Major bioactivities include the promotion of wound healing, haemostatic activity, immunity enhancement, hypolipidemic activity, mucoadhesion, and antimicrobial activity.

Despite its low water solubility, chitosan has become a common substance in biomaterials research and has been used for several applications in the biomedical field. The soft, non-woven CF dressing is made of chitosan fibres that can accelerate haemostasis and wound care during arterial hemorrhage.

With its unique flexibility, the CF dressing is suitable for various wound surfaces, regardless of location, size, sinus, or depth. Chitosan fibre manufacturing techniques have been established during the past two decades. Generally, CF dressing is prepared using a wet-spinning process that produces fibres by dissolving the polymer in a solvent e.

acetic acid , after which the polymer solution is extruded via dies into a non-solvent e. aqueous sodium hydroxide. The polymer precipitate emerges in the form of fibres that can be washed, drained, and dried. The CF dressing uses the properties of chitosan fibres to combine an adequate porous structure with excellent degradability and mechanical properties.

The CS dressing, which is a light-yellow sponge, is made of natural organic chitosan particles and can be comfortably attached to the skin to seal a wound.

Generally, CS dressing is prepared using a freeze-drying method, resulting in a sponge-like form. It keeps the wound sterile for as long as seven days. Additionally, the porosity of the CS dressing allows rapid absorption of a large volume of exudate from the injury site.

Following absorption, the exudate interacts with the CS dressing to form a moist environment covering the wound for up to seven days. This study aims to compare the efficacy of chitosan-based dressings and commercial gauze in a swine model. We explored the potential of these two chitosan-based dressings to minimize femoral artery hemorrhage and achieve immediate haemostasis in a swine model.

Based on our results, chitosan-based dressings require further study as alternatives to traditional dressings in pre-hospital emergency care. The present study shows that the CF and CS dressings achieved haemostasis effectively, rapidly controlling moderate-to-severe hemorrhage, which represented a great improvement over commercial gauze.

The reduced bleeding time resulted in less blood loss and a lower fluid resuscitation rate. It is reasonable to postulate that the large blood loss with commercial gauze, and the subsequent high fluid resuscitation rate, reduced the clotting. capacity of the blood, leading to unfavorable outcomes.

Both chitosan-based dressings exhibited similar efficacy even in the presence of anticoagulants in the blood. Therefore, we hypothesize that interactions between the positively charged ions in the chitosan and the negatively charged ions in red blood cell membranes may enhance haemagglutination and encourage platelet adhesion and activation via protein adsorption and orientation, thus affecting cellular responses to proteins 14, It has also been demonstrated that the porosity of this dressing facilitates higher ventilation over the injury site, allowing more oxygen to diffuse inward across the skin, thereby stimulating the healing process.

If attached to the surface of the chitosan-based dressing, the metal cation—chitosan complex enhances the adhesion of erythrocytes and platelets to the injury site. Chitosan also improves blood coagulation efficiency either stopping bleeding or controlling hemorrhage.

Once the bleeding has stopped, the dressing would then form an antibacterial layer to prevent wound infections and provide an appropriate wound-healing environment.

Further, such dressings are compatible with human skin and possess properties that allow ventilation of the wound and absorption of the wound exudate. Previous studies have also demonstrated the safety of chitosan.

The biocompatibility and biodegradability of chitosan, combined with its haemostatic and anti-infection activity, make it highly useful and advantageous for use in wound dressings. The swine model of femoral artery hemorrhage we used in this study represented a severe injury to the groin area with partial destruction of the femoral artery, causing a life-threatening hemorrhage that is impossible to control with commercial gauze, and not manageable using a tourniquet.

The strength to this study was that the surgical procedures were performed by a researcher who was blinded to group assignment, which increases confidence in the outcome. Although our approach represents a reliable model for examining the efficacy of haemostatic dressings, there are some limitations of this study that should be addressed in future research.

Currently, the biomedical application of most synthetic polymers is limited by insufficient biocompatibility and poor biodegradability. In contrast, natural polymers such as cellulose, chitin, chitosan, and their derivatives have been proven to be biocompatible and biodegradable.

Furthermore, the degradation product of chitosan is nontoxic to humans Chitosan is also useful as a supporting material for tissue engineering. Previous studies have revealed that both chitosan and chitosan oligomers exhibit antibacterial activity, and that chitosan displays greater antibacterial activity than chitosan oligomers 17, Potential future directions should include conducting chitosan-based dressings testing in more challenging animal models, combining chitosan with other materials to achieve stable haemostasis, and modifying the dressings to facilitate handling to further reduce the packing time.

In summary, a large amount of effort has been invested in the investigation of novel haemostatic products. In this study, a swine model of femoral artery hemorrhage was utilized to evaluate the efficacy of CF and CS dressings.

This model mimicked a severe injury to the groin area with partial destruction of the femoral artery, causing a life-threatening hemorrhage that is impossible to control with commercial gauze and not manageable with a tourniquet.

The results revealed that both CF and CS dressings reduced the time to haemostasis and the fluid resuscitation rate relative to commercial gauze, and the CF- and CS-treated animals survived significantly longer than the control animals. Additionally, the two types of chitosan dressing were equally efficacious in mitigating blood loss and promoting survival.

Based on these findings, CF and CS dressings may be suitable first-line treatments for uncontrolled haemorrhage on the battlefield, and require further investigation into their use as alternatives to traditional dressings in pre-hospital emergency care. Home About Chitosan Chitosan Products Pure Ultra-Clean Chitosan — Very High DDA, Low Molecular Weight Low Molecular Weight Low Molecular Weight Chitosan Mushroom Chitosan Low to Medium Molecular Weight Mushroom Chitosan Very High DDA Chitosan Oligosaccharide Mushroom Chitosan Oligosaccharide Crustacean Chitosan Lactate Chitosan Flake Chitin Supply Trimethyl Chitosan Blog Resources Contact.

