Hemostatic Hydrogel Research Articles

Adhesive Hemostatic Hydrogel with Ultrafast Gelation Arrests Acute Upper Gastrointestinal Hemorrhage in Pigs

AbstractUpper gastrointestinal (GI) hemorrhage is a common clinical emergency worldwide. Endoscopic hemostasis is the current first line treatment. Nevertheless, for patients with severe active bleeding and challenging anatomy, endoscopic management can be still difficult and usually requires a higher level of surgical expertise. A simple and effective method of endoscopic hemostasis is therefore in acute clinical demand. Herein a hemostatic hybrid hydrogel comprised of hyaluronic acid and polyethylene glycol stabilized by thiourea–catechol coupling and disulfide bonds is reported. The hybrid hydrogels exhibit enhanced mechanical properties, short gelation time, and good blood clotting ability compared with fibrin gels. The in vivo hemostatic efficacy is confirmed in a rat model of arterial bleeding, in which the rapid gelation of hybrid hydrogels after topical application effectively arrests blood loss with no rebleeding occurring during resuscitation when blood pressure approximately recovers to normal. A large animal study further demonstrates the efficacy of hybrid hydrogels to achieve endoscopic hemostasis against upper GI hemorrhage in pigs. Follow‐up observations show that the hybrid hydrogels can remain adherent at the bleeding wound for 48 h, indicating the sustained hemostatic function in vivo. Collectively, this work demonstrates a promising hemostatic hydrogel for endoscopic hemostasis in upper GI hemorrhage.

Hydrogel-Based Biomaterials Engineered from Natural-Derived Polysaccharides and Proteins for Hemostasis and Wound Healing.

Rapid and effective hemostasis is of great importance to improve the quality of treatment and save lives in emergency, surgical practice, civilian, and military settings. Traditional hemostatic materials such as tourniquets, gauze, bandages, and sponges have shown limited efficacy in the management of uncontrollable bleeding, resulting in widespread interest in the development of novel hemostatic materials and techniques. Benefiting from biocompatibility, degradability, injectability, tunable mechanical properties, and potential abilities to promote coagulation, wound healing, and anti-infection, hydrogel-based biomaterials, especially those on the basis of natural polysaccharides and proteins, have been increasingly explored in preclinical studies over the past few years. Despite the exciting research progress and initial commercial development of several hemostatic hydrogels, there is still a significant distance from the desired hemostatic effect applicable to clinical treatment. In this review, after elucidating the process of biological hemostasis, the latest progress of hydrogel biomaterials engineered from natural polysaccharides and proteins for hemostasis is discussed on the basis of comprehensive literature review. We have focused on the preparation strategies, physicochemical properties, hemostatic and wound-healing abilities of these novel biomaterials, and highlighted the challenges that needed to be addressed to achieve the transformation of laboratory research into clinical practice, and finally presented future research directions in this area.

Poly(N-vinyl imidazole) Cross-Linked β-Cyclodextrin Hydrogel for Rapid Hemostasis in Severe Renal Arterial Hemorrhagic Model.

A unique facile process has been adopted for fast assembly of a poly(N-vinyl imidazole) cross-linked β-cyclodextrin hydrogel through microwave-assisted free radical polymerization, using N,N'-methylenebis(acrylamide) cross-linker. The copolymer possesses positive surface charge, one of the characteristic properties of an ideal hemostatic hydrogel. The functionalized imidazole-based hydrogel demonstrates rapid, superior blood coagulation kinetics under in vitro and in vivo conditions. On application to a major renal arterial hemorrhagic model, this hydrogel shows better blood clotting kinetics, leading to complete hemostasis in as few as ∼144 ± 7 s. Additionally, 350 μL of whole blood was clotted instantly, in ∼35 s, and therefore, reinforcing its hemostatic potential. The hydrogel demonstrates excellent biocompatibility, when seeded with human dermal fibroblast cells, retaining the native property of its predecessor. In addition, the hydrogel presents excellent hemocompatibility when tested with whole blood with the highest hemolytic ratio of 1.07 ± 0.05%. Moreover, it also demonstrates potential as a carrier for sustained release of an anesthetic drug, lidocaine hydrochloride monohydrate (∼83% in 24 h). The rapid hemostatic behavior of the hydrogel is coupled with its cytocompatibility and hemocompatibilty properties along with controlled drug release characteristics. These behaviors evidently demonstrate it to be an excellent alternative for a superior hemostatic material for severe hemorrhagic conditions.

