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This is linked to the end of the healing process and decrease of inflammation infiltrate into the wound zone (Figure 8).

Discussion

  Many studies have demonstrated the therapeutic properties of chitosan (eg, dressings or scaffolds for tissue engineering).^2,4 However, the effects of chitosan on angiogenesis remain unclear.^16,17 The present study found that chitosan enhances angiogenesis and NO release. In addition, the chitosan treated burns yielded positive effects on the overall healing response. The use of chitosan to cover burn wounds may accelerate healing by inhibiting water loss, since it creates a layer of high adherence capacity on the wound, and stimulates a higher infiltration of PMNs. The infiltration and migration of PMNs during the first days of healing is an important event in the complex process of tissue repair. This event is triggered at the beginning of the healing process by the release of several growth factors contained in the platelets.¹⁸ Chitosan plays an important role in adhesion, aggregation, and platelet-leukocyte aggregation agent.¹⁹ In-vitro studies revealed that and large amounts of leucotriens and prostaglandins in chitosan-treated wound exudates due to increase the PMN’s infiltration and macrophages containing inflammation mediators and stimulates phagocytosis.^4,7,20,21 Histopathological samples taken from burn area revealed that acute inflammation peaked at post-burn day 14 in both groups. However, the chitosan group’s score was higher. Chronic inflammation peaked at post-burn day 7 in both groups. The control group had the highest score for chronic inflammation. Ueno et al²² suggest that chitosan enhances the functions of inflammatory cells, such as PMNs stimulating phagocytosis and production of osteopontin and leukotriene β4; macrophages increased the production of interleukin-1, TGF-b1, and platelet-derived growth factor (PDGF); and fibroblasts increased the production of IL-8. With the results shown for acute inflammation and chronic inflammation, it is possible to associate these with the highest score in collagen deposit and granulation tissue in the chitosan group.

  Increased inflammatory reaction causes more collagen production and scar formation due to the increased number of fibroblasts.²³ It has been reported that chitin- and chitosan-treated wounds have a higher collagen deposit from day 4.²⁴ The present study associated chitosan with higher collagen deposits versus control beginning on day 14.^25,26 While the present study did not directly measure different collagen types, the results concur with immunohistochemical studies that demonstrated an increase in type III collagen after day 3.²² Also Kojima et al²⁴ determined indirectly the synthesis of collagen, using the enzyme prolyl-hidroxylase, showed a high level of activity after 7 day of treatment in chitosan-treated wounds. The present study had similar results between days 7 and 14, and a higher collagen deposit was observed in treated burns as opposed to controls, which was directly associated with dermis reconstruction and the decrease in burn size.

 &Nbsp;There are several mediators associated with cell infiltration that can influence the cellular infiltrate and modified wound healing process, one of which is NO.