RESUMO
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.
Assuntos
Quitosana , Criogéis , Hemorragia , Hemostáticos , Quitosana/química , Quitosana/farmacologia , Criogéis/química , Animais , Coelhos , Hemorragia/terapia , Hemorragia/tratamento farmacológico , Hemostáticos/química , Hemostáticos/farmacologia , Ratos , Masculino , Ratos Sprague-Dawley , Artéria Femoral/lesões , Porosidade , Fígado/efeitos dos fármacos , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Reagentes de Ligações Cruzadas/química , Hemostasia/efeitos dos fármacosRESUMO
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.
Assuntos
Antibacterianos , Queimaduras , Quitosana , Hemostasia , Hidrogéis , Indóis , Polímeros , Cicatrização , Quitosana/química , Quitosana/farmacologia , Hidrogéis/química , Hidrogéis/farmacologia , Queimaduras/tratamento farmacológico , Queimaduras/terapia , Polímeros/química , Polímeros/farmacologia , Antibacterianos/química , Antibacterianos/farmacologia , Animais , Indóis/química , Indóis/farmacologia , Cicatrização/efeitos dos fármacos , Hemostasia/efeitos dos fármacos , Camundongos , Hemostáticos/química , Hemostáticos/farmacologia , Bandagens , Masculino , Ratos , Staphylococcus aureus/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Ratos Sprague-Dawley , Testes de Sensibilidade Microbiana , Terapia Fototérmica/métodosRESUMO
Achieving timely and effective hemorrhage control is imperative for the survival of individuals with severe bleeding. Hemostatic materials, by enhancing the natural cell-based coagulation response, are essential tools in modern and military medical practice for controlling bleeding, especially in emergency and surgical settings. Here, we report a new type of composite hemostatic material with two different aluminosilicate-based components, kaolin and zeolite, which synergistically work together in different stages of the coagulation cascade reactions. Kaolin can effectively activate the clotting factor FXII in the early stage, and zeolite can accumulate and assemble FXa and FVa on its surface and thereafter lead to the formation of highly active thrombin in the later stage. The synergistic action mechanism between kaolin and zeolite significantly boosts the levels of FXIIa and FXa, and it also greatly enhances plateau thrombin activity. For practical application, a kaolin-modified zeolite gauze is fabricated, and it demonstrates excellent hemostatic effectiveness. Compared to the combat gauze currently used in front-line treatment, it reduces blood loss by 75% and shortens hemostasis time by 33% in a rabbit femoral artery injury model. In addition, this kaolin-zeolite gauze has no heat release problem and a nearly zero particle shedding rate, which greatly decreases the safety risk compared to current commercial inorganic-based hemostatic gauzes.
Assuntos
Hemorragia , Hemostáticos , Caulim , Zeolitas , Caulim/química , Caulim/farmacologia , Zeolitas/química , Zeolitas/farmacologia , Animais , Coelhos , Hemorragia/tratamento farmacológico , Hemostáticos/química , Hemostáticos/farmacologia , Coagulação Sanguínea/efeitos dos fármacos , Trombina/química , HumanosRESUMO
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.
Assuntos
Celulose , Hemostasia , Hemostáticos , Interações Hidrofóbicas e Hidrofílicas , Nanofibras , Celulose/química , Celulose/farmacologia , Animais , Nanofibras/química , Hemostáticos/química , Hemostáticos/farmacologia , Hemostasia/efeitos dos fármacos , Géis/química , Polímeros/química , Polímeros/farmacologia , Camundongos , Humanos , Coagulação Sanguínea/efeitos dos fármacos , Indóis/químicaRESUMO
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.
Assuntos
Catecóis , Quitosana , Hemorragia , Hemostáticos , Quitosana/química , Quitosana/farmacologia , Animais , Coelhos , Catecóis/química , Catecóis/farmacologia , Hemorragia/tratamento farmacológico , Hemostáticos/química , Hemostáticos/farmacologia , Coagulação Sanguínea/efeitos dos fármacos , Ácidos Cafeicos/química , Ácidos Cafeicos/farmacologia , Masculino , Materiais Inteligentes/química , InjeçõesRESUMO
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.
