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Introduction: Immediate control of bleeding and anti-infection play important roles in wound management. Multiple organ dysfunction syndrome and death may occur if persistent bleeding, hemodynamic instability, and hypoxemia are not addressed. The combination of clay and hydrogel provides a new outlet for wound hemostasis. In this review, the current research progress of hydrogel/clay composite hemostatic agents was reviewed., Areas Covered: This paper summarizes the characteristics of several kinds of clay including kaolinite, montmorillonite, laponite, sepiolite, and palygorskite. The advantages and disadvantages of its application in hemostasis were also summarized. Future directions for the application of hydrogel/clay composite hemostatic agents are presented., Expert Opinion: Clay can activate the endogenous hemostatic pathway by increasing blood cell concentration and promoting plasma absorption to accelerate the hemostasis. Clay is antimicrobial due to the slow release of metal ions and has a rich surface charge with a high affinity for proteins and cells to promote tissue repair. Hydrogels have some properties such as good biocompatibility, strong adhesion, high stretchability, and good self-healing. Despite promising advances, hydrogel/clay composite hemostasis remains a limitation. Therefore, more evidence is needed to further elucidate the risk factors and therapeutic effects of hydrogel/clay in hemostasis and wound healing.

The design of new hemostatic materials to mitigate uncontrolled bleeding in emergencies is challenging. Chitosan-based hemostatic hydrogels have frequently been used for hemostasis due to their unique biocompatibility, tunable mechanical properties, injectability, and ease of handling. Moreover, chitosan (CS) absorbs red blood cells and activates platelets to promote hemostasis. Benefiting from these desired properties, the hemostatic application of CS hydrogels is attracting ever-increasing research attention. This paper reviews the recent research progress of CS-based hemostatic hydrogels and their advantageous characteristics compared to traditional hemostatic materials. The effects of the hemostatic mechanism, effects of deacetylation degree, relative molecular mass, and chemical modification on the hemostatic performance of CS hydrogels are summarized. Meanwhile, some typical applications of CS hydrogels are introduced to provide references for the preparation of efficient hemostatic hydrogels. Finally, the future perspectives of CS-based hemostatic hydrogels are presented. [ABSTRACT FROM AUTHOR]

Wound healing is a long-term and complex biological process that involves multiple hemostasis, inflammation, proliferation, and remodeling stages. In order to realize comprehensive and systematic wound management, appropriate wound treatment bio-adhesives are urgently needed. Hydrogel bio-adhesives have excellent properties and show unique and remarkable advantages in the field of wound management. This review begins with a detailed description of the design criteria and functionalities of ideal hydrogel bio-adhesives for wound healing. Then, recent advances in polysaccharide-based multifunctional hydrogel bio-adhesives, which involve chitosan, hyaluronic acid, alginate, cellulose, dextran, konjac glucomannan, chondroitin sulfate, and other polysaccharides, are comprehensively discussed. Finally, the current challenges and future research directions of polysaccharide-based hydrogel bio-adhesives for wound healing are proposed to stimulate further exploration by researchers. [ABSTRACT FROM AUTHOR]

Currently, hydrogels are widely studied for wound dressings. However, wound healing is often hindered by bacterial infection. In this study, in situ cross-linked carboxymethyl chitosan (CMCS)/oxidized dextran (OD)/poly-γ-glutamic acid (γ-PGA) (COP) hydrogel was prepared for antimicrobial and hemostasis of diffuse wounds. In the COP hydrogel, γ-PGA was able to drain the surface moisture of the wound to enhance the surface adhesion. Moreover, γ-PGA could concentrate blood by absorbing plasma, and CMCS could electrostatically adsorb negative RBCs. The antibacterial properties of CMCS and OD endowed the COP hydrogel with certain antibacterial effects. In the inhibition zone experiment, an obvious inhibition zone appeared around the COP hydrogel. In vivo studies showed that the COP hydrogel significantly inhibited bacterial growth and promoted wound healing. In the rat tail diffuse hemorrhage wound model, the COP hydrogel showed superior hemostasis ability. Therefore, the multifunctional COP hydrogel is expected to find different applications in wound hemostasis and healing. [ABSTRACT FROM AUTHOR]