It is reasonable to postulate that the large blood loss with commercial gauze, and the subsequent high fluid resuscitation rate, reduced the clotting capacity of the blood, leading to unfavorable outcomes. Firstly, considering there are many different types of gauze available for haemostatic management of bleeding, the results in this study can be influenced by the gauze type.

Secondly, we are unable to establish a comprehensive comparison between chitosan-based dressings and gauze because of lack of packing time in this study.

Although chitosan-based dressings significantly reduced time to haemostasis as compared with control, they require more time for packing according to the procedure. Thirdly, this model does not fully mimic battlefield or accident-induced traumatic injuries.

The efficacy of the dressings could be affected by changes in environmental or wound conditions. Lastly, given our small sample size 3 different dressings on 10 animals , this should be followed up with additional studies using a larger sample size.

Download Full Study. Bellamy, R. Causes of death in conventional warfare: implications for combat casualty care research. et al. Trends in trauma deaths at a level 1 trauma center. Injury 48, 5—12 An evidence-based prehospital guideline for external hemorrhage control: American College of Surgeons Committee on Trauma.

Care 18, — Haemorrhage control in severely injured patients. Lancet , — After 18 days, the patient was admitted for the third time, this time with an infected ulcer.

The ulcer was surgically debrided and managed with injections of colistimethate sodium, amoxicillin and potassium clavulanate, and tramadol, as well as oral paracetamol. One day after hospital discharge third admission , the patient was admitted a fourth time with a nonhealing, infected wound.

Another debridement of the wound was performed. The ulcer was infected, with a complex presentation. The patient underwent a thorough evaluation, and acute kidney injury and a nonhealing ulcer were diagnosed. The patient received daily saline dressing changes for 4 weeks. Because wound healing did not improve with the use of standard saline dressings, the authors used chitosan-based dressings to manage the nonhealing ulcer.

Swab culture showed the presence of Pseudomonas aeruginosa , which was sensitive only to colistimethate sodium. Based on the culture report, aztreonam was added to treat P aeruginosa. The chitosan-based dressings were started on the 15 th day of the 4 th admission.

At the time of initial chitosan-based dressing application, the ulcer had been present for 4 weeks and measured 15 cm × 5 cm × 2 cm length, width, and depth, respectively. Pain and exudate levels were reduced, and absence of pseudomonal growth was confirmed by the swab culture.

The authors believe the ease of dressing application and removal was excellent. The patient reported the dressings were comfortable to wear. Because of the improvement in the wound condition, the patient underwent skin grafting and was successfully discharged from the hospital after a total of 58 days during the last admission.

Chronic lower extremity ulcers are common and challenging to heal. Wound healing is a complex process involving the spatial and temporal synchronization of various cell types with distinct roles in the phases of hemostasis, inflammation, growth, reepithelialization, and remodeling.

Despite differences in etiology at the molecular level, various types of chronic wounds share certain common features, including excessive levels of proinflammatory cytokines and proteases, as well as persistent infection and a deficiency of stem cells that also are often dysfunctional.

A moist environment is highly beneficial to wound healing because it increases the rate of epithelization 2-fold. Modern dressings aim to expedite healing, achieve a moist environment, remove excess exudates, provide ongoing protection from or treat bacterial contamination, and reduce odor and pain.

To manage chronic ulcers, the ideal wound dressing should maintain optimum moisture level in the wound bed. The dressing should be nontoxic, act as a bacterial barrier, and be hemostatic for minor bleeding and promote wound healing.

Additionally, it should serve to manage pain and scar formation at the site and should be easily removable. The basic principles of wound care involve thorough assessment along with medical and nutritional optimization, debridement, offloading, and management of ischemia and infection.

Moreover, appropriate preparation of the wound bed is important in providing a proper environment in which tissue repair can occur. Wound characteristics such as edema and odor should also be addressed. One such wound dressing is chitosan based.

Chitosan is polycationic at a pH less than 6, and it readily interacts with negatively charged molecules, such as proteins, anionic polysaccharides, fatty acids, bile acids, and phospholipids. Chitosan-based wound dressings have been successfully used in the management of chronic wounds and ulcers and have been shown to be safe and effective.

In a randomized controlled study evaluating the use of these dressings to manage clinically diagnosed unhealed or nonhealing chronic wounds pressure ulcer, venous leg ulcer, diabetic foot ulcer, and minor infective wound , chitosan-based dressings were associated with a marked reduction in wound size compared with petroleum gauze.

Their study demonstrated that chitosan-based dressings promoted faster wound healing and were easy to remove. Use of the chitosan-based dressing also resulted in an improved healing rate of infected wounds compared with petroleum gauze.

Unlike in the control group, none of the wounds in the treatment group became infected; thus, antibiotics were not required in patients treated with chitosan-based dressings. Clinical study results support the use of chitosan-based gelling fiber dressings on nonhealing, chronic wounds with various complex etiologies.

Furthermore, studies have shown application and removal of the dressings is easy and effective hemostatic outcomes can be achieved. Although the current case had multiple comorbidities in addition to the nonhealing ulcer, the chitosan-based dressing showed remarkable results in managing pain, exudates, and Pseudomonas infection.

The dressings were conformable and exhibited high integrity; they did not disintegrate during removal. The use of chitosan-based dressings resulted in improved wound healing compared with the saline dressings used initially. Complete granulation was achieved after 10 days of treatment with the chitosan-based dressings, whereas saline dressings were used for 4 weeks without any improvement in granulation tissue formation.

The only limitation is that the patient required antibiotics to manage the cellulitis. As a result, it was not possible to evaluate the antibacterial activity of the dressings.