An injectable anti-microbial and adhesive hydrogel for the effective noncompressible visceral hemostasis and wound repair

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 -NH2 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.

An injectable, dual crosslinkable hybrid pectin methacrylate (PECMA)/gelatin methacryloyl (GelMA) hydrogel for skin hemostasis applications

Biomaterials for effective hemorrhage control are urgently needed in clinics as uncontrolled bleeding is associated with high mortality. Herein, we developed an injectable and in situ photo-crosslinkable hybrid hemostatic hydrogel by combining pectin methacrylate (PECMA) and gelatin methacryloyl (GelMA). This modular material system combines ionic- and photo-crosslinking chemistries to design interpenetrating networks (IPN) exhibiting tunable rheology, highly porous structure, and controllable swelling and mechanical properties. By simply changing the calcium (0–15 mM) and polymer (1.5–7%) content used for the sequential crosslinking of hydrogels via calcium gelation and UV-photopolymerization, it was possible to precisely modulate the injectability, degradation, and swelling ratio. Moreover, it is demonstrated that PECMA/GelMA hydrogels present good cytocompatibility and uniquely synergize the hemostatic properties of calcium ions on PECMA, the amine residues on GelMA, and the highly porous network toward rapid blood absorption and fast coagulation effect. An in vitro porcine skin bleeding model confirmed that the hydrogel could be directly injected into the wound and rapidly photo-crosslinked, circumventing the bleeding and decreasing the coagulation time by 39%. Importantly, the crosslinked hydrogel could be easily removed to prevent secondary wound injury. Overall, this injectable hybrid PECMA/GelMA hydrogel stands as a promising hemostatic material.

Mussel-inspired adhesive antioxidant antibacterial hemostatic composite hydrogel wound dressing via photo-polymerization for infected skin wound healing

With the increasing prevalence of drug-resistant bacterial infections and the slow healing of chronically infected wounds, the development of new antibacterial and accelerated wound healing dressings has become a serious challenge. In order to solve this problem, we developed photo-crosslinked multifunctional antibacterial adhesive anti-oxidant hemostatic hydrogel dressings based on polyethylene glycol monomethyl ether modified glycidyl methacrylate functionalized chitosan (CSG-PEG), methacrylamide dopamine (DMA) and zinc ion for disinfection of drug-resistant bacteria and promoting wound healing. The mechanical properties, rheological properties and morphology of hydrogels were characterized, and the biocompatibility of these hydrogels was studied through cell compatibility and blood compatibility tests. These hydrogels were tested for the in vitro blood-clotting ability of whole blood and showed good hemostatic ability in the mouse liver hemorrhage model and the mouse-tail amputation model. In addition, it has been confirmed that the multifunctional hydrogels have good inherent antibacterial properties against Methicillin-resistant Staphylococcus aureus (MRSA). In the full-thickness skin defect model infected with MRSA, the wound closure ratio, thickness of granulation tissue, number of collagen deposition, regeneration of blood vessels and hair follicles were measured. The inflammation-related cytokines (CD68) and angiogenesis-related cytokines (CD31) expressed during skin regeneration were studied. All results indicate that these multifunctional antibacterial adhesive hemostatic hydrogels have better healing effects than commercially available Tegaderm™ Film, revealing that they have become promising alternative in the healing of infected wounds.

Hemostatic Self-Healing Hydrogel with Excellent Biocompatibility Composed of Polyphosphate-Conjugated Functional PNIPAM-Bearing Acylhydrazide.

Biocompatible self-healing hydrogels present an effective application as drug-releasing vehicles for tissue engineering and wound repairing. At the same time, the effective hemostatic property of the hydrogels also improves the application property as wound dressing materials. In this research, the PNIPAM-bearing acylhydrazide P(NIPAM-co-AH) was synthesized and then hemostatic polyphosphate (PolyP) was imported to prepare polyphosphate-conjugated P(NIPAM-co-AH) (PNAP). Through the acylhydrazone connection of PNAP and aldehyde functional PEO (PEO DA), the self-healing hydrogel with a hemostatic property was fabricated with good flexibility and sealing effect. The resultant hydrogels kept excellent biocompatibility and showed controlled drug release behavior. More importantly, the hydrogel accelerated the coagulation rate in vitro and presented a strong hemostatic effect as the binder in the hemorrhage model in vivo, which endow the hemostatic hydrogel with a very useful drug delivery carrier for wound healing applications or first aid treatment of the wounded in critical situations.

