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Chitosan in Wound Healing

Since its discovery approximately 200 years ago, chitosan, as a cationic natural polymer, has been widely used as a topical dressing in wound management owing to its hemostatic, stimulation of healing, antimicrobial, nontoxic, biocompatible and biodegradable properties. Chitosan can be used to prevent or treat wound and burn infections not only because of its intrinsic antimicrobial properties, but also by virtue of its ability to deliver extrinsic antimicrobial agents to wounds and burns. It can also be used as a slow-release drug-delivery vehicle for growth factors to improve wound healing. The large number of publications in this area suggests that chitosan will continue to be an important agent in the management of wounds and burns.

Antimicrobial effects of chitosan preparations: a summary of in vitro studies.

Wound-healing effects of chitosan preparations

Wound healing is a specific biological process related to the general phenomenon of growth and tissue regeneration. Wound healing progresses through a series of interdependent and overlapping stages in which a variety of cellular and matrix components act together to re-establish the integrity of damaged tissue and replacement of lost tissue. The wound-healing process has been described as comprising five overlapping stages, which involve complex biochemical and cellular processes. These are described as hemostasis, inflammation, migration, proliferation and maturation phases 

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Newest developments concerning chitosan

In recent years, new forms of chemically modified chitosan have been developed in order to improve the properties of chitosan for various biological activities, and these substances have gained increasing attention. Representative members of these novel polymers include ammonium chitosans, carboxymethyl chitosan and derivatives.

Ammonium chitosan

One factor that limits the application of native chitosan is its non-solubility in neutral and alkaline aqueous solutions. As a result, chitosan derivatives containing quaternary ammonium salts, such as N,N,N-trimethyl chitosan, N-propyl-N,N-dimethyl chitosan and N-furfuryl-N,N-dimethyl chitosan have been investigated for improved solubility in water and subsequently improved biological activities. Studies have shown that all quaternary ammonium chitosan derivatives were highly water-soluble at acidic, basic and neutral pH . Compared with native chitosan, ammonium chitosan demonstrated enhanced antimicrobial properties and drug-delivery abilities .

Carboxymethyl chitosan

Carboxymethyl chitosan (CMC) is another modification of chitosan formed by attaching carboxymethyl groups to the chitosan backbone. Depending on the location of the carboxymethyl group attachment, CMC can be referred to as ‘N’ when the carboxymehthyl group attaches to the amine, ‘O’ when it attaches to the primary hydroxyl group or N,O,-carboxymethyl chitosan when attached to both . CMC has the advantage of a greater solubility range than native chitosan. CMC has now been extensively studied for its activities for drug delivery, hemostasis, antimicrobial action and the stimulation of wound healing .

 

Expert commentary

The main goals of wound care and management are prevention of infection, maintenance of a moist environment, protection of the wound and achievement of rapid and complete healing with the minimum scar formation. Chitosan, as a cationic natural polymer, has been widely used as a topical dressing in wound management owing to its hemostatic, stimulation of healing, antimicrobial, nontoxic, biocompatible and biodegradable properties. In this review, we covered the antimicrobial and wound-healing effects of chitosan preparations for wounds and burns.

With respect to the antimicrobial effects, in-vitro studies have shown that chitosan as well as its derivatives and complexes are active against fungal species such as Candida spp., Gram-positive and Gram-negative bacteria . Generally, chitosan shows stronger antimicrobial effects against Candida spp. and Gram-positive bacteria than it does against Gram-negative bacteria. The proposed antimicrobial mechanisms in Gram-positives include the binding of chitosan to teichoic acids, coupled with a potential extraction of membrane lipids, while in Gram-negatives the cationic structure can displace divalent cations resulting in disruption of lipopolysaccharide binding and permeabilization of the outer membrane. Both these sequences of events (e.g., cell wall disruption) ultimately lead to microbial cell death.

Various animal studies on using chitosan to treat or prevent different types of wound infections have been carried out. The data showed that chitosan rapidly killed the microbial cells in wounds and reduced the mortality of the animals in case of fatal infections. Clinical studies on using chitosan for treating chronic periodontitis reported that chitosan significantly improved the clinical parameters.

With respect to wound-healing effects, it has been indicated from in vitro studies that chitosan enhances the functions of PMN, macrophages and fibroblasts. As a result, chitosan promotes granulation and organization. Most of the animal and clinical studies reported that chitosan preparations accelerate the wound healing. The infiltration of PMN cells and production of fibroblasts are promoted. The number of inflammatory cells in the wound is reduced. In addition, chitosans are nontoxic to normal cells. However, side effects of some chitosan preparations were also reported , and chitosan was also found to be ineffective in corneal wound healing .

With respect to the physical and biological properties, it was concluded from the studies in this review that chitosan, as a wound dressing, must be rapidly and uniformly adherent and conform to wound bed topography and contours to prevent air or fluid pocket formation. The dressing is preferably permeable to water vapor so that a moist exudate under the dressing is maintained without pooling.

The large number of publications in this area suggests that chitosan will continue to be an important agent in the management of wounds and burns.

 

Five-year view

The relentless growth and increasing geographical expansion of antibiotic resistance amongst numerous species of pathogenic bacteria is causing international concern. Coupled with the lack of discovery of new classes of antibiotics, fears are growing that serious wounds and burns may again become life-threatening, as they were in the days before antibiotics were discovered. These concerns have driven a major research effort in both academic laboratories and life science companies to develop alternative antimicrobial strategies and products to which it is hypothesized bacteria will be unable to develop resistance. Topical antimicrobials are a large part of this effort and antimicrobial dressings for wounds and burns that can be used both prophylactically and therapeutically are especially valuable. Since this is precisely the area where the particular qualities of chitosan discussed in the present review are most effective, we see the future potential of chitosan to prevent and treat wound and burn infections as strong. The large and increasing number of publications in this area suggests that chitosan will continue to be an important agent in the management of wounds and burns.

Conclusion

l Chitosan and its derivatives and complexes are active against fungi, Gram-positive and Gram-negative bacteria.

l Chitosan demonstrates efficacy in treating or preventing different types of wound infections.

l Chitosan enhances the functions of polymorphonuclear neutrophils, macrophages and fibroblasts. As a result, chitosan promotes granulation and organization.

l Chitosan, as a wound dressing, must be rapidly and uniformly adherent and conform to wound bed topography and contours to prevent air or fluid pocket formation. The dressing is preferably permeable to water vapor so that a moist exudate under the dressing is maintained without pooling.

l Chitosan and its derivatives are promising materials for controlled drug delivery.

 

 

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