The current case details the effective use of chitosan-based dressings on a complex wound after unsuccessful attempts to achieve healing using conventional methods. The chitosan-based dressings were nonadherent, demonstrated antimicrobial properties, and maintained a moist wound healing environment that is beneficial for wound healing.

In this case, use of the chitosan-based dressings resulted in complete granulation tissue formation within 10 days of application; whereas prior to receiving that dressing, the wound had been unsuccessfully managed with saline dressings for 4 weeks. This case showed early use of chitosan-based dressings may result in improved chronic wound healing outcomes.

Correspondence: Madhukar Kulkarni, MS, R. asterhospital gmail. Frykberg RG, Banks J. Challenges in the treatment of chronic wounds.

Adv Wound Care New Rochelle. Alavi A, Sibbald RG, Phillips TJ, et al. J Am Acad Dermatol. Bhattacharya S, Mishra R.

Pressure ulcers: current understanding and newer modalities of treatment. Indian J Plast Surg. Sullivan T, Barra E.

Diagnosis and management of cellulitis. Clin Med London. Hess CT, Kirsner RS. Orchestrating wound healing: assessing and preparing the wound bed. Adv Skin Wound Care. Pogorielov M, Kalinkevich O, Deineka V, et al.

Haemostatic chitosan coated gauze: in vitro interaction with human blood and in-vivo effectiveness. Biomater Res. Withycombe C, Purdy KJ, Maddocks SE.

Micro-management: curbing chronic wound infection. Mol Oral Microbiol. Ahmed S, Ikram S. Chitosan based scaffolds and their applications in wound healing. Achiev Life Sci. Sood A, Granick MS, Tomaselli NL. Wound dressings and comparative effectiveness data.

Ravichandran P, Chitti SP. Antimicrobial dressing for diabetic foot ulcer colonized with MRSA. Online J Biol Sci. Mo X, Cen J, Gibson E, Wang R, Percival SL. An open multicenter comparative randomized clinical study on chitosan.

Wound Repair Regen. Kordestani S, Shahrezaee M, Tahmasebi MN, Hajimahmodi H, Haji Ghasemali D, Abyaneh MS. A randomised controlled trial on the effectiveness of an advanced wound dressing used in Iran.

J Wound Care. Orig R, Singleton J. A non-comparative evaluation of a chitosan gelling fibre. Br J Nurs. Denyer J, Gibson E. Use of fibre dressings in children with severe epidermolysis bullosa. Rodrigues M, Kosaric N, Bonham CA, Gurtner GC.

Wound healing: a cellular perspective. Physiol Rev. Deutsch CJ, Edwards DM, Myers S. Wound dressings. Br J Hosp Med Lond. Mason S, Clarke C. A multicentred cohort evaluation of a chitosan gelling fibre dressing. Stephen-Haynes J, Toner L, Jeffrey S. Product evaluation of an absorbent, antimicrobial, haemostatic dressing.

Sign in. Podiatry Today. Today's Wound Clinic. Journal Description.

Ideal wound care materials should be flexible, stable, biodegradable, and widely applicable, with the ability to keep wounds moist, stop bleeding, and adsorb exudate Abd El-Hack et al.

With in-depth investigations into the molecular biological mechanisms regarding wound healing and the fast development of tissue engineering biomaterials, a variety of novel biomaterials and hydrogel-like materials have received the most interest attention.

Hydrogel is a 3D structural system formed by the crosslinking of various hydrophilic polymeric chains Lee et al. With both the viscoelasticity of solids and the fluidity of liquids, hydrogels possess similar structural and functional characteristics to extracellular matrices.

The advantages of hydrogels over other typesof wound dressings include: 1 superior hydrophilicity, which enables the hydrogels to adsorb exudate Khorasani et al.

Generally, hydrogels can be classified into native hydrogels and synthetic hydrogels. Native hydrogels are prepared using native polymers including chitosan, sodium alginate, collagen, and sodium hyaluronate as ingredients. Among these, chitosan is one of the most frequently studied and attractive hydrogels.

Many benefits of chitosan and its derivatives on skin wounds have been reported, including: 1 desirable pharmacological actions like antibacterial Mohan et al.

This article reviewed the functions and mechanisms of chitosan as a wound care material to inhibit bacterial infections, stop bleeding, and promote the growth of granulation tissues, along with the applications of chitosan as hydrogels for wound treatment.

The work flow of this article is summarized as Figure 2. Figure 1. Scheme of chitosan chemical structure [cited from literature Abd El-Hack et al. The whole wound healing procedure generally includes four stages which named as hemostasis, inflammation, proliferation, and skin remodeling.

In the hemostasis stage, the coagulation system is activated after blood vessels constrict and platelets aggregate. Fibrinogen is transformed into insoluble fibrin that forms clots to stop hemorrhaging. In the inflammation stage, bacteria and necrotic tissue are cleared by inflammatory cells.

Epithelial cells proliferate and migrate to form epithelial tissue to cover the wound in the proliferation stage. Granulation tissue fills the tissue gap, but epithelialization does not take place. During the final remodeling stage, fresh epidermis and dermis will regenerate to finish the skin repair procedure.

Chitosan and its derivatives will play roles mainly in the first three stages during wound healing. Firstly, they help stop hemorrhaging by promoting the aggregation of platelets and erythrocytes and inhibiting the dissolution of fibrin in the hemostasis stage; Secondly, they can assist to clear bacteria from the wound during the inflammation stage; Finally, they accelerate skin proliferation via promoting the growth of granulation tissue, which is called proliferation stage.

After then, the wound was healed and the skin was remodeled to finish the healing route. Figure 3 illustrates schematically the mechanisms of chitosan-based hydrogels to promote wound healing at the first three stages.

