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Research Progress on Chitosan and Its Derivatives in Promoting Wound Healing


The skin is the largest organ of the human body and it is a very important shield for human skin. It can stop the outside world from scratching the skin. Even if the skin is capable of self-repair, when the external environment leads to a wide range of skin lesions, the skin heals slower or doesn't repair itself. You have to undergo skin transplantation for the appropriate healing result. Wund repair is intricate and programmed, and broken down into inflammation, proliferation and remodeling. These are the three steps, which are like three steps in the process, but all three steps of the healing process overlap. Skin repair is very dependent on the wound size. Most of the time, when bigger defects appear in skin, they require longer to grow and mature and to fill, a biomolecular cascade of processes. It is the multiple determinants of wound healing – the hyperactive phagocytosis of macrophages during inflammation, platelet-derived growth factor and fibroblast growth factor in blood – that can drive wound healing, so the pathology of trauma is the wound healing process. Wound healing can be slow because of a variety factor including but not limited to: 1. Tissue ischemia; 2. Foreign objects in the infection; 3. Infection; 4. Systemic diseases. These will cause malfunctions in the response process of all wound healing processes, leaving unsettled scars. A dry, clean setting can speed wound healing and decrease inflammation. The ideal wound dressing is very diverse, it should be humidity, drain the wound exudate, heat insulation, gas-exchange, wound near the wound, and antibacterial. The more people insist on the aesthetic of wound care, the more the purpose of conventional dressings may be too suitable, and so new synthetic dressings have replaced what traditional dressings lack.

Stages of wound healing and various properties of multifunctional hydrogel wound dressings used in wound healing (Guo W, et al.; 2024)Figure 1. Stages of wound healing and various properties of multifunctional hydrogel wound dressings for wound healing. (Guo W, et al.; 2024)

Overview of Chitosan

Chitosan is a natural cationic polysaccharide, a product of partial complete deacetylation of chitin, and a derivative of chitin. Chitosan comes from many places, such as the shells of crustaceans, the cell walls of fungi and algae, the exoskeletons of insects, and the rhizomes of mollusks. Therefore, the sources of chitosan are very wide and the resources are abundant. Chitosan also has biocompatibility and biodegradability, low toxicity, antibacterial properties, and antioxidant properties. Chitosan can be processed into products such as fibers, porous scaffolds, and gels. Due to its good biocompatibility, non-toxicity, and biodegradability, it has the advantages of anti-cancer, antibacterial, and certain immune effects on external stimuli in medical treatment. These advantages can be used to promote wound healing. Chitosan and its derivatives also have stronger antibacterial and antioxidant effects, so they can be used as one of the raw materials widely used in the medical field. At present, the main applications of chitosan in biomedicine are: chitosan-based nanomaterials for the treatment of burn wounds, and combining chitosan derivatives with calcium alginate to make medical dressings. Because chitosan has many of the above valuable properties, it is also widely used in medicine, food processing and agriculture, cosmetics production and waste disposal.

New Synthetic Dressing

New synthetic dressings are indispensable medical products for promoting wound healing in modern times. The rapid growth of the new synthetic dressing market has brought many market opportunities. Due to the development of modern materials science and industry, clinical medical dressings have also made epoch-making progress. The birth of a variety of new synthetic dressings plays a very important role in clinical wound healing. In the research and discussion of favorable factors for wound healing, it was found that a moist environment has an important impact on wound healing. Since dry dressings lack this advantage, traditional dry dressings have been transforming into new synthetic dressings. New synthetic dressings have more obvious advantages than traditional dressings. An ideal medical dressing should have significant advantages in terms of cost, resources, appearance, storage method, and skin sensitization. Traditional dry dressings can only provide physical protection and have limitations in wound healing and infection prevention. The secondary separation of dry dressings can cause secondary damage to the skin. New synthetic dressings have more advantages than traditional dressings: 1. Water barrier; 2. Isolate microorganisms and protect the wound surface; 3. Exchange gas with the outside world; 4. Absorb excess secretions from the wound; 5. Maintain appropriate moisture on the wound surface.