Hemostatic performance of chitosan-based hydrogel and its study on biodistribution and biodegradability in rats

Hemostasis is of great significance regardless of the smooth operation or postoperative recovery. Therefore, it is urgent to develop a hemostatic material with excellent biodegradability and biocompatibility. It is well known that both carboxymethyl chitosan and hyaluronic acid with biodegradability and biocompatibility have wound healing promoting property. Here, a degradable chitosan-based hydrogel was prepared based on carboxymethyl chitosan and cross-linked by oxidized hyaluronic acid. The hemostatic performance of the hydrogel in rat liver resection injury was evaluated which results showed that the hydrogel exhibited comparable hemostatic properties compared with Fibrin Sealant. In addition, the hydrogel proved to be rapidly absorbed by the body without significant accumulation in vivo, demonstrating good biodegradability and biocompatibility. The overall results suggested the hydrogel will be a promising hemostatic hydrogel for controlling bleeding.

Thermoresponsive Hemostatic Hydrogel with a Biomimetic Nanostructure Constructed from Aggregated Collagen Nanofibers

Uncontrollable bleeding poses considerable fatality risks by large-volume blood losses. Current emergency antibleeding handlings including either compression with gauze or "passive" blood transfusion are thus far from ideal, while most recently developed hemostatic agents still share common limitations without considering the subsequent tissue repairing and antibacterial activity after treatment. Herein, we introduce a novel bioinspired aggregated collagen nanofiber-based biocompatible and efficient hemostatic hydrogel material (TS-Gel-Ag-col) prepared by the integration of multifunctional compounds of muco-mimetic poloxamer, polyvinylpyrrolidone, and dencichine/chitosan dialdehyde synergistic crosslinked aggregated collagen nanofibers decorated with silver nanoparticles. Comprehensive material characterization and in vitro and in vivo studies of TS-Gel-Ag-col demonstrate that these materials possess effective antihemorrhagic and antibacterial wound protection effects. Moreover, TS-Gel-Ag-col can facilitate the tissue repairing of skin wounds by promoting revascularization. TS-Gel-Ag-col holds great promise for next-generation collagen-based absorbable hemostatic materials and for the development of smart artificial skins.

Polymeric Hydrogel Systems as Emerging Biomaterial Platforms to Enable Hemostasis and Wound Healing

Broad interest in developing new hemostatic technologies arises from unmet needs in mitigating uncontrolled hemorrhage in emergency, surgical, and battlefield settings. Although a variety of hemostats, sealants, and adhesives are available, development of ideal hemostatic compositions that offer a range of remarkable properties including capability to effectively and immediately manage bleeding, excellent mechanical properties, biocompatibility, biodegradability, antibacterial effect, and strong tissue adhesion properties, under wet and dynamic conditions, still remains a challenge. Benefiting from tunable mechanical properties, high porosity, biocompatibility, injectability and ease of handling, polymeric hydrogels with outstanding hemostatic properties have been receiving increasing attention over the past several years. In this review, after shedding light on hemostasis and wound healing processes, the most recent progresses in hydrogel systems engineered from natural and synthetic polymers for hemostatic applications are discussed based on a comprehensive literature review. Most studies described used in vivo models with accessible and compressible wounds to assess the hemostatic performance of hydrogels. The challenges that need to be tackled to accelerate the translation of these novel hemostatic hydrogel systems to clinical practice are emphasized and future directions for research in the field are presented.

Injectable, self-healing, antibacterial, and hemostatic N,O-carboxymethyl chitosan/oxidized chondroitin sulfate composite hydrogel for wound dressing.