The roles played by chitosan-based materials in these three aspects are discussed in detail as follows. Figure 3. Schematic diagram to illustrate the mechanisms of chitosan-based hydrogels to promote wound healing.

A Platelet plugs composed of platelets, leukocytes, insoluble fibrin, and erythrocytes prevent bleeding at the stage of Hemostasis. Chitosan hydrogel can help to stop hemorrhaging via promoting the aggregation of platelets and erythrocytes and inhibiting the dissolution of fibrin.

Chitosan hydrogel promotes the growth of granulation tissue towards filling the tissue gap. D The final stage, remodeling takes place to finish the whole procedure of skin repair. Chitosan-based hydrogels take effects mainly in the first three stages.

As the first step in wound healing, hemostasis sets the foundation for the subsequent phases. Physiologically, the hemostasis process is composed of four steps.

The coagulation system involves three pathways: extrinsic coagulation, intrinsic coagulation, and common coagulation. The extrinsic coagulation pathway starts with the release of factor III after blood vessels are damaged. The intrinsic coagulation pathway starts with the activation of factor XII caused by the exposure of collagen fibers after blood vessel damage.

Activated factor XII then activates factor XI, which in turn, activates factor IX. The common coagulation pathway utilizes AFX produced in the extrinsic and intrinsic coagulation pathways.

Thrombin is capable of transforming fibrinogen into fibrin, which produces a network to agglomerate erythrocytes, leukocytes, and platelets, creating fibrin clots that contribute to the coagulation process. This step dissolves blood clots to prevent vessel blockage.

However, the superior hemostatic effect of chitosan is not related to the classic coagulation system Leonhardt et al. Chitosan promotes platelet adhesion and aggregation, inducing erythrocyte aggregation and inhibiting fibrinolysis.

Platelet adhesion and aggregation are crucial steps in hemostasis. This process relies upon glycoprotein GP Ia-IIa, GP VI, GP Ib-IX-V, and GP IIb-IIIa present on the platelet membrane, subendothelial collagen, as well as von Willebrand as well as VWF and fibrinogen in plasma factor VWF and fibrinogen in plasma Figure 4A.

When endothelial cells are damaged, the underlying collagen is exposed. Spherical VWF binds to the collagen surface and becomes thread-like under blood flow. The allosteric VWF rapidly binds to GP Ib-IX-V, preventing platelets from flowing away from the wounded site. Platelets are retained by binding to GP VI on the surface of collagen.

The binding of VWF and GP Ib-IX-V activates the relevant signaling pathways in platelets, in turn, activating GP Ia-IIa and GP IIb-IIIa.

Finally, activated GP Ia-IIa and GPIIb-IIIa bind to collagen and VWF, keeping platelets fixed on the collagen surface. The release of ADP and TXA2 from platelets is attributed to the activation of the signaling pathways caused by the binding between VWF and GP Ib-IX-V and between GP VI and collagen.

ADP and TXA2 further activate GPIIb-IIIa on the nearby platelet membranes. The bridging between activated GP IIb-IIIa and fibrinogen results in the aggregation of platelets and thus, the formation of platelet plugs. Chitosan is capable of enhancing GPIIb-IIIa expression on platelet membranes Lord et al.

Moreover, positively charged chitosan can also promote platelet aggregation by interacting with the massive quantity of negatively charged substances on the surface of the activated platelets Wang et al. Figure 4. Hemostatic effect of chitosan on skin wound which occurs at the first stage of wound healing.

A Chitosan enhances the expression of GPIIb-IIIa from platelet. And, positively charged chitosan can interact with negatively charged molecules on the activated platelets, promoting platelet aggregation.

B Erythrocytes aggregate via the interaction between positively charged chitosan and negatively charged molecules on erythrocyte surface. And, chitosan accelerates the formation of fibrin clots by forming a 3D network to capture erythrocytes black arrows point chitosan.

C Chitosan plays a hemostatic role by inhibiting fibrinolysis. The fibrin network agglomerates erythrocytes, leukocytes, and platelets to create fibrin clots.

The surface of erythrocytes is negatively charged due to neuraminic acid residues on their membranes. Fibrin clot formation and erythrocyte aggregation can be promoted by electrostatic interactions between positively charged chitosan and negatively charged groups on the erythrocyte surface Figure 4B Ong et al.

He et al. The study reported a positive correlation between the affinity of chitosan for erythrocytes and the degree of protonation. Moreover, chitosan could capture and agglomerate erythrocytes by forming a 3-D network in blood, thereby promoting fibrin clot formation Wang et al.

During fibrinolysis, fibrin is dissolved by plasmin. Fibrin clots disappear and normal blood flow is restored. However, it desirable to inhibit fibrinolysis, prolonging the existence of fibrin clots, and thus, extending hemostasis.

Chitosan is capable of inhibiting fibrinolysis Figure 4C. Wounded skin undergoes a series of complex repairing processes, including hemostasis, coagulation, inflammation, angiogenesis, granulation tissue development, and re-epithelialization.

The moist and nutrition-rich environment of the wound provides desirable conditions for bacterial growth. Bacterial infections occur when the host immune system fails to clear all invading bacteria.

Therefore, the antibacterial properties of wound dressings need to be seriously considered. Chitosan is widely used in wound treatment due to its superior antibacterial properties Li et al. Currently, the acknowledged possible mechanisms include disrupting bacterial cell walls and cell membranes, chelating trace amounts of metallic cations, interacting with intracellular targets, and depositing on bacteria.

Bacteria can be classified into Gram-negative bacteria and Gram-positive bacteria according to Gram staining results. The cell wall of Gram-negative bacteria is comprised of an outer membrane and a peptidoglycan layer Figure 5A. The outer membrane comprises two asymmetric monolayers.

