Mechanically strong and needs-based soluble chitosan hydrogels for wound dressings (2023)

carbohydrate polymers

294 bind,

15. October 2022

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Physical hydrogels fromrenChitosan retains the natural properties of chitosan making it an ideal candidate for wound dressing applications, however its low mechanical strength severely limits its use. In addition, chitosan dressings tend to stick to wounds, making replacement difficult. Here, physical hydrogels were produced from pure chitosan by first dissolving chitosan in an alkaline aqueous solution and then thermally dissolving itgelationand solvent change. The gels showed better mechanical properties than the previously prepared gels. They were soluble in dilute acetic acid and thus soluble when needed. When used as a wound dressing and changed during mechanical debridement, the gels achieved faster wound closure than gauze. Even faster wound closure was achieved when modified by dissolving them with acetic acid solution. In addition to faster healing, the dissolvable-on-demand dressing can also reduce scarring and restore normal skin anatomy and function.


Chitosan, the only cationic naturally occurring polysaccharide, has found numerous biomedical applications (Dash et al., 2011). In particular, its unique properties such as biocompatibility, non-toxicity, biodegradability, non-antigenicity, antimicrobial activity and hemostatic ability make it a great potential for wound care (Bano et al., 2017; Hu & Xu, 2020; Peng et al., 2022). A large number of chitosan-based wound dressings have been reported to date. These dressings can accelerate closure, neovascularization, and permanent regeneration of the dermis in wounds (Bano et al., 2017). Hydrogel dressings are known to provide a moist healing environment that promotes granulation, epithelialization, and autolytic debridement (Ghobril & Grinstaff, 2015; Lima & Passos, 2021). Many chitosan-based hydrogels have been developed in recent years, including chemically crosslinked (Huang et al., 2013; Ono et al., 2000) and physically crosslinked (Cao et al., 2021; Li et al., 2017; Ong et al ., 2008) was developed for wound care.

To synthesize chitosan-based hydrogels, the structure of chitosan was usually modified to make it water soluble and/or crosslinked (Cao et al., 2021; Huang et al., 2013; Ishihara et al., 2002; Ong et al ., 2008; Ono et al., 2000). Usually other polymers were added (Ding et al., 2021; Gomes Neto et al., 2019; Hu et al., 2018; Huang et al., 2013; Huang et al., 2019; Madhusudana Rao et al., 2017, Madhusudana Rao et al., 2018; Rao et al., 2016). Although these efforts may improve certain properties of the hydrogels, chitosan's unique properties, such as As antibacterial and biodegradable properties are impaired. In this context, pure chitosan physical hydrogels are extremely attractive because the natural biological and physico-chemical properties of chitosan, e.g. B. biodegradability, antimicrobial activity and hemostatic ability, which are essential for application in wound care, could be retained. Pure chitosan physical hydrogels are typically prepared by first dissolving chitosan in dilute acids and then neutralizing it with a base, such as ammonia gas (Li et al., 2017; Montembault et al., 2005; Ribeiro et al., 2009). Like many other physical hydrogels, chitosan physical hydrogels usually have poor mechanical properties (Li et al., 2017). Because the primary purpose of a wound dressing is to act as a physical barrier to protect the wound from the environment, an ideal wound dressing should be flexible, durable and resistant to stress (Peh et al., 2000). The poor mechanical properties of physical hydrogels severely limit their use in wound care. However, few studies in this direction have been published. In order to improve the mechanical properties of the chitosan hydrogel wound dressing (Boucard et al. (2007), they previously synthesized a physical hydrogel with a two-layer structure consisting of a rigid protective layer with good mechanical properties and a soft and flexible layer to interact with dem wound Recently, Li Li et al (2017) synthesized a chitogel by ammonia-induced gelation of chitosan in the presence of AgNO3. Both the mechanical and antibacterial properties were improved compared to the gel made without AgNO3.