Biodegradable and injectable hydrogels derived from natural polysaccharides have attracted extensive attention in biomedical applications due to their minimal invasiveness and ability to accommodate the irregular wound surfaces. In this work, we report the development of an in-situ-injectable, self-healing, antibacterial, hemostatic, and biocompatible hydrogel derived from the hybrid of N,O-carboxymethyl chitosan (N,O-CMC) and oxidized chondroitin sulfate (OCS), which did not require any chemical crosslinking. The N,O-CMC/OCS hydrogel could be readily produced under physiological conditions by varying the N,O-CMC-to-OCS ratio, relying on the Schiff base reaction between the -NH- functional groups of N,O-CMC and the -CHO functional groups of OCS. The results showed that the N,O-CMC2/OCS1 hydrogel had relatively long gelation time (133s) and stable performances. The viability of NIH/3T3 cells and endothelial cells cultured with the N,O-CMC2/OCS1 hydrogel extract was roughly 85%, which demonstrated its low cell toxicity. Besides, the N,O-CMC2/OCS1 hydrogel revealed excellent antibacterial properties due to the inherent antibacterial ability of N,O-CMC. Importantly, the hydrogel tightly adhered to the biological tissue and demonstrated excellent in vivo hemostatic performance. Our work describing an injectable, self-healing, antibacterial, and hemostatic hydrogel derived from polysaccharides will likely hold good potential in serving as an enabling wound dressing material.

Pulp regeneration with hemostatic matrices as a scaffold in an immature tooth minipig model

Control of blood clotting in root canal systems is one of the most critical and difficult concerns for regenerative endodontics therapy (RET). The purpose of this study was to investigate the effects of using gelatin- and fibrin-based hemostatic hydrogels as a scaffold on pulp regeneration in a minipig model. Cell viability of human dental pulp stem cells cultured three-dimensionally in gelatin-based and fibrin-based scaffolds was evaluated by MTT and live/dead assay. RET was performed on 24 immature premolars with an autologous blood clot (PC), gelatin-based and fibrin-based hemostatic matrices (GM and FM), or without the insertion of a scaffold (NC). The follow-up period was 12 weeks. Radiographic and histologic assessments for pulp regeneration were performed. Gelatin-based scaffolds exhibited significantly higher cell viability than fibrin-based scaffolds after 15 days (P < 0.05). The PC and GM groups showed favorable root development without inflammation and newly mineralized tissue deposited in the root canal system, while FM group presented inflammatory changes with the continuation of root development. The NC group exhibited internal root resorption with periapical lesions. The application of GM in RET led to favorable clinical outcomes of root development without inflammatory changes compared to conventional RET. Our results suggest that GM may serve as a viable regenerative scaffold for pulp regeneration.

Thermoresponsive Chitosan/DOPA-Based Hydrogel as an Injectable Therapy Approach for Tissue-Adhesion and Hemostasis.

Chitosan (CS) hydrogels are widely used in wound hemostatic agents due to their superior biocompatibility, biodegradability, and hemostatic effect. However, most of them fail to achieve great hemostatic effect because of poor adhesion to bleeding tissues. Also, the conventional implantation surgery of hemostatic hydrogels to internal bleeding wounds may cause secondary trauma to the human body. In this work, catechol-hydroxybutyl chitosan (HBCS-C) has been designed and prepared by grafting hydroxybutyl groups and catechol groups to the CS backbones. The multifunctional HBCS-C hydrogels are fabricated with the properties of thermosensitivity, injectability, tissue-adhesion, biodegradation, biocompatibility, and wound hemostasis. They exhibit excellent liquid-gel transition at different temperatures, through the changes of hydrophilic-hydrophobic interaction and hydrogen bonds generating from hydroxybutyl groups. By the multiple interactions between catechol groups/amino groups and tissues, the biocompatible hydrogels can strongly adhere on the surface of tissue. To further study, the bleeding rat-liver models are made to evaluate the hemostatic effects. After injecting the hydrogel precursor solution into the rat body, the hydrogels are not only formed in situ within 30 s but are also firmly adhered to the bleeding tissues which shows effective hemostasis. The injectability and tissue-adhesion improvement in this study gives a new insight into hemostatic agents, and the multifunctional hydrogels have a great potential in the biomedical application.

Tough polyacrylamide-tannic acid-kaolin adhesive hydrogels for quick hemostatic application.