Assuntos
Antibacterianos , Cicatrização , Cicatrização/efeitos dos fármacos , Animais , Antibacterianos/farmacologia , Antibacterianos/química , Masculino , Matriz Extracelular/química , Hemostáticos/farmacologia , Hemostáticos/química , Alicerces Teciduais/química , Diabetes Mellitus Experimental/complicações , Camundongos , Quitosana/química , Ratos , Humanos , Condutividade Elétrica , Ratos Sprague-DawleyRESUMO
Development of a low-cost and biocompatible hydrogel dressing with antimicrobial, antioxidant, and low swelling properties is important for accelerating wound healing. Here, a multifunctional alginate hydrogel dressing was fabricated using the D-(+)-gluconic acidδ-lactone/CaCO3system. The addition of hyaluronic acid and tannic acid (TA) provides the alginate hydrogel with anti-reactive oxygen species (ROS), hemostatic, and pro-wound healing properties. Notably, soaking the alginate hydrogel in a poly-ϵ-lysine (EPL) aqueous solution enables the alginate hydrogel to be di-crosslinked with EPL through electrostatic interactions, forming a dense network resembling 'armor' on the surface. This simple one-step soaking strategy provides the alginate hydrogel with antibacterial and anti-swelling properties. Swelling tests demonstrated that the cross-sectional area of the fully swollen multifunctional alginate hydrogel was only 1.3 times its initial size, thus preventing excessive wound expansion caused by excessive swelling. After 5 h ofin vitrorelease, only 7% of TA was cumulatively released, indicating a distinctly slow-release behavior. Furthermore, as evidenced by the removal of 2,2-diphenyl-1-picrylhydrazyl free radicals, this integrated alginate hydrogel systems demonstrate a notable capacity to eliminate ROS. Full-thickness skin wound repair experiment and histological analysis of the healing site in mice demonstrate that the developed multifunctional alginate hydrogels have a prominent effect on extracellular matrix formation and promotion of wound closure. Overall, this study introduces a cost-effective and convenient multifunctional hydrogel dressing with high potential for clinical application in treating open wounds.
Assuntos
Alginatos , Antibacterianos , Sequestradores de Radicais Livres , Hemostáticos , Hidrogéis , Espécies Reativas de Oxigênio , Taninos , Cicatrização , Cicatrização/efeitos dos fármacos , Alginatos/química , Animais , Hidrogéis/química , Hidrogéis/farmacologia , Camundongos , Antibacterianos/farmacologia , Antibacterianos/química , Sequestradores de Radicais Livres/química , Sequestradores de Radicais Livres/farmacologia , Hemostáticos/química , Hemostáticos/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Taninos/química , Taninos/farmacologia , Ácido Hialurônico/química , Ácido Hialurônico/farmacologia , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Antioxidantes/farmacologia , Antioxidantes/química , Bandagens , Masculino , Picratos/química , Compostos de Bifenilo/química , Polilisina/químicaRESUMO
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.
Assuntos
Criopreservação , Hemostáticos , Hidrogéis , Nanoestruturas , Sefarose , Animais , Hidrogéis/química , Hemostáticos/farmacologia , Hemostáticos/química , Ratos , Sefarose/química , Criopreservação/métodos , Nanoestruturas/química , Fibrina/química , Masculino , Hepatectomia/métodos , Humanos , Hemostasia/efeitos dos fármacos , Ratos Sprague-DawleyRESUMO
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.
Assuntos
Anti-Inflamatórios , Diabetes Mellitus Tipo 2 , Hemostáticos , Nanofibras , Álcool de Polivinil , Cicatrização , Animais , Nanofibras/química , Cicatrização/efeitos dos fármacos , Álcool de Polivinil/química , Camundongos , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hemostáticos/farmacologia , Hemostáticos/química , Masculino , Humanos , Pele/patologia , Pele/efeitos dos fármacos , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Diabetes Mellitus Experimental , Bandagens , Células RAW 264.7RESUMO
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 â¼80â¯%) 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 (â¼ -14 to -43â¯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.