The inner layer is solely composed of phospholipids, while the outer layer is composed of phospholipids and lipopolysaccharides. The surface of Gram-negative bacteria is negatively charged owing to the phosphate and pyrophosphate groups of lipopolysaccharides in the outer layer.

The cell wall of Gram-positive bacteria is comprised of peptidoglycans and teichoic acids Figure 5B. The surface of Gram-positive bacteria is negatively charged owing to the carboxyl and phosphate groups of teichoic acids. Figure 5. Antibacterial mechanisms of chitosan against Gram-negative A and Gram-positive bacteria B.

a Electrostatic interactions between chitosan and lipopolysaccharides or teichoic -acid disrupt the cell membrane, enabling chitosan to penetrate further into the cell membrane. b Divalent cations are chelated by chitosan, decreasing the stability of the outer membrane.

d High-molecular-weight chitosan deposition on the surface of Gram-negative bacteria hinders bacterial metabolism. The bacterial cell membrane is deformed and ruptured under the unsustainable osmotic pressure, leading to cell content leakage and eventually cell lysis.

Xing et al. aureus for 5 min. The results of SEM observation disclosed that chitosan molecules were adhered to the surface of S. aureus and Escherichia coli E. coli after 30 min of contact, and cell wall disruption and cell content leakage were observed for both bacterial strains.

Apart from the bactericidal activities against both Gram-negative and Gram-positive bacteria, chitosan also exhibits antifungal properties. The antifungal effectiveness of chitosan is positively correlated with the fluidity of the cytoplasmic membrane, which depends upon the amount of PUFAs Verlee et al.

The resistance of fungi to the bactericidal effect of chitosan is divided into chitosan-resistant fungi and chitosan-sensitive fungi. The intrinsic fluidity is very low for fungi with relatively small amounts of PUFAs. The binding between chitosan and negatively charged phospholipids cannot substantially affect the fluidity of the cytoplasmic membrane, and therefore, exhibits little antifungal activity by the inability to alter the permeability of the cytoplasmic membrane.

Fungi that can resist the antifungal activity of chitosan are called chitosan-resistant fungi. Fungi that cannot effectively resist the antifungal activities of chitosan are called chitosan-sensitive fungi.

Divalent cations can stabilize the membrane structure of bacteria. Clifton et al. The results showed that the salt bridges formed by divalent cations and the negatively charged oligosaccharides of lipopolysaccharide are crucial to the structural integrity of the outer cytoplasmic membrane.

The negative charges of the lipopolysaccharide molecules are neutralized by hydrogen bonds and cations, forming networks impermeable to macromolecules and hydrophobic molecules.

Chitosan is a type of chelating agent. Chitosan with a molecular weight of no more than D can penetrate the bacterial cell wall to form complexes with DNA, undermining the function of DNA polymerase and RNA polymerase, and thereby, suppressing the replication and transcription of DNA and RNA [ Figures 5A c ,B c ], which inhibits bacterial proliferation Farhadihosseinabadi et al.

It was found that the brightness of the electrophoretic band diminished with increasing OCNP concentrations. The migration of DNA and RNA from E. Moreover, chitosan with low molecular weight inhibited the protein synthesis of microorganisms [ Figures 5A c ,B c ] Galván Márquez et al.

Galván Márquez et al. cerevisiae using a yeast gene deletion array to explore the chemical-genetic interactions between chitosan and S. The electrostatic interactions between the positively charged amino groups from chitosan and the negatively charged carboxyl groups from proteins were responsible for the inhibition of protein synthesis.

When dissolved in acidic aqueous solutions, chitosan with high molecular weight can form a dense polymeric layer on the bacterial surface that prevents the intake of nutrients or the excretion of metabolites, leading to metabolic disorders and bacterial death [ Figures 5A d ,B d ].

This flocculation effect was verified by SEM observation, showing vesicle-like structures on the outer membrane of chitosan-treated E. coli and Salmonella typhimurium S. typhimurium Helander et al. Tissue regeneration and skin repair start immediately after the skin is wounded.

One of the indispensable stages in skin repair is the formation of granulation tissues composed of inflammatory cells, fibroblasts, and new capillaries. Granulation tissue is capable of refilling the wounded area and promoting epidermal regeneration. Research has shown that chitosan can accelerate skin wound repair by promoting the growth of inflammatory cells represented by macrophages , fibroblasts, and capillaries.

For macrophages, chitosan can promote the secretion of cytokines such as transforming growth factor-β TGF-β , PDGF, and IL TGF-β induces the migration of macrophages to wounded areas, promoting fibroblast proliferation and enhancing collagen secretion.

During skin regeneration, PDGF can enhance angiogenesis and stimulate the migration and proliferation of fibroblasts, and promote the synthesis of glycosaminoglycans, proteoglycans, and collagen, all of which are beneficial to the formation of granulation tissue.

IL-1 is also known to help wound healing by promoting angiogenesis, fibroblast proliferation, and collagen synthesis. Additionally, chitosan can increase the secretion of IL-8 from fibroblasts, which can accelerate the inflammation process and stimulate angiogenesis. The impact of chitosan on fibroblast proliferation depends upon its molecular weight and deacetylation degree.

Chitosan with a high deacetylation degree and low molecular weight has a more pronounced effect to promote fibroblast proliferation Howling et al.

Chitosan is extensively used as a functional material for wound treatment due to its hemostatic effect in the early stages and the ability to inhibit microbial growth and accelerate wound healing.

Chitosan can be utilized in forms such as membranes, hydrogels, fibers, sponges. Hydrogel-like chitosan has received the most attention because of its advantages over other forms of chitosan, including better flexibility, high water content, ability to adsorb exudate, permeability to oxygen, and proper cooling effect that alleviates pain.