Another major problem with wound dressings is that they stick to wounds and need to be replaced at regular intervals. Currently available dressings are usually replaced by surgical or mechanical debridement, which is painful, causes injury to the newly formed tissue, and delays the healing process (Konieczynska et al., 2016; Lu et al., 2018). Strategies that allow for gentle, less invasive, and easy dressing changes are highly desirable. Such strategies will avoid sequelae and alleviate the suffering of patients. Many on-demand dissolvable dressings have been developed in recent years (Ding et al., 2021; Hua et al., 2019; Konieczynska et al., 2016; Lu et al., 2018; Lu et al., 2020; Xu et al et al., 2017; Zhao et al., 2020). These dressings can dissolve in a liquid, allowing for easy, non-invasive dressing changes. Chitosan hydrogel dressings also adhere to wounds and are difficult to change (Ono et al., 2000). The development of on-demand soluble chitosan hydrogels should be a possible way to solve this problem (Ding et al., 2021; Ono et al., 2000).

Here we reported on a physical hydrogel made from pure chitosan with improved mechanical properties and its application as an on-demand dissolvable wound dressing. In contrast to the traditional approach, an aqueous alkali-urea solution, a solvent previously developed to dissolve cellulose (Cai & Zhang, 2005), was used to dissolve chitosan at low temperature instead of its usual solvent, dilute acids (Duan et al . , 2015; Li et al., 2014; Li et al., 2015). The resulting solutions gelled upon heating (Li et al., 2014; Shi et al., 2020). After removing alkali and urea by changing the solvent, pure chitosan physical hydrogels were obtained (Li et al., 2014). The resulting chitosans are mechanically strong. In addition, they can be dissolved in diluted acetic acid, so they can be used as a dissolvable wound dressing when needed. Using a full skin injury model in rats, it was shown that this new wound dressing accelerates wound healing. In addition, scarring was reduced. Both effects could be attributed to the non-invasive dressing change, which avoids undesirable secondary damage to the wounds.

section excerpt


Chitosan with a degree of deacetylation of 85% and an average molecular weight was obtained from Sigma-Aldrich. The viscosity average molecular weight was determined to be 299 kDa. NaOH and urea were purchased from Tianjin Chemical Reagent Company (Tianjin, China). Reagents were of analytical grade and used without further purification.

Production of chitosan hydrogels

The chitosan hydrogels were prepared using the alkali method according to Li et al. manufactured. (2014). First, the alkaline solvent was prepared by dissolving 7 g NaOH and 12 g

Hydrogel Preparation

In contrast to the previous method, in which pure chitosan physical hydrogels were prepared by first dissolving chitosan in acidic solutions and then precipitating with an alkaline solution or alkaline gas (hereinafter referred to as the acid method) (Li et al., 2017) , these are chitosan hydrogels, were prepared by first dissolving chitosan in an aqueous NaOH/urea solution (Li et al., 2014), followed by thermogelling the solution and removing NaOH and urea by solvent switching ( hereinafter referred to as the alkaline method) (Li


In summary, a mechanically strong and, if necessary, soluble physical hydrogel made of pure chitosan for the wound dressing was developed. Unlike the conventional method in which chitosan is first dissolved in an acidic solution and then gelled with a base, here chitosan was first dissolved in an alkaline aqueous solution and gelled by heating and changing the solvent. The mechanical properties of gels obtained with the alkaline method are much better than those obtained with the acid method, which makes it possible

author contribution

All authors analyzed the results for the design and implementation of the research.

(Video) Hydrogels and their therapeutic application - by Claire Cai

CRediT Author Statement

Ying Luo:Conceptualization, methodology, data curation, writing - original draft.Hun Cui:Data curationLei Zou:Data curationYiping Zhao:Supervision, Projektadministration.Li Chen:Conceptualization, Supervision, Project Management, Writing - Reviewing and Editing.Ying Guan:Supervision, Projektadministration.Yongjun Zhang:Conceptualization, methodology, supervision, project management, writing - review and editing.

Declaration of Competing Interests

The authors declare that they are not aware of any competing financial interests or personal relationships that might appear to have influenced the work described in this article.


We are grateful for the financial support of this workNational Natural Science Foundation in China(grant no.:51625302,51873091,52033004And52073146) AndTGUFiber Studies Grant.