Assuntos
Antibacterianos , Escherichia coli , Hemostáticos , Nanopartículas , Dióxido de Silício , Staphylococcus aureus , Propriedades de Superfície , Zinco , Antibacterianos/farmacologia , Antibacterianos/química , Dióxido de Silício/química , Dióxido de Silício/farmacologia , Escherichia coli/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos , Nanopartículas/química , Zinco/química , Zinco/farmacologia , Hemostáticos/farmacologia , Hemostáticos/química , Porosidade , Animais , Testes de Sensibilidade Microbiana , Humanos , Hemólise/efeitos dos fármacos , Hemostasia/efeitos dos fármacos , Tamanho da Partícula , CamundongosRESUMO
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.
Assuntos
Celulose , Argila , Hemostasia , Nanofibras , Nanofibras/química , Porosidade , Animais , Hemostasia/efeitos dos fármacos , Argila/química , Celulose/química , Géis/química , Hemostáticos/química , Hemostáticos/farmacologia , Ratos , Hemorragia/tratamento farmacológico , Masculino , Nanotubos/química , Óxidos N-Cíclicos/química , CamundongosRESUMO
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.
Assuntos
Antibacterianos , Quitosana , Hemostasia , Hemostáticos , Staphylococcus aureus Resistente à Meticilina , Trombina , Quitosana/química , Quitosana/farmacologia , Animais , Antibacterianos/farmacologia , Antibacterianos/química , Ratos , Hemostáticos/química , Hemostáticos/farmacologia , Trombina/farmacologia , Hemostasia/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Cátions/química , Escherichia coli/efeitos dos fármacos , Masculino , PorosidadeRESUMO
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.
Assuntos
Alginatos , Bandagens , Quitosana , Liberação Controlada de Fármacos , Hemostasia , Quitosana/química , Quitosana/análogos & derivados , Alginatos/química , Hemostasia/efeitos dos fármacos , Porosidade , Animais , Sistemas de Liberação de Medicamentos , Hemostáticos/química , Hemostáticos/farmacologia , Coagulação Sanguínea/efeitos dos fármacosRESUMO
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.
Assuntos
Alginatos , Materiais Biomiméticos , Colágeno , Hemorragia , Hemostáticos , Cicatrização , Alginatos/química , Alginatos/farmacologia , Animais , Cicatrização/efeitos dos fármacos , Colágeno/química , Ratos , Hemorragia/tratamento farmacológico , Materiais Biomiméticos/química , Materiais Biomiméticos/farmacologia , Hemostáticos/farmacologia , Hemostáticos/química , Masculino , Ratos Sprague-Dawley , Hemostasia/efeitos dos fármacos , Oxirredução , Adesividade Plaquetária/efeitos dos fármacosRESUMO
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.
Assuntos
Antibacterianos , Argila , Hemostáticos , Nanopartículas Metálicas , Pseudomonas aeruginosa , Prata , Staphylococcus aureus , Antibacterianos/farmacologia , Antibacterianos/química , Prata/química , Prata/farmacologia , Hemostáticos/farmacologia , Hemostáticos/química , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/crescimento & desenvolvimento , Pseudomonas aeruginosa/efeitos dos fármacos , Nanopartículas Metálicas/química , Argila/química , Humanos , Hemostasia/efeitos dos fármacosRESUMO
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.
Assuntos
Cálcio , Hemorragia , Polimerização , Polifosfatos , Animais , Polifosfatos/química , Polifosfatos/farmacologia , Cálcio/química , Ratos , Hemorragia/prevenção & controle , Hemorragia/tratamento farmacológico , Hemostáticos/química , Hemostáticos/farmacologia , Coagulação Sanguínea/efeitos dos fármacos , Ratos Sprague-Dawley , Masculino , Hemostasia/efeitos dos fármacos , Íons/químicaRESUMO
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.
