Melatonin associated with bacterial cellulose-based hydrogel improves healing of skin wounds in diabetic rats

Silva, Jaiurte Gomes Martins da; Melo, Ismaela Maria Ferreira de; Alves, Érique Ricardo; Oliveira, Glícia Maria de; Silva, Anderson Arnaldo da; Pinto, Flávia Cristina Morone; Aguiar, José Lamartine de Andrade; Araújo, Diego Neves; Teixeira, Valéria Wanderley; Teixeira, Álvaro Aguiar Coelho

doi:10.1590/acb399024

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Original Article • Acta Bras Cir 39 • 2024 • https://doi.org/10.1590/acb399024 linkcopy

Melatonin associated with bacterial cellulose-based hydrogel improves healing of skin wounds in diabetic rats

Authorship SCIMAGO INSTITUTIONS RANKINGS

Purpose: To describe the effects of melatonin associated with bacterial cellulose-based hydrogel on healing of skin wounds in diabetic rats.

Methods: Streptozotocin was used to induce diabetes in Wistar rats. After wound induction, animals were randomly divided into groups GC, GDCC, GDCB, and GDMCB. Animals were evaluated in days 3, 7, and 14 for the following variables: glycemic levels, histopathological and histochemical analyses, healing rate, morphometry and C-reactive protein.

Results: There was no change in glycemic levels in the diabetic animals as a result of the treatments; histopathological analyses showed better healing in GDCB and GDMCB groups, as well as histochemistry; at day 14, the highest healing rate was observed in animals from the GDMCB group, reaching almost 100%; morphometry revealed a significant increase of fibroblasts and reduction of macrophages and blood vessels in lesions treated with bacterial cellulose associated or not with melatonin when compared to the other experimental groups. There was also an increase in C-reactive protein in GDCC group at day 14.

Conclusion: Bacterial cellulose-based dressings associated with systemic melatonin showed beneficial results in experimentally induced wounds in diabetic rats, favoring the healing process.

Key words
Biopolymers; Diabetes Mellitus; Bandages; Melatonin; Histology

Authorship

person Jaiurte Gomes Martins da Silva *

Conception and design · Acquisition of data · Statistical analysis · Manuscript writing · Critical revision · Final approval of the version to be published PhDs

schoolUniversidade Federal Rural de Pernambuco – Department of Animal Morphology and Physiology – Graduate Program in Animal Bioscience – Recife (PE) – Brazil.Universidade Federal Rural de PernambucoBrazilRecife, PE, BrazilUniversidade Federal Rural de Pernambuco – Department of Animal Morphology and Physiology – Graduate Program in Animal Bioscience – Recife (PE) – Brazil.schoolUniversidade Federal de Alagoas – Maceió (AL) – Brazil.Universidade Federal de AlagoasBrazilMaceió, AL, BrazilUniversidade Federal de Alagoas – Maceió (AL) – Brazil.

0000-0002-6310-1023

person Ismaela Maria Ferreira de Melo

Acquisition of data · Manuscript writing · Final approval of the version to be published PhDs

0000-0002-4150-1923

person Érique Ricardo Alves

Acquisition of data · Statistical analysis PhDs

0000-0002-7925-9212

person Glícia Maria de Oliveira

Acquisition of data · Manuscript writing · Critical revision

schoolUniversidade Federal de Pernambuco – Department of Biochemistry – Graduate Program in Therapeutic Innovation – Recife (PE) – Brazil.Universidade Federal de PernambucoBrazilRecife, PE, BrazilUniversidade Federal de Pernambuco – Department of Biochemistry – Graduate Program in Therapeutic Innovation – Recife (PE) – Brazil.

0000-0002-4415-5931

person Anderson Arnaldo da Silva

Acquisition of data · Critical revision PhDs

schoolUniversidade Federal de Pernambuco – Graduate Program in Biosciences and Biotechnology in Health – Recife (PE) – Brazil.Universidade Federal de PernambucoBrazilRecife, PE, BrazilUniversidade Federal de Pernambuco – Graduate Program in Biosciences and Biotechnology in Health – Recife (PE) – Brazil.

0000-0002-2727-6838

person Flávia Cristina Morone Pinto

Conception and design · Critical revision PhDs

schoolUniversidade Federal de Pernambuco – Department of Surgery – Graduate Program in Surgery – Recife (PE) – Brazil.Universidade Federal de PernambucoBrazilRecife, PE, BrazilUniversidade Federal de Pernambuco – Department of Surgery – Graduate Program in Surgery – Recife (PE) – Brazil.