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    How is chitosan used for wound healing? ›

    Chitosan accelerates the wound healing process by stimulating inflammatory cells, macrophages, and fibroblasts, hence boosting the inflammatory phase. In this way, the inflammatory phase is reduced, and the proliferative phase starts sooner in the wound healing process [128].

    What is chitosan-based film for wound healing? ›

    Chitosan polymer is known to have wound healing properties and has been used as a treatment due to its intrinsic antimicrobial properties and its ability to deliver other agents to wounds and burns [23].

    What is the chitosan dressing? ›

    Chitosan-based dressings are a novel dressing in wound care with the ability to accelerate clotting time. Used on full-thickness wounds, chitosan dressing provides a safe and efficient method for hemostasis in excisional wounds in an animal model utilizing heparin anticoagulation.

    What is hydrogel wound dressing made of? ›

    Hydrogel dressings are composed of about 90% water suspended in a gel made up of insoluble hydrophilic polymers which swell up on contact with water. They are typically made from polymers of synthetic molecules, such as polymethacrylate and polyvinylpyrrolidine, and some are combined with alginate dressings.

    What is the disadvantage of chitosan hydrogel? ›

    Meanwhile, weak mechanical properties of chitosan hydrogels are also a major drawback for tissue engineering scaffold. In addition, they show a mismatching degradation rate, show low cell adhesion, and lack pro-therapeutic effects in vascular regeneration [123].

    What are the advantages and disadvantages of chitosan? ›

    The advantages of chemical production of chitosan include the short processing time and the applicability of this methodology at the industrial scale. However, some disadvantages are found: This method is environmentally unfriendly, due to the large amount of alkaline waste and organic material.

    What are the advantages of chitosan hydrogel? ›

    Chitosan-based hydrogels are considered as ideal materials for enhancing wound healing owing to their biodegradable, biocompatible, non-toxic, antimicrobial, biologically adhesive, biological activity and hemostatic effects.

    Does chitosan have antibacterial activity? ›

    The most prevalent proposed antibacterial activity of chitosan is by binding to the negatively charged bacterial cell wall causing disruption of the cell, thus altering the membrane permeability, followed by attachment to DNA causing inhibition of DNA replication and subsequently cell death (Nagy et al. 2011).

    What are the benefits of chitosan in skin care? ›

    Chitosan has antimicrobial properties, keeping the skin protected against harmful microorganisms that cause inflammation, infection, acne and other skin conditions. Chitosan also effectively removes excess sebum, preventing from further inflammation and infection while keeping skin soft, smooth and glowing.

    When should you not use hydrogel? ›

    Contraindications. There are two types of wounds for which a hydrogel dressing is not advised — full-thickness burns and moderate- to high-exuding wounds.

    What are the side effects of chitosan? ›

    Side effects of chitosan supplements may include constipation, nausea, and an upset stomach ( 11 , 12 ). If you're allergic to shellfish or mushrooms, you should avoid chitosan supplements.

    How does hydrogel heal wounds? ›

    Hydrogel Dressings

    They provide a moist environment in the wound site which promotes tissue regeneration by granulation and re-epithelialization [41,42]. Hydrogel dressings have been conveniently used for the treatment of chronic wounds.

    How long can hydrogel dressing stay on? ›

    Dressings such as Granuflex ™, Comfeel ™, and Tegasorb ™ are available as sheets or thin films [25]. Hydrocolloids are prescribed for full-size and partial wounds with low to medium exudation, wounds with scab formation and that can remain on the wound surface for up to seven days [26].

    What type of wound requires a hydrogel dressing? ›

    Wounds that have little to no excess fluid, like second degree or higher burns, require hydrogel dressings. This dressing allows moisture to stay at the surface of the wound, allowing for a natural environment for cleaning the wood and for the body to rid itself of dead tissue.

    What are the side effects of hydrogel dressing? ›

    Nevertheless, side effects such as redness, edema, bruising, pain, pruritus, and heat sensation have been reported.

