Enhancement of cellular activity in hyperglycemic mice dermal wounds dressed with chitosan-alginate membranes.

J.S.C Breder,Â.M Moraes,S.R Consonni,G.G Adams,S.I Jiwani,E.P Araújo,A.L.R Pires,F.F Azevedo,P.P Apolinário,M.H.M Lima,M.J.A Saad,T Cantaruti

doi:10.1590/1414-431x20198621

Abstract

The use of specially designed wound dressings could be an important alternative to facilitate the healing process of wounds in the hyperglycemic state. Biocompatible dressings combining chitosan and alginate can speed up wound healing by modulating the inflammatory phase, stimulating fibroblast proliferation, and aiding in remodeling phases. However, this biomaterial has not yet been explored in chronic and acute lesions of diabetic patients. The aim of this study was to evaluate the effect of topical treatment with a chitosan-alginate membrane on acute skin wounds of hyperglycemic mice. Diabetes mellitus was induced by streptozotocin (60 mg · kg-1 · day-1 for 5 days, intraperitoneally) and the cutaneous wound was performed by removing the epidermis using a surgical punch. The results showed that after 10 days of treatment the chitosan and alginate membrane (CAM) group exhibited better organization of collagen fibers. High concentrations of interleukin (IL)-1α, IL-1β, granulocyte colony-stimulating factor (G-CSF), and tumor necrosis factor-alpha (TNF-α) were detected in the first and second days of treatment. G-CSF and TNF-α level decreased after 5 days, as well as the concentrations of TNF-α and IL-10 compared with the control group (CG). In this study, the inflammatory phase of cutaneous lesions of hyperglycemic mice was modulated by the use of CAM, mostly regarding the cytokines IL-1α, IL-1β, TNF-α, G-CSF, and IL-10, resulting in better collagen III deposition. However, further studies are needed to better understand the healing stages associated with CAM use.

Highlights

Wound healing is a complex process, being essential for skin repair
In the qualitative analysis performed on the 10th day, the chitosan and alginate membrane (CAM) group showed a more regular and uniform arrangement of type I and III collagen fibers compared to the control group (CG) (Figure 4A), but there was no statistical difference in the quantitative analysis (Figure 4B and C)
The multiplex assays used to determine cytokine levels in the wound area showed that interleukin-1 alpha (IL-1a) (P=0.036) (Figure 5A) and IL-1b (P=0.012) (Figure 5B) were higher in the CAM group compared to the CG on day 1

Summary

Introduction

Wound healing is a complex process, being essential for skin repair. It is basically comprised of three phases: inflammation, proliferation, and maturation, which overlap in time and space [1,2]. Many cell types may be involved in this process, and phenomena as the influx of macrophages, neutrophils, endothelial cells, platelets, keratinocytes, and fibroblasts, as well as the release of cytokines and growth factors, are commonly observed during woundhealing phases [1,2] Cytokines such as interleukin-1 alpha (IL-1a), IL-1b, and tumor necrosis factor-alpha (TNF-a) have a key role in the wound healing process [1,2]. IL-1b and TNF-a, for instance, are produced by macrophages, keratinocytes, vascular endothelial cells, fibroblasts, monocytes, and T lymphocytes in wounds [3] Another factor present in the inflammatory phase of skin lesions is the granulocyte colony stimulating factor (G-CSF), which has the ability to accelerate hematopoiesis in the bone marrow and make these cells available in the bloodstream.

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