Assuntos
Fibroínas , Géis , Hemostasia , Nanofibras , Nanofibras/química , Animais , Ratos , Fibroínas/química , Fibroínas/farmacologia , Hemostasia/efeitos dos fármacos , Géis/química , Porosidade , Hemorragia/tratamento farmacológico , Fenômenos Mecânicos , Hemostáticos/química , Hemostáticos/farmacologia , Propriedades de Superfície , Água/química , Masculino , Bombyx/química , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologiaRESUMO
In an emergency, nonvariceal upper gastrointestinal bleeding (NVUGIB), endoscopic hemostasis is considered the gold standard intervention. However, current endoscopic hemostasis is very challenging to manage bleeding in large-diameter or deep lesions highly prone to rebleeding risk. Herein, a novel hemostatic peptide hydrogel (HPH) is reported, consisting of a self-assembly peptide sequence CFLIVIGSIIVPGDGVPGDG (PFV) and gelatin methacryloyl (GelMA), which can be triggered by blue laser endoscopy (BLE) for nonvariceal upper gastrointestinal bleeding treatment without recurring bleeding concerns. Upon contact with GelMA solution, PFV immediately fibrillates into ß-sheet nanofiber and solvent-induced self-assembly to form HPH gel. HPH nanofiber networks induced ultrafast coagulation by enveloping blood cells and activating platelets and coagulation factors even to the blood with coagulopathy. Besides its remarkable hemostatic performance in artery and liver injury models, HPH achieves instant bleeding management in porcine NVUGIB models within 60 s by preventing the rebleeding risk. This work demonstrates an extraordinary hemostatic agent for NVUGIB intervention by BLE for the first time, broadening potential application scenarios, including patients with coagulopathy and promising clinical prospects.
Assuntos
Hemorragia Gastrointestinal , Hemostáticos , Hidrogéis , Peptídeos , Hidrogéis/química , Animais , Hemorragia Gastrointestinal/terapia , Peptídeos/química , Hemostáticos/química , Hemostáticos/farmacologia , Suínos , Lasers , Humanos , Gelatina/química , Nanofibras/químicaRESUMO
The escalating global demand for sustainable manufacturing, motivated by concerns over energy conservation and carbon footprints, encounters challenges due to insufficient renewable materials and arduous fabrication procedures to fulfill specific requirements in medical and healthcare systems. Here, biosafe pollen cryogel is engineered as effective hemostats without additional harmful crosslinkers to treat deep noncompressible wounds. A straightforward and low-energy approach is involved in forming stable macroporous cryogel, benefiting from the unique micro-hierarchical structures and chemical components of non-allergenic plant pollen. It is demonstrated that the pollen cryogel exhibits rapid water/blood-triggered shape-memory properties within 2 s. Owing to their inherent nano/micro hierarchical structure and abundant chemical functional groups on the pollen surface, the pollen cryogel shows effective hemostatic performance in a mouse liver penetration model, which is easily removed after usage. Overall, the self-crosslinking pollen cryogel in this work pioneers a framework of potential clinical applications for the first-hand treatment on deep noncompressible wounds.
Assuntos
Criogéis , Pólen , Criogéis/química , Animais , Camundongos , Pólen/química , Hemorragia , Hemostáticos/químicaRESUMO
Acute hemorrhage is a major cause of death in many emergency cases. Although many hemostatic materials have been studied in recent years, it is still necessary to develop new hemostatic materials with remarkable efficiency, biosafety, convenient preparation, low cost, and good biodegradability. In this work, novel chitosan (CS)/ß-glycerophosphate (ß-GP) composite porous microsphere with a uniform size of 210.00 ± 2.14 µm was fabricated through water-in-water (W/W) emulsion via microencapsulation, which can avoid the use of toxic crosslink chemicals and organic solvents to achieve facile and efficient preparation of microspheres. ß-GP could promote the formation of microspheres by enhancing the hydrogen-bonding interaction between CS chains, which contributed to the macro-porous structure. Owing to their large pore size (6.0 µm) and high specific surface area (37.8 m2/g), the CS/ß-GP microspheres could absorb water quickly and adsorb protein, red blood cells, and platelets through electrostatic forces to promote blood coagulation. Furthermore, the CS/ß-GP microspheres achieved a significantly shortened hemostatic time (45 s) and reduced blood loss (0.03 g) in a rat liver injury model. Rat tail amputation test also showed a satisfactory hemostatic effect. Overall, the green and porous CS/ß-GP microspheres can be used as a facile and topical rapid hemostatic material.