Massive bleeding is a great threat to the life safety of patients, which is a challenging clinical problem. Therefore, it is urgent to develop a kind of multifunctional dressing material with hemostatic ability and antibacterial performance to promote wound healing and repair. To resolve this issue, in this study, a carboxymethyl chitosan (CMCS)/sodium alginate (SA)/oxidized dextran (ODE) (CSO) multifunctional hydrogel was developed. The hydrogel could rapidly gel through Schiff base reaction and amide reaction and firmly adhere to the skin at the wound, to realize the fast hemostasis. Importantly, it was verified that the hydrogel could prevent the Staphylococcus aureus -caused wound infection, owing to the antibacterial effect of CMCS and ODE. In addition, the CSO hydrogel had good water retention capacity and was able to mimic the three-dimensional structure of the natural extracellular matrix, thereby promoting wound repair in mice. In vitro whole-blood clotting assay demonstrated that red blood cells could be adhered to the surface of hydrogel, showing good hemostasis in rat liver injury and tail amputation models. Together with the biocompatible feature, CSO hydrogel holds a great application prospect in hemostasis and wound healing. • Carboxymethyl chitosan/sodium alginate/oxidized dextran hydrogel was prepared. • The hydrogel had excellent adhesion, mechanical properties and biodegradability. • The hydrogel could firmly adhere to the skin at the wound. • The hydrogel reduced the blood loss on rat liver injury and tail bleeding models. [ABSTRACT FROM AUTHOR]

Benefiting from the biocompatibility, adhesiveness, and natural extracellular matrix-mimicking ability, hydrogels have received increasing research in recent years. In this study, a hydrogel system composed of dopamine, quaternized ammoniated chitosan (QCS), and polyvinylpyrrolidone was reported to exhibit fast hemostatic properties in Sprague-Dawley rat tail amputation and liver bleeding models. The results showed that this hydrogel had good hemostatic properties. The designed hydrogel showed high swelling ratios in H 2 O, PBS, and 0.9 % NaCl solution, indicating its capability to absorb tissue residual exudate and form a stable hydrogel. Compared with the control group, the blood loss in Sprague-Dawley rat tail amputation and liver bleeding were reduced by nearly 78 % and 76 %, respectively. Interestingly, dopamine endowed the hydrogel with antioxidant properties, thus holding a great application promise in inflammatory wounds. Furthermore, the designed hydrogel demonstrated good and reversible adhesion properties (12.23 ± 0.22 kPa–24.31 ± 0.55 kPa), ensuring its firm attachment to bleeding wounds of pig skin in wet environments. This research points out a novel path for designing chitosan-based hydrogels for biomedical applications. [Display omitted] • A hydrogel composed of dopamine, quaternized ammoniated chitosan, and polyvinylpyrrolidone was reported. • This hydrogel had excellent hemostatic properties. • Dopamine endowed the hydrogel with antioxidant properties. • The hydrogel demonstrated excellent and reversible adhesion properties. [ABSTRACT FROM AUTHOR]

The rapid and effective hemostasis of gastrointestinal bleeding sites remains an urgent clinical challenge. In this study, an ultrafast self-gelling, sprayable, and adhesive carboxymethyl chitosan/poly-γ-glutamic acid/oxidized dextran (CPO) powder was designed for gastric perforation hemostasis and healing. When the CPO powder was sprayed to the gastric perforation site, the CPO powder absorbed water from the blood and concentrate blood cells and clotting factors to achieve the purpose of rapid hemostasis. During the hemostasis, the CPO powder formed a hydrogel in situ through the formation of amide bonds and Schiff base bonds within 15 s, forming a physical barrier to cover the wound surface. Concurrently, the aldehyde group (-CHO) of oxidized dextran formed additional Schiff base bonds with the amino group (−NH 2) of the tissue, enabling the CPO powder with wound surface adhesion. Moreover, the CPO powder was shown to have excellent in vitro and in vivo antibacterial properties and it was able to promote the healing of infected wounds in a mouse model. In summary, CPO powder provides a promising idea for the rational design of gastrointestinal hemostatic agents. [ABSTRACT FROM AUTHOR]

Stopping bleeding at an early stage and promoting wound healing are of great significance for efficient wound management. In this study, a carboxymethyl chitosan (CMCS)/poly-γ-glutamic acid (γ-PGA)/platelet-rich plasma (PRP) hydrogel (CP-PRP hydrogel) was firstly prepared by crosslinking of CMCS with γ-PGA and the enzymatic coagulation of PRP. Then, the CP-PRP hydrogel was freeze-dried and transformed into a sponge (CP-PRP sponge). A series of safety experiments with cells, blood, and tissues proved the biocompatibility of the CP-PRP sponge. Importantly, the CP-PRP sponge was able to adhere and condense red blood cells, which accelerated blood clotting. Therefore, the CP-PRP sponge showed an enhanced hemostasis effect compared to SURGIFLO® Hemostatic Matrix. Moreover, in vitro and in vivo experiments showed that the sponge was able to release epidermal growth factor (EGF) and vascular endothelial growth factor (VEGF). Thus, in a mouse model of full-thickness skin defects, the wounds of the sponge-treated mice were significantly healed within two weeks. These results proved the transforming potential of the CP-PRP sponge as a novel bioactive wound dressing. [ABSTRACT FROM AUTHOR]

