Chitosan preparations for wounds and burns: antimicrobial and wound-healing effects

Abstract

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. This article covers the antimicrobial and wound-healing effects of chitosan, as well as its derivatives and complexes, and its use as a vehicle to deliver biopharmaceuticals, antimicrobials and growth factors into tissue. Studies covering applications of chitosan in wounds and burns can be classified into in vitro, animal and clinical studies. Chitosan preparations are classified into native chitosan, chitosan formulations, complexes and derivatives with other substances. 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.

Figure 1. Preparation of chitosan from chitin

(A) Preparation of chitosan from chitin by alkaline deacetylation. (B) Preparation of chitosan from chitin by enzymatic deacetylation.

Figure 2

Schematic depiction of the applications of chitosan in wound-healing and burn therapy, showing it can be usefully applied ‘from head to toe’.

Figure 3. Treatment of mouse burn infections using a chitosan acetate bandage

(A) Representative successive bioluminescence images from days 0–3 of mice with Pseudomonas aeruginosa-infected burns with no treatment, treated with silver dressing and treated with chitosan acetate bandage. The inset at day 3 in silver dressing burn shows the bioluminescence signal after the dressing was removed from a dead mouse. (B) Survival curves of mice with P. aeruginosa-infected burns treated with chitosan acetate bandage (n = 15), silver dressing (n = 11) or no treatment (n = 15). (C) Survival curves of mice with Proteus mirabilis-infected burn treated with chitosan acetate bandage (n = 12), silver dressing (n = 8) or no treatment (n = 13). Reprinted from [21] with permission.

Figure 4. The phases of cutaneous wound healing

(A) Immediately following cutaneous injury, blood elements and amines extravasate from locally damaged blood vessels within the dermis. Vascular permeability is temporarily increased to allow neutrophils (PMNs), platelets and plasma proteins to infiltrate the wound. Vasoconstriction follows, in response to factors released by these cells. (B) Coagulation then occurs as platelets aggregate with fibrin, which is deposited in the wound following its conversion from fibrinogen. (C) Platelets release several factors, including PDGF and TGF-β, which attract PMNs to the wound, signaling the beginning of inflammation. (D) After 48 h, macrophages replace PMNs as the principal inflammatory cell. Together, PMNs and macrophages remove debris from the wound, release growth factors and begin to reorganize the extracellular matrix. (E) The proliferation phase begins at about 72 h as fibroblasts, recruited to the wound by growth factors released by inflammatory cells, begin to synthesize collagen, and angiogenesis and re-epitheliazation occurs. (F) Collagen crosslinking and reorganization occur for months after injury in the remodeling phase of repair. Chitosan has been reported to beneficially influence stages (B–E). PMN: Polymorphonuclear leukocyte. Reproduced with permission from [108].