/efectos adversos , Hemostáticos/uso terapéutico , Estados Unidos

RESUMEN

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.

Asunto(s)

Calcio , Hemorragia , Polimerizacion , Polifosfatos , Animales , Polifosfatos/química , Polifosfatos/farmacología , Calcio/química , Ratas , Hemorragia/prevención & control , Hemorragia/tratamiento farmacológico , Hemostáticos/química , Hemostáticos/farmacología , Coagulación Sanguínea/efectos de los fármacos , Ratas Sprague-Dawley , Masculino , Hemostasis/efectos de los fármacos , Iones/química

RESUMEN

Our laboratory recently developed a new class of high surface area, honeycomb Nanoclay Microsphere Framework absorbents (NMFs) that prompt rapid hemostasis. In the present work, we propose a novel approach to develop antibacterial Topical Hemostatic Agents (THAs) by anchoring silver nanoparticles (AgNPs) onto NMFs. This combination was obtained by a chemical co-reduction approach, followed by freeze-processing, and was shown to ensure stability and on-site delivery of AgNPs, without altering the hemostatic properties of NMFs. Silver-loaded NMFs showed no change in their unique architecture and led to a 55% increase in clot strength, compared to standard control plasma or commercially available THA, and a significant decrease in mean fibrin fiber diameter. Silver nanoparticles were successfully released when solubilized and prevented the growth of both Pseudomonas aeruginosa and Staphylococcus aureus at concentrations of 22 and 30 ppm of silver released, respectively. Overall, cell mortality was between 9.1 ± 5.1% and 6.3 ± 3.2%, depending on AgNP concentration, confirming a low cytotoxicity. Silver-loaded nanoclay microsphere frameworks appear to constitute promising candidates as topical hemostatic agents for secondary management of hemostasis when infection control is needed.

Asunto(s)

Antibacterianos , Arcilla , Hemostáticos , Nanopartículas del Metal , Pseudomonas aeruginosa , Plata , Staphylococcus aureus , Antibacterianos/farmacología , Antibacterianos/química , Plata/química , Plata/farmacología , Hemostáticos/farmacología , Hemostáticos/química , Staphylococcus aureus/efectos de los fármacos , Staphylococcus aureus/crecimiento & desarrollo , Pseudomonas aeruginosa/efectos de los fármacos , Nanopartículas del Metal/química , Arcilla/química , Humanos , Hemostasis/efectos de los fármacos