The conventional method of using montmorillonite hemostatic materials affects the hemostatic effect due to easy dislodgement on the wound surface. In this paper, a multifunctional bio-hemostatic hydrogel (CODM) was prepared based on hydrogen bonding and Schiff base bonding using modified alginate, polyvinylpyrrolidone (PVP), and carboxymethyl chitosan. The amino group-modified montmorillonite was uniformly dispersed in the hydrogel by its amido bond formation with the carboxyl groups of carboxymethyl chitosan and oxidized alginate. The catechol group, –CHO, and PVP can form hydrogen bonds with the tissue surface to afford the firm tissue adhesion to afford the wound hemostatic. The addition of montmorillonite-NH 2 further improves the hemostatic ability, making it better than commercial hemostatic materials. Moreover, the photothermal conversion ability (derived from the polydopamine) was synergized with the phenolic hydroxyl group, quinone group, and the protonated amino group to effectively kill the bacteria in vitro and in vivo. Based on its in vitro and in vivo biosafety and satisfactory degradation ratio anti-inflammatory, antibacterial, and hemostatic properties, the CODM hydrogel holds promising potential for emergency hemostasis and intelligent wound management. [ABSTRACT FROM AUTHOR]

Hydrogel is a kind of hemostatic agent with good application prospect. However, the water molecules on the wound made the hydrogel less adhesive to wet wound tissue. Herein, the carboxymethyl chitosan (CMCS)/oxidized dextran (OD)/γ-polyglutamic acid (γ-PGA) hydrogel was prepared using a double-barreled syringe for hemostasis of diffuse and incompressible wound bleeding. The hydrogel formation was based on the intramolecular lactam bonds, intermolecular amide bonds, and Schiff base bonds. In the hydrogel, the super hydrophilic γ-PGA could drain the surface moisture of the wound and create a local dry environment for enhanced surface adhesion. In vivo study showed that the CMCS/ODex/γ-PGA hydrogel possesses a good biosafety and biodegradability. Interestingly, the CMCS/ODex/γ-PGA hydrogel exhibited excellent hemostatic abilities in dynamic humid environment and resisted a high blood pressure of 238 mmHg, which exceeds the threshold systolic blood pressure of healthy adults (i.e. , 120 mmHg). Together with the antibacterial and reactive nitrogen species scavenging activities, this study is expected to provide a new method to design the wet-surface adhesives for the efficient hemostatic application. [Display omitted] [ABSTRACT FROM AUTHOR]

An in-situ formed hemostatic hydrogel (GelMA/OD/Borax) was prepared for the emergency wound hemostasis and anti-inflammation applications. Gelatin was chosen as the backbone and modified with methacrylic anhydride (MA) to synthesize GelMA, which showed the admirable UV light activatable polymerizing ability. Aldehyde groups, which cross-linked with the -NH 2 on the tissue surface and afforded the tissue adhesion, were produced by oxidizing the o-hydroxyl groups of dextran. Further, the sodium tetraborate formed dynamic boric acid ester bonds with the oxidized dextran (OD). With this triple-network structure, the as-prepared hydrogel presented excellent hemostatic capacity and surmounted a high blood pressure of 165 mmHg, which is higher than the threshold systolic blood pressure of healthy adults (i.e., 120 mmHg). The mechanical property, morphology, biocompatibility and degradation of the hydrogel were character Borax, the hydrogel successfully blocked the bleeding and accelerated the wound healing. This research provides a new modality for the design of a multifunctional hemostatic hydrogel for effective hemostasis and wound healing. • GelMA/OD/Borax hydrogel is reported for the wound hemostasis and anti-inflammation. • The hemostatic hydrogel can surmount a high blood pressure of 165 mmHg. • The hydrogel is biocompatible, degradable, and has a good antibacterial capacity. • The hydrogel can accelerate the wound healing. [ABSTRACT FROM AUTHOR]