Nevertheless, there are certain problems in preparing hydrogels using chitosan alone. For example, chitosan is soluble only in weakly acidic solutions, with relatively weak mechanical strength and deficiencies in certain functions.

To meet the requirements in the field of skin wound repair, modifying techniques such as introducing other chemical components are usually applied. The applications of chitosan hydrogels in skin wound repair are summarized in Table 1. Smart chitosan hydrogels are responsive to external stimuli and have become a focal point of research in the past few years.

Generally, smart chitosan hydrogels are categorized into thermosensitive hydrogels, photosensitive hydrogels, and pH-sensitive hydrogels Shi et al. Thermosensitive hydrogels are widely applied in the biomedical field. This material undergoes a sol-gel transition at body temperature.

The thermosensitive modification of chitosan is achieved by adding substances such as β-glycerophosphate, HPMC, and poloxamer to chitosan hydrogels Blacklow et al. β-glycerophosphate is a common thermosensitive material that can thermally induce the migration of protons from chitosan to glycerophosphate, decreasing electrostatic repulsion and promoting the formation of hydrogen bonds among chitosan chains, causing sol-gel transition.

Nguyen et al. The hydrogel showed good cytocompatibility with both the MC3T3 pre-osteoblast and L fibroblast cell lines. In addition, the hydrogel showed the ability of anti-inflammatory or wound healing M2 macrophage at 14 days after implantation.

Hydroxypropyl methylcellulose possesses the properties of thermal gels. The hydrophilic groups of HPMC molecules form hydrogen bonds with water molecules at low temperatures, creating cage-like structures that enwrap water molecules. As the temperature rises, the hydrogen bonds break, and water molecules are released from the cage-like structures.

The hydrophobic methoxyl groups on the molecular chains of HPMC are exposed and aggregated, eventually forming a 3D network at around 60°C.

At this point, the material is in the form of a gel. Wang et al. To form a gel network at temperatures lower than 60°C, a high concentration of glycerin was added to break the water sheath of the polymer and promote the formation of hydrophobic areas, lowering the phase transition temperature to body temperature.

The results showed that the thermosensitive hydrogel possessed good fluidity, thermosensitivity, low cytotoxicity, and biodegradability, with a pH value of 6. Poloxamer is a triblock copolymer consisting of hydrophilic polyoxyethylene at each end and hydrophobic polyoxypropylene in the middle.

At the critical micelle temperature, poloxamer molecules form spherical micelles with hydrophobic polyoxypropylene as the core and hydrophilic polyoxyethylene as the shell.

As the temperature rises, the accumulation and entanglement of micelles enhance gel formation. For example, by the addition of poloxamer, hUCMSC-exos combined with poloxamer hydrogel existed as a liquid at low temperature and transformed to a semi-solid gel at high temperature, which could fit into the complex and irregular space of diabetic foot wounds.

In addition, poloxamer retained and sustainedly released hUCMSC-exos directly onto the injured tissues, which could attract fibroblasts and endothelial cells to promote wound repair Yang et al. Thermosensitive hydroxybutyl chitosan is a kind of hydrogellic chitosan derivative widely applied in the biomedical and pharmaceutical fields.

No organic crosslinking agent is needed for the sol-gel transition of this biocompatible and reversibly thermo-responsive hydrogel. This hydrogel can be mechanically reinforced by incorporating rod-shaped chitin through adjusting the network structure Sun et al.

pH-sensitive hydrogels are a type of hydrogel whose dimensions vary with ambient pH value. During the wound healing progress, the pH in the wounded area is dynamic. The pH value of normal skin is usually below 5 Lambers et al. Once the skin surface is damaged, the underlying tissue with a pH value of 7.

Chitosan has an approximate pKa of 6. In the acidic environment during the early stage of wound healing, the expansion of chitosan hydrogels can accelerate cell infiltration and proliferation and facilitate oxygen osmosis. Based on pH variation during wound healing, a pH-sensitive chitosan methacrylate hydrogel with adjustable mechanical properties and swelling ratio was designed Zhu and Bratlie, The potential applications of such hydrogel include releasing anti-inflammatory drugs during the initial wound healing phase, which will reduce the extent of inflammation in the inflammation stage and avoid overgrowth in the fibroblast proliferation phase.

Light-responsive smart hydrogels can be produced by incorporating photosensitizers into chitosan hydrogels He et al.

For example, a hybrid hydrogel of carboxymethyl chitosan-sodium alginate containing DVDMS was fabricated Figure 6. The addition of the DVDMS into carboxymethyl chitosan-sodium alginate hydrogel produced photodynamic antimicrobial properties.

Additionally, the hydrogel bulk was helpful for repeatedly photodynamic stimulation, inhibiting bacterial growth while the aFGF content promoted wound healing. Figure 6. Schematic illustration of light-responsive smart carboxymethyl chitosan-sodium alginate hydrogel which is composed of porphyrin photosensitizer DVDMS and PLGA-encapsulated bFGF nanospheres Mai et al.

The Schiff-base bond is a type of dynamic quasi-covalent bond that endows hydrogels with the fluidity of liquids.

A self-adapting hydrogel with viscosity, injectability, and self-healing properties was prepared by a dynamic Schiff base reaction between aldehyde groups from oxidized konjac glucomannan and amino groups from protonated chitosan and tranexamic acid Wang et al.

The hydrogel possessed excellent biocompatibility and antibacterial activity against S. aureus and E. In addition, this hydrogel was capable of filling irregularly shaped wounds and accelerating the healing process.

A self-healing hydrogel was prepared through the Schiff base reaction between the amino groups of carboxymethyl chitosan CMC and the aldehyde groups of rigid rod-like DACNC. The cytotoxicity assay and 3D cell culture demonstrated excellent biocompatibility.

