Carboxymethyl chitosan hydrogel formulations enhance the healing process in experimental partial-thickness (second-degree) burn wound healing

Gonçalves, Randys Caldeira; Signini, Roberta; Rosa, Luciana Martins; Dias, Yuri Santana Pereira; Vinaud, Marina Clare; Lino Junior, Ruy de Souza

doi:10.1590/ACB360303

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Acta Cirúrgica Brasileira

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Sumário

ORIGINAL ARTICLE • Acta Cir. Bras. 36 (3) • 2021 • https://doi.org/10.1590/ACB360303 copy

Carboxymethyl chitosan hydrogel formulations enhance the healing process in experimental partial-thickness (second-degree) burn wound healing

Authorship SCIMAGO INSTITUTIONS RANKINGS

ABSTRACT

Purpose

This study aimed to elaborate a hydrogel constituted by carboxymethyl chitosan (CMC), hyaluronic acid (HA) and silver (Ag) and to evaluate its healing effect on partial-thickness burn wounds experimentally induced in rats.

Methods

CMC was obtained by chitosan reacting with monochloroacetic acid. The carboxymethylation was confirmed by Fourier-transform infrared spectroscopy and hydrogen nuclear magnetic resonance (NMR). Scanning electron microscopy was used to determine the morphologicalcharacteristics of chitosan and CMC. After the experimental burn wound induction, the animals (n = 126) were treated with different CMC formulations, had their occlusive dressings changed daily and were followed through 7, 14 and 30 days. Morphometric, macroscopic and microscopic aspects and collagen quantification were evaluated.

Results

Significative wound contraction, granulation tissue formation, inflammatory infiltration and collagen fibers deposit throughout different phases of the healing process were observed in the CMC hydrogels treated groups.

Conclusions

The results showed that, in the initial phase of the healing process, the most adequate product was the CMC/HA/Ag association, while in the other phases the CMC/HA association was the best one to promote the healing of burn wounds.

Key words
Hydrogels; Carboxymethyl Chitosan; Experimental Burn Wound; Rats; General Pathologic Processes

	DAI	Control (n = 18)			Hydrogels (n = 18)				p	Dunn’s
	DAI	PS	SS	Hy	CMC	CMC/HA	CMC/Ag	CMC/HA/Ag	p	Dunn’s
Necrosis/crust	7	3 (2–3)	0 (0–1)	3 (3–3)	3 (2–3)	3 (2–3)	2.5 (2–3)	3 (3–3)	< 0.001^* * p < 0.05.	Hy > SS CMC/HA/Ag > SS PS > SS CMC/HA > SS CMC > SS CMC/Ag > SS
	14	2 (1–3)	1 (0–2)	0 (0–2)	0.5 (0–1)	0.5 (0–1)	1.5 (0–3)	0 (0–1)	0.027^* * p < 0.05.	PS > CMC/HA/Ag PS > CMC/HA PS > CMC PS > Hy
	30	2 (2–3)	0 (0–1)	0 (0–0)	0 (0–1)	0 (0–0)	0 (0–1)	0 (0–0)	< 0.001^* * p < 0.05.	PS > CMC/HA/Ag PS > CMC/HA PS > Hy PS > CMC/Ag PS > SS PS > CMC
Granulation tissue	7	2 (1–2)	0 (10–0)	0 (0–0)	0 (0–1)	0 (0–1)	1 (0–2)	0 (0–1)	< 0.001^* * p < 0.05.	PS > Hy PS > SS PS > CMC/HA/Ag PS > CMC/HA PS > CMC CMC/Ag > Hy CMC/Ag > SS CMC/Ag > CMC/HA/Ag CMC/Ag > CMC/HA CMC/Ag > CMC
	14	2.5 (2–3)	1 (0–2)	3 (3–3)	3 (3–3)	3 (3–3)	2 (1–3)	3 (2–3)	> 0.001^* * p < 0.05.	Hy > SS CMC > SS CMC/HA > SS CMC/HA/Ag > SS PS > SS
	30	0 (0–0)	1 (0–1)	0 (0–0)	0 (0–0)	0 (0–0)	0 (0–0)	0 (0–0)	> 0.001^* * p < 0.05.	SS > CMC/HA/Ag SS > CMC/HA SS > CMC/Ag SS > CMC SS > Hy SS > PS
Re-epithelialization	7	0 (0–0)	0 (0–0)	0 (0–0)	0 (0–0)	0 (0–0)	0 (0–0)	0 (0–0)	1
	14	0.5 (0–2)	0 (0–1)	1 (1–1)	1 (0–1)	1 (0–1)	0 (0–1)	1 (0–1)	0.126
	30	3 (2–3)	3 (3–3)	3 (3–3)	3 (3–3)	3 (3–3)	3 (3–3)	3 (3–3)	0.022^* * p < 0.05.	CMC > PS CMC/HA > PS CMC/Ag > PS CMC/HA/Ag > PS SS > PS Hy > PS

Pathologic processes	DAI	Control (n = 18)			Hydrogels (n = 18)				p	Dunn’s
Pathologic processes	DAI	PS	SS	Hy	CMC	CMC/HA	CMC/Ag	CMC/HA/Ag	p	Dunn’s
PMN infiltration	7	2 (1–3)	1 (1–2)	3 (3–3)	2 (1–3)	3 (2–3)	3 (3–3)	3 (3–3)	0.001	CMC/Ag > SS CMC/Ag > PS CMC/HA/Ag > SS CMC/HA/Ag > PS HY > SS HY > PS CMC/HA > SS
	14	1 (1–1)	2 (1–3)	1 (0–1)	1 (1–2)	1 (1–1)	1 (1–1)	2 (1–2)	0.005	SS > HY CMC/HA/Ag > Hy
	30	1 (1–0)	1 (0–1)	0 (0–0)	1 (1–2)	0 (0–0)	1 (0–2)	0 (0–1)	0.009	CMC > Hy CMC > CMC/HA CMC > PS
MN infiltration	7	2 (2–3)	3 (3–3)	2 (2–3)	2 (2–3)	2 (2–2)	3 (3–3)	2 (2–3)	0.002	SS > CMC/HA SS > CMC/HA/AG CMC/Ag > CMC/HA CMC/Ag > CMC/HA/Ag
	14	2 (2–3)	2 (2–2)	2 (1–2)	3 (2–30)	3 (2–3)	2 (2–3)	3 (2–3)	0.088
	30	1 (1–2)	2 (1–2)	1 (1–1)	2 (1–2)	1 (0–1)	1 (1–2)	1 (1–2)	0.102
Angiogenesis	7	3 (3–3)	3 (3–3)	3 (3–3)	3 (3–3)	3 (3–3)	3 (3–3)	3 (3–3)	1
	14	3 (2–3)	2 (2–2)	3 (2–3)	3 (3–3)	3 (3–3)	3 (3–3)	3 (3–3)	0.001	CMC > SS CMC/HA > SS CMC/Ag > SS CMC/HA/Ag > SS PS > SS Hy > SS
	30	1 (1–1)	1 (1–2)	1 (1–1)	2 (1–2)	2 (2–2)	2 (1–3)	2 (1–3)	0.010	CMC/Ag > Hy CMC/Ag > PS

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[1] *Corresponding author: ruy@ufg.br | (55 62)3209-6163