Adhesive hydrogels for wet and dynamic tissues are important for biomedical applications in order to withstand cyclic loading such as in the case of hemorrhaging control on the curved skins and heart tissues. However, the fabrication of hydrogels with strong mechanical properties, high adhesion strength, and hemostatic efficiency remains a big challenge. Inspired by the great adhesive behavior of mussels and Arion subfuscus, novel adhesive and hemostatic polyacrylamide-tannic acid-kaolin (PAAm-TA-KA) hydrogels were reported in this work. The hydrogels displayed high strength and toughness due to their physical and chemical crosslinking structures. The abundant catechol groups on tannic acid endow the hydrogels with strong and durable adhesion strength of up to 500kPa on porcine skin. When applied onto human skin, the hydrogels could be easily peeled off without leaving any remains and causing any damages. The kaolin nanoparticles incorporated in the PAAm-TA-KA hydrogels not only served as a physical crosslinking agent, but an activator of the blood clotting factor FXII for accelerating the formation of thrombus. The strong tissue adhesion and blood coagulant potential of the PAAm-TA-KA hydrogels imparted them high hemostatic efficiency. The free-standing, adhesive, tough, cytocompatible, and hemostatic hydrogels are highly promising for traumatic bleeding control materials.

Absorbable hemostatic hydrogels comprising composites of sacrificial templates and honeycomb-like nanofibrous mats of chitosan

The development of hemostatic technologies that suit a diverse range of emergency scenarios is a critical initiative, and there is an increasing interest in the development of absorbable dressings that can be left in the injury site and degrade to reduce the duration of interventional procedures. In the current study, β-cyclodextrin polyester (CDPE) hydrogels serve as sacrificial macroporous carriers, capable of degradation under physiological conditions. The CDPE template enables the assembly of imprinted chitosan honeycomb-like monolithic mats, containing highly entangled nanofibers with diameters of 9.2 ± 3.7 nm, thereby achieving an increase in the surface area of chitosan to improve hemostatic efficiency. In vivo, chitosan-loaded cyclodextrin (CDPE-Cs) hydrogels yield significantly lower amounts of blood loss and shorter times to hemostasis compared with commercially available absorbable hemostatic dressings, and are highly biocompatible. The designed hydrogels demonstrate promising hemostatic efficiency, as a physiologically-benign approach to mitigating blood loss in tissue-injury scenarios.

Toxicity-Attenuated Glycol Chitosan Adhesive Inspired by Mussel Adhesion Mechanisms.

Chitosan-catechol, inspired from mussel-adhesive-proteins, is characterized by the formation of an adhesive membrane complex through instant bonding with serum proteins not found in chitosan. Using this intrinsic property, chitosan-catechol is widely applied for hemostatic needles, general hemostatic materials, nanoparticle composites, and 3D printing. Despite its versatility, the practical use of chitosan-catechol in the clinic is limited due to its undesired immune responses. Herein, a catechol-conjugated glycol chitosan is proposed as an alternative hemostatic hydrogel with negligible immune responses enabling the replacement of chitosan-catechol. Comparative cellular toxicity and in vivo skin irritation between chitosan-catechol and glycol chitosan-catechol are evaluated. Their immune responses are also assessed using histological analysis after subcutaneous implantation into mice. The results show that glycol chitosan-catechol significantly attenuates the immune response compared with chitosan-catechol; this finding is likely due to the antibiofouling effect of ethylene glycol groups and the reduced adhesion of immune cells. Finally, the tissue adhesion and hemostatic ability of glycol chitosan-catechol hydrogels reveal that these ethylene glycol groups do not dramatically modify the adhesiveness and hemostatic ability compared with nonglycol chitosan-catechol. This study suggests that glycol chitosan-catechol can be a promising alternative to chitosan-catechol in various biomedical fields such as hemostatic agents.

A strongly adhesive hemostatic hydrogel for the repair of arterial and heart bleeds

Uncontrollable bleeding is a major problem in surgical procedures and after major trauma. Existing hemostatic agents poorly control hemorrhaging from traumatic arterial and cardiac wounds because of their weak adhesion to wet and mobile tissues. Here we design a photo-reactive adhesive that mimics the extracellular matrix (ECM) composition. This biomacromolecule-based matrix hydrogel can undergo rapid gelling and fixation to adhere and seal bleeding arteries and cardiac walls after UV light irradiation. These repairs can withstand up to 290 mm Hg blood pressure, significantly higher than blood pressures in most clinical settings (systolic BP 60–160 mm Hg). Most importantly, the hydrogel can stop high-pressure bleeding from pig carotid arteries with 4~ 5 mm-long incision wounds and from pig hearts with 6 mm diameter cardiac penetration holes. Treated pigs survived after hemostatic treatments with this hydrogel, which is well-tolerated and appears to offer significant clinical advantage as a traumatic wound sealant.