  • Liquid form Based on Chitosan

This liquid dressing consists of acrylate copolymer and its main function is to act as a physical barrier over the wound area and keeps the wound moist. As per the properties of chitosan paper, it is antibacterial and anti-allergenic. The dressing form is very easy to use and non-irritating. It is a liquid before squirting. It only takes a few minutes to dry film and form on the surface of the wound and around the wound. Liquid dressings' benefits were summarised using 9 randomised controlled trials: 1. It's very easy to see the surface of the injury; 2. Reduce wound allergies; 3. Reduce patient pain; 4. Improve patient comfort. It can be combined with the properties of chitosan and can not only help heal a wound in a moist situation, it will also act as an anti-inflammatory and prevent scar hyperplasia.

  • Hydrogel form Based on Chitosan

Hydrogel is composed of polymer materials, and its structure contains many hydrophilic groups, so it can absorb dozens or even hundreds of times its own weight of water. Because hydrogel has a high-water content, the wound can be cooled by it, reducing the temperature sensation associated with inflammatory tissue. Hydrogels also have good cell adhesion, can directly contact wounds, reduce fluid loss, prevent secondary infection damage, and can be used topically to help wounds heal. The polymer hydrogels combined with chitosan are very popular in the field of medical dressings because of their good biocompatibility, resource processing, and controllability of mechanical properties.

  • Chitosan-based Hydrocolloid Form

The main components of hydrocolloids are: 1. Sodium carboxymethyl cellulose; 2. Gelatin; 3. Pectin; 4. Adhesive. Hydrogel is an adsorbent and semi-permeable dressing. The benefit is that it takes up a small or moderate amount of wound exudate and keeps the wound moist during healing. Compared with hydrogel dressings, its restrictions are more obvious. The use of hydrocolloid dressings is extremely important in terms of selectivity. If used on dry wounds, it may adhere to the wound completely and be difficult to remove, causing skin damage. If used on highly exudated wounds, it will cause complete immersion around the wound.

  • Chitosan-based Sponge Form

Related research results show that the physical and chemical properties of sponge-shaped dressings are significantly different from those of other forms of dressings. Its main characteristics include: 1. Water absorption; 2. Water retention; 3. Porosity. Sponge-shaped dressings combined with chitosan can clearly show the hemostatic and good biocompatibility characteristics of chitosan. Related research results show that a hemostatic sponge with microchannels is made by combining chitosan derivatives quaternized chitosan and carboxylated cellulose. The sponge combined with chitosan has the characteristics of low density and high porosity, and has obvious therapeutic effects in liquid absorption tests and in vitro hemostasis experiments. The characteristics of the dressing are summarized through experiments: 1. Smooth surface; 2. Uniform pore size and number; 3. Considerable flexibility; 4. Strong ability to promote wound healing.

Application of Chitosan Derivatives in Wound Healing

Chitosan is a deacetylated form of chitin. It is plentiful in nature and resourceful. But chitosan is insoluble in water and almost all solvents, so it's not very popular in many industries. Various functional groups of the chitosan structure can also be extracted from the material with more derivatives in chemical modification. -OH and -NH2 in chitosan molecules are powerful and can be synthesized into derivatives with improved physical and chemical attributes. Its physical and chemical properties can be improved by chemical alteration, or even the physical and chemical properties of chitosan themselves. With this sort of modification, chitosan is ready to enter many medicine applications. It is the derivatives of modified chitosan which are biocompatible, degradable, non-toxic, antibacterial and hemostatic. Hemostaticity is obtained by changing it to activate the platelets and the complement system and increase the collection of red blood cells, but this is not obtained from chitosan but from chitosan derivatives. Even though chitosan has applications in almost every sector, it is not completely unlimited in medical application. That's because chitosan's molecular structure is highly crystallinity-rich in hydrogen bonds and so nearly insoluble in water. In the clinical context, hyperosmotic wounds contain an awful lot of mucus so chitosan needs to be more water soluble. It is a general rule that there are three ways to make chitosan water-soluble: 1. deacetylation of chitin; 2. chemical chemistry, adding hydrophilic groups to chitosan molecules to dislodge the crystallinity of their hydrogen bonds; 3. degradation into tiny molecules by enzymes to make it water-soluble.

References

  1. Guo W, et al.; Recent Advances of Chitosan-Based Hydrogels for Skin-Wound Dressings. Gels. 2024, 10(3):175.
  2. Zhao J, et al.; Chitosan-based hydrogel wound dressing: From mechanism to applications, a review. Int J Biol Macromol. 2023, 244:125250.
  3. Xia Y, et al.; Applications of Chitosan and its Derivatives in Skin and Soft Tissue Diseases. Front Bioeng Biotechnol. 2022, 10:894667.
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