This hydrogel could be injected into irregular and deep burn wounds, then quickly self-heal to reform if broken during injection, and finally, could be painlessly removed by on-demand dissolution using an amino acid solution Figure 7 Huang et al.

This architecture possessed an evenly distributed porous 3D network with a desirable equilibrium between self-healing properties and mechanical strength and, therefore, can be applied to oxygen and nutrient transport in tissue engineering and wound repair Xu et al.

Figure 7. Schematic illustration of a typical example of self-healing hydrogel. A Hydrogel gelation formed from the Schiff base reaction between aminos of CMC and aldehydes of DACNC.

B Dissolution on-demand. After adding amino acid, new Schiff-base linkages were formed from the aldehyde groups of DACNC and amino groups of amino acid, which leaded to removing of the hydrogel painlessly Huang et al. Metallic and metallic oxide nanoparticles such as silver, ZnO, copper, gold, and platinum usually exhibit bactericidal activity.

Thus, the incorporation of these nanoparticles into chitosan hydrogels will enhance the antibacterial properties of the hydrogels Jayaramudu et al.

Among these inorganic antibacterial agents, silver ions and compounds have been the most studied. Silver nanoparticles AgNPs adsorb onto bacterial surfaces via Coulomb attraction forces, penetrate the cell wall, and then bind to intracellular macromolecules like oxidative metabolic enzymes and DNA, leading to structural variation in the bacterial DNA and impeding bacterial metabolism.

Therefore, the incorporation of AgNPs into chitosan hydrogels will enhance their antibacterial properties Kumar et al. Jiang et al. An in vivo tolerance study revealed no skin reactions. Superior antibacterial properties and wound treating ability of the hydrogels were achieved by the sustained release of silver ions.

Kumar et al. A positive correlation between antibacterial efficacy and AgNP concentration was seen Kumar et al. ZnO or ZnO-containing compounds, photocatalytic antibacterial agents, kill bacteria by photoinitiation.

When exposed to light, these materials produce hydroxyl radicals that damage the structural integrity of the bacterial cell membrane, which is detrimental to bacterial proliferation.

Photocatalytic antibacterial materials do not cause secondary pollution and have been widely applied due to their superior bactericidal properties and environmental friendliness.

Khorasani et al. The test results showed that the antibacterial efficacy of the as-prepared hydrogels against S. Copper-based antibacterial materials have drawn research attention not only because of their antibacterial properties comparable to those of silver-based materials, but also their cost-effectiveness.

For example, chitosan-pluronic hydrogels were produced, followed by the incorporation of CuNPs Jayaramudu et al. The hydrogels substantially increased the antibacterial activity against S. coli , with higher antibacterial efficacy at higher CuNP concentrations.

The incorporation of drugs into chitosan-based hydrogels will expand the application scope of the materials, enabling targeted treatments of skin infections, burns, deep wounds, and other skin wounds while the 3D network of the hydrogels can increase the bioavailability of drugs by modulating their release profile.

Microbial infection is the most common factor adversely affecting wound healing, causing swelling, fever, pain, local suppuration, and septicemia. The incorporation of antibiotics into chitosan hydrogels can enhance their efficacy in treating wound infections. For example, mupirocin was added to chitosan-cetyltrimethyl ammonium bromide hydrogels to effectively resist infections caused by S.

aureus and Streptococcus pyogenes S. pyogenes Golmohammadi et al. Skin burns are a common injury with high morbidity and mortality. The increase in reactive oxygen species ROS in cells caused by oxygen and blood deprivation in the early stage of wounds could lead to oxidative stress that is harmful to tissues.

Antioxidants such as vitamins A, D, and E accelerate the healing of burned skin. α-Tocopherol, the hydrolyzate of vitamin E, can protect collagen and glycosaminoglycans from oxidative damage.

Vitamin D is an antioxidant that alleviates tissue inflammation through regulating antigens involved in differentiation, lymphocyte proliferation, innate immune receptor signal transmission, and chemokine expression.

Vitamin A can promote epithelial repair by regulating macrophage functions during the early inflammation stage. Soriano-Ruiz et al. The in vivo tolerance study revealed no skin reactions.

The results of partial-thickness burn wound experiments showed that dermal appendages and similar epidermis, dermis, and stratum corneum appeared in animal skins treated with the hydrogel loaded with antioxidant molecules vitamin A, D, and E.

Promoting wound healing for deeply burned skin remains a major challenge. Hesperidin has been reported to possess the capability of repairing deep wounds through inducing VEGF gene expression and stimulating the growth of epithelial cells and collagen deposition Haddadi et al.

It was loaded into alginate-chitosan hydrogels with various concentrations to enhance deep wound healing. The in vivo tests verified that wound closure was accelerated compared to treatment with bandages Bagher et al. The modification of hydrogels with cells and bioactive molecules like growth factors has drawn attention due to its ability to accelerate wound healing by inducing intracellular signaling and stimulating the synthesis of skin repair-related proteins Guo et al.

Adipose-derived stem cells ASCs can secrete several types of angiogenic growth factors that promote angiogenesis in wounded tissue Guilak et al. Cheng et al. In vitro tests showed that a higher concentration of VEGF was present in the supernatant of the hydrogel.

This hydrogel can be used for therapeutic angiogenesis. BMSCs have been shown to be a candidate for cell therapy for keloids, a kind of benign fibroproliferative tumor in which dermal and subcutaneous extracellular matrices excessively accumulate and outgrow the original wounded area Fang et al.