Tunichrome-inspired pyrogallol functionalized chitosan for tissue adhesion and hemostasis

The nature-inspired fabrication of tissue adhesive and hemostatic hydrogels holds great potential for restoring damaged internal tissue in regenerative medicine. However, feeble adhesion, multifaceted systems, prohibitive costs, and toxicity impede their applications in the medical field. In order to solve this problem, we fabricated chitosan-based wet tissue adhesive with hemostatic functions inspired by the self-healing mechanism of the tunicate. In order to introduce pyrogallol moiety, gallic acids, which are broadly distributed in nature, were incorporated into chitosan backbone, a key residue for the self-healing process of tunichrome in tunicates. The in vitro adhesion test results of the tunicate-inspired hydrogel exhibited two-fold greater adhesion ability in wet condition than did fibrin glue, a commercially available surgical glue. Further, the tunicate-inspired hydrogel exhibited significantly more platelet adhesion and blood clotting ability than the parent polymer. We also demonstrated the ability of the derivative to completely mimic the tunicate’s fibrous structure by fabricating an electrospun mat. The hemostatic function vis-à-vis the wet adhesiveness of the synthesized chitosan-based material may be useful for facilitating the shortcomings of the restorative tissue medicine. Additionally, the electrospinning capability will enable the modulate of the structure-property relationship and a three-dimensional design for its application site.

Injectable Hemostat Composed of a Polyphosphate-Conjugated Hyaluronan Hydrogel.

We have developed a new hydrogel hemostat composed of hyaluronan (HA) conjugated with inorganic polyphosphate (PolyP). A hemostatic hydrogel, HAX-PolyP, was formed rapidly by mixing aldehyde-modified HA and hydrazide-modified HA conjugated with PolyP (HA-PolyP). Although the gelation rate decreased with increasing PolyP content, the gelation time was below 5 min. In addition, the hydrogel swelling volume decreased with increasing PolyP content, but the degradation rate did not depend on PolyP content and the hydrogel underwent complete degradation through hydrolysis over 3 weeks in phosphate buffered saline. HAX-PolyP showed similar biocompatibility with the HA hydrogel without PolyP conjugation in vitro and in vivo. Intraperitoneal administration of HAX-PolyP did not induce any adhesion in the peritoneum and clot formation in the lungs. Finally, HA-PolyP accelerated the coagulation rate of human plasma ex vivo, and HAX-PolyP showed as strong a hemostatic effect as fibrin glue in a mouse liver bleeding model in vivo.

Antibacterial and hemostatic hydrogel via nanocomposite from cellulose nanofibers

Bacterial infection and uncontrolled bleeding are the major challenges facing the wound treatment. In order to solve these problems, we have devised a green nanocomposite hydrogel by introducing the aminated silver nanoparticles (Ag-NH2 NPs) and gelatin (G) to carboxylated cellulose nanofibers (CNF). Interpenetrating polymeric network (IPN) was formed by interaction of multicomponent, leading to the non-covalent (dynamic ionic bridges) crosslinked hydrogel CNF/G/Ag. The produced hydrogel dressing with 0.5 mg/mL Ag-NH2 NPs (CNF/G/Ag0.5) demonstrated stronger mechanical, self-recovery, antibacterial properties, satisfactory hemostatic performance, and appropriate balance of fluids on the wound bed (2093.9 g/m2 per day). More importantly, the wound healing model evaluation in vitro and in vivo of CNF/G/Ag0.5 showed an outstanding biocompatibility (∼100% infected cell viability) and wound healing efficacy (∼90% healed and 83.3% survival after 14 days). Our study paved a highly promising approach to improve the performance of cellulose-based hydrogel dressing and would also be useful for developing ideal skin wound dressings by other green materials.