    Is chitosan FDA approved? ›

    Regulatory Status: As a pharmaceutical excipient, chitosan has no regulatory status and may not be sold for use in food or approved drugs unless it can be qualified through FDA approval mechanisms for food components or finished new drug dosage forms.

    What is the weakness of chitosan? ›

    Chitosan has antibacterial and antifungal properties which qualify it for food protection, however, its weak mechanical properties, gas and water vapor permeability limit its uses.

    Who should not take chitosan? ›

    If you are allergic to shellfish, you should not take chitosan. Chitosan may interfere with how blood thinners work in your body. If you take warfarin, talk to your doctor before taking this supplement. It also might interfere with the way some antiviral agents work.

    What are the precautions of chitosan? ›

    and Warnings

    It might cause stomach upset, constipation, or gas. When applied to the skin: Chitosan is possibly safe when used short-term. Pregnancy and breast-feeding: There isn't enough reliable information to know if chitosan is safe to use when pregnant or breast-feeding. Stay on the safe side and avoid use.

    Is chitosan inflammatory? ›

    When macrophages are polarized towards an M1 state, chitosan enhances the release of pro-inflammatory cytokines. In macrophages polarized towards an M2 state, chitosan enhances the release of anti-inflammatory cytokines.

    Does chitosan raise blood pressure? ›

    This meta-analysis indicates that chitosan consumption significantly decreases DBP at higher dosage and in shorter-term interventions, while chitosan has no significant effects on SBP.

    Is chitosan safe for skin? ›

    Chitosan is a natural antioxidant , exhibiting antioxidant activity that can be greatly beneficial to human health. Antioxidants play a key role in maintaining a healthy body and chitosan's antioxidant properties make it excellently suited for skincare products.

    What are the disadvantages of chitosan polymer? ›

    A major disadvantage that limits the widespread application of chitosan in a living system is that it is not soluble in aqueous solutions. This is due to extra-molecular hydrogen bonds forming a rigid crystal structure. However, it dissolves in acid solutions at a pH not greater than 6.

    What is the swelling ratio of chitosan hydrogel? ›

    Under similar conditions, Rohindra et al. reported a swelling ratio of 6.02 for hydrogel films [52] . The slight increase may be due to the presence of PEO, which has been reported to increase the swelling ratio of chitosan and CS/PEO hydrogels [53]. ...

    Is chitosan an antifungal? ›

    Chitosan has a great potential as antifungal agent to treat diseases caused by human pathogenic fungi [32,33,34,35,36]. Sensitive fungi show energy-dependent plasma membrane permeabilisation by chitosan [37]. This polymer also displays antibiotic activity against pathogenic bacteria [23,38,39,40,41].

    What is the antimicrobial activity of chitosan hydrogel? ›

    The antibacterial activity of chitosan is attributed to its polycationic structure, which exerts a strong electrostatic interaction with the negatively charged bacterial cell surface, disturbing the cell membrane and inducing leakage (10).

    What is the anticancer property of chitosan? ›

    Both chitosan and its various derivatives have been reported to selectively permeate through the cancer cell membranes and show anticancer activity through the cellular enzymatic, antiangiogenic, immunoenhancing, antioxidant defense mechanism, and apoptotic pathways.

    How does chitosan affect the skin? ›

    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-1.

    What are the effects of chitin and chitosan on collagen synthesis in wound healing? ›

    Chitin and chitosan have a beneficial influence on the various phases of wound healing, such as fibroplasia, collagen synthesis and contraction, resulting in faster healing.

    What is chitosan widely used for? ›

    Chitosan possesses antibacterial and antifungal properties and has been extensively studied as a potential natural antimicrobial agent in the pharmaceutical, cosmetic, agricultural, and food industries. The antimicrobial properties of chitosan are affected by molecular weight, degree of acetylation, and pH.

    Can bacteria grow on hydrogel? ›

    The presence of nutrients within a hydrogel facilitates bacterial growth and proliferation due to nutrient consumption. For instance, a study evaluated the influence of different bacterial nutrient media encapsulated within 1% agarose hydrogels on bacterial growth.

    What precautions should be taken when using hydrogel dressing? ›

    Precautions: External use only. Keep out of reach of children. Avoid contact with eyes. In case of accidental ingestion, seek professional help.