A keloid is not only unaesthetic but also prone to becoming cancerous. A previous study reported that Arg-Gly-Asp-grafted hydroxybutyl chitosan hydrogel combined with BMSCs inhibited extracellular matrix synthesis via paracrine signaling, and thus, is a promising candidate for subcutaneous injection treatment for keloids Qu et al.

A variety of cytokines participate in repair after skin injury. The biocompatibility and biodegradability of chitosan, combined with its haemostatic and anti-infection activity, make it highly useful and advantageous for use in wound dressings.

The swine model of femoral artery hemorrhage we used in this study represented a severe injury to the groin area with partial destruction of the femoral artery, causing a life-threatening hemorrhage that is impossible to control with commercial gauze, and not manageable using a tourniquet.

The strength to this study was that the surgical procedures were performed by a researcher who was blinded to group assignment, which increases confidence in the outcome.

Although our approach represents a reliable model for examining the efficacy of haemostatic dressings, there are some limitations of this study that should be addressed in future research. Currently, the biomedical application of most synthetic polymers is limited by insufficient biocompatibility and poor biodegradability.

In contrast, natural polymers such as cellulose, chitin, chitosan, and their derivatives have been proven to be biocompatible and biodegradable. Furthermore, the degradation product of chitosan is nontoxic to humans Chitosan is also useful as a supporting material for tissue engineering.

Previous studies have revealed that both chitosan and chitosan oligomers exhibit antibacterial activity, and that chitosan displays greater antibacterial activity than chitosan oligomers 17, Potential future directions should include conducting chitosan-based dressings testing in more challenging animal models, combining chitosan with other materials to achieve stable haemostasis, and modifying the dressings to facilitate handling to further reduce the packing time.

In summary, a large amount of effort has been invested in the investigation of novel haemostatic products. In this study, a swine model of femoral artery hemorrhage was utilized to evaluate the efficacy of CF and CS dressings.

This model mimicked a severe injury to the groin area with partial destruction of the femoral artery, causing a life-threatening hemorrhage that is impossible to control with commercial gauze and not manageable with a tourniquet.

The results revealed that both CF and CS dressings reduced the time to haemostasis and the fluid resuscitation rate relative to commercial gauze, and the CF- and CS-treated animals survived significantly longer than the control animals. Additionally, the two types of chitosan dressing were equally efficacious in mitigating blood loss and promoting survival.

Based on these findings, CF and CS dressings may be suitable first-line treatments for uncontrolled haemorrhage on the battlefield, and require further investigation into their use as alternatives to traditional dressings in pre-hospital emergency care. Home About Chitosan Chitosan Products Pure Ultra-Clean Chitosan — Very High DDA, Low Molecular Weight Low Molecular Weight Low Molecular Weight Chitosan Mushroom Chitosan Low to Medium Molecular Weight Mushroom Chitosan Very High DDA Chitosan Oligosaccharide Mushroom Chitosan Oligosaccharide Crustacean Chitosan Lactate Chitosan Flake Chitin Supply Trimethyl Chitosan Blog Resources Contact.

It is reasonable to postulate that the large blood loss with commercial gauze, and the subsequent high fluid resuscitation rate, reduced the clotting capacity of the blood, leading to unfavorable outcomes.

Firstly, considering there are many different types of gauze available for haemostatic management of bleeding, the results in this study can be influenced by the gauze type.

Secondly, we are unable to establish a comprehensive comparison between chitosan-based dressings and gauze because of lack of packing time in this study. Although chitosan-based dressings significantly reduced time to haemostasis as compared with control, they require more time for packing according to the procedure.

Thirdly, this model does not fully mimic battlefield or accident-induced traumatic injuries. The efficacy of the dressings could be affected by changes in environmental or wound conditions. Lastly, given our small sample size 3 different dressings on 10 animals , this should be followed up with additional studies using a larger sample size.

Download Full Study. Bellamy, R. Causes of death in conventional warfare: implications for combat casualty care research. et al. Trends in trauma deaths at a level 1 trauma center. Injury 48, 5—12 An evidence-based prehospital guideline for external hemorrhage control: American College of Surgeons Committee on Trauma.

Care 18, — Haemorrhage control in severely injured patients. Lancet , — Te acute coagulopathy of trauma: mechanisms and tools for risk stratifcation. Shock 38, — Acute coagulopathy of trauma: hypoperfusion induces systemic anticoagulation and hyperfbrinolysis.

J Trauma 64, — Impact of hemorrhage on trauma outcome: an overview of epidemiology, clinical presentations, and therapeutic considerations. J Trauma 60, S3—11 Injury severity and causes of death from operation iraqi freedom and operation enduring freedom: — versus J Trauma 64, S21—27 Epidemiology of trauma deaths: a reassessment.

J Trauma 38, — Prehospital control of life-threatening truncal and junctional haemorrhage is the ultimate challenge in optimizing trauma care; a review of treatment options and their applicability in the civilian trauma setting.

Scand J of Trauma, Resusc Emerg Med 24, J Trauma 66 , — The Strategies of Natural Polysaccharide in Wound Healing, Wound Healing — Current Perspectives, K.

Stricker-Krongrad, A. Efficacy of chitosan-based dressing for control of bleeding in excisional wounds. ePlasty 18 , — The modulation of platelet adhesion and activation by chitosan through plasma and extracellular matrix proteins. Biomaterials 32 , — Functionalized chitosan and its use in pharmaceutical, biomedical, and biotechnological research.

Chem, Eng. Antibacterial activity of chitosans and chitosan oligomers with different molecular weights. Food Microbiol. Antibacterial activity of chitosans with different degrees of deacetylation and viscosities.

Food Sci. Yao-Horng Wang, et al. This article is a copy of the published paper with very minor adjustments in its wordings and format. The purpose of this article, blog, or study is for information purposes only in the spirit of getting information to persons with an interest s on its topic.

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