    Is hydrogel a debriding agent? ›

    Hydrogels are widely used as debriding agents in the managementof a variety of wounds. These products also help to maintain a moist wound environment recognised as being beneficial in wound healing.

    Does chitosan clot blood? ›

    Finally, chitosan can stop a hemorrhage due to the interactions with negatively charged thrombocytes and erythrocytes resulting in blood clot formation [32,33]. Thus, it constitutes a great candidate for the most efficient hemostatic agent with various bioactive properties.

    Does chitosan affect kidneys? ›

    Chitosan is the name of a group of similar naturally-occurring molecules. There is some very preliminary evidence that chitosan's presence in your kidneys may provide benefits to these internal organs — especially for people with polycystic kidney disease.

    How much does chitosan cost? ›

    Prices for chitin and chitosan range from $10 to $1,000 per kilogram depending on product quality.

    Is hydrogel good for deep wounds? ›

    When used as a wound dressing, hydrogel not only forms a physical barrier and removes excess exudate but also provides a moisture environment that promotes the wound healing process. Additionally, hydrogel can perfectly fill irregularly shaped wounds and deal with deep bleeding efficiently.

    Can you put hydrogel on open wound? ›

    Hydrogel dressings are one the most widely used methods of dressing a wound. Made of roughly 90% water, hydrogels provide adequete moisture which can accelerate healing time. Initially, they were designed to help in regulating fluid exchanges on the surface of the wound.

    What is the best dressing to remove Slough? ›

    There are dressings specifically designed to promote autolytic debridement, which include thin films, honey, alginates, hydrocolloids, and PMDs. Hydrogels and hydrocolloids are additional dressing choices that may be effective in removing slough.

    Can you leave a dressing on too long? ›

    The original dressing can be left in place for up to two days (or as advised by the nurse/doctor), as long as it is not oozing. The wound must be kept dry for two days. If the dressing becomes wet from blood or any other liquid, it must be changed.

    Should you keep a wound moist or dry? ›

    Gently wash the area with mild soap and water to keep out germs and remove debris. To help the injured skin heal, use petroleum jelly to keep the wound moist. Petroleum jelly prevents the wound from drying out and forming a scab; wounds with scabs take longer to heal.

    When should you stop dressing a wound? ›

    Once the wound has formed a scab, there is no longer the need to cover it with a bandage as the scab now acts as a protective barrier. Keep the area clean, but be gentle so that you do not accidentally remove the scab.

    What does chitosan do for skin? ›

    Chitosan has antibacterial, antioxidant, and immunomodulatory effects that can prevent the infection of wounds and promote healing through soft tissue regeneration, making it a natural wound-dressing material.

    How does chitosan work as an antimicrobial? ›

    The most prevalent proposed antibacterial activity of chitosan is by binding to the negatively charged bacterial cell wall causing disruption of the cell, thus altering the membrane permeability, followed by attachment to DNA causing inhibition of DNA replication and subsequently cell death (Nagy et al. 2011).

    How do you use chitosan? ›

    Dosing. Chitosan has most often been used by adults in doses of 1-1.35 grams by mouth daily for up to 12 weeks. It's also used in mouthwashes, gels, chewing gum, eye drops, and wound dressings. Speak with a healthcare provider to find out what type of product and dose might be best for a specific condition.


    1. Making a highly swellable hydrogel | Swelling and Temperature Sensitivities effect Comonomer Content
    (Polymer Scope)
    2. Multifunctional Hydrogels for Sustainable Energy and Environment
    (Advanced Materials Congress Lectures)
    3. Hydrogels - Part 1
    4. Insulin Stimulated Mesenchymal Stem Cells in Wound Healing - Ronke Olabisi
    (UCI Media)
    5. Terasaki Talk: Advances in Shear-Thinning Hydrogels for Biofabrication and Tissue Repair
    (Terasaki Institute)
    6. Insulin-Stimulated Mesenchymal Stem Cells in Wound Healing
    (UCI Sue and Bill Gross Stem Cell Research Center)


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