0000-0001-9196-7687

person José Lamartine de Andrade Aguiar

Conception and design · Critical revision PhDs

0000-0003-4493-7359

person Diego Neves Araújo

Statistical analysis · Manuscript writing PhDs

schoolUniversidade Federal de Alagoas – Maceió (AL) – Brazil.Universidade Federal de AlagoasBrazilMaceió, AL, BrazilUniversidade Federal de Alagoas – Maceió (AL) – Brazil.

0000-0002-9541-5852

person Valéria Wanderley Teixeira

Conception and design · Statistical analysis · Critical revision PhDs

0000-0001-9533-5476

person Álvaro Aguiar Coelho Teixeira

Conception and design · Statistical analysis · Critical revision PhDs

0000-0001-5940-9220

person* Corresponding author:
emailjaiurte.silva@arapiraca.ufal.br

Section editor: Maria de Lourdes Biondo-Simões https://orcid.org/0000-0001-7056-8142

Conflict of interest

Nothing to declare.

SCIMAGO INSTITUTIONS RANKINGS

Universidade Federal Rural de Pernambuco – Department of Animal Morphology and Physiology – Graduate Program in Animal Bioscience – Recife (PE) – Brazil.Universidade Federal Rural de PernambucoBrazilRecife, PE, BrazilUniversidade Federal Rural de Pernambuco – Department of Animal Morphology and Physiology – Graduate Program in Animal Bioscience – Recife (PE) – Brazil.

Universidade Federal de Alagoas – Maceió (AL) – Brazil.Universidade Federal de AlagoasBrazilMaceió, AL, BrazilUniversidade Federal de Alagoas – Maceió (AL) – Brazil.

Universidade Federal de Pernambuco – Department of Biochemistry – Graduate Program in Therapeutic Innovation – Recife (PE) – Brazil.Universidade Federal de PernambucoBrazilRecife, PE, BrazilUniversidade Federal de Pernambuco – Department of Biochemistry – Graduate Program in Therapeutic Innovation – Recife (PE) – Brazil.

Universidade Federal de Pernambuco – Graduate Program in Biosciences and Biotechnology in Health – Recife (PE) – Brazil.Universidade Federal de PernambucoBrazilRecife, PE, BrazilUniversidade Federal de Pernambuco – Graduate Program in Biosciences and Biotechnology in Health – Recife (PE) – Brazil.

Universidade Federal de Pernambuco – Department of Surgery – Graduate Program in Surgery – Recife (PE) – Brazil.Universidade Federal de PernambucoBrazilRecife, PE, BrazilUniversidade Federal de Pernambuco – Department of Surgery – Graduate Program in Surgery – Recife (PE) – Brazil.

Figures | Formulas

Figures (10)
Formulas (1)

Thumbnail

Figure 1 Mean + standard deviation of glycemic levels in animals in experimental groups. Means followed by the same letters do not differ significantly by Tukey and Kramer’s multiple test (p < 0.05).

Thumbnail

Figure 2 Photograph of the evolution of the cutaneous lesions in the animals of the experimental groups.

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Figure 3 Mean + standard deviation of percentage healing rate of lesions in animals in experimental groups. Means followed by the same letters in the columns do not differ significantly by Tukey and Kramer’s multiple test (p < 0.05).

Thumbnail

Figure 4 Photomicrograph of skin lesions in animals from experimental groups after three days of induction and respective treatments. (a) GC; (b) GDCC, (c) GDCB, (d) GDMCB. Note the presence of granulation tissue (gt) and blood vessels (arrows) in the lesions. Hematoxylin and eosin.

Thumbnail

Figure 5 Photomicrograph of skin lesions in animals from experimental groups after seven days of induction and respective treatments. (a) GC; (b) GDCC, (c) GDCB, (d) GDMCB. Note the presence of granulation tissue (gt) and re-epithelialization in the lesions (arrowhead). Hematoxylin and eosin.

Thumbnail

Figure 6 Photomicrograph of skin lesions in animals from experimental groups after 14 days of induction and respective treatments. (a) GC; (b) GDCC, (c) GDCB, (d) GDMCB. Note in the lesions the presence of granulation tissue (gt) only in a and b, re-epithelialization (arrowhead) and epithelium in the process of keratinization (dashed arrow). Hematoxylin and eosin.

Thumbnail

Figure 7 Masson’s trichrome histochemistry in skin lesions evaluated 14 days after induction and respective treatments. (a) GC; (b) GDCC, (c) GDCB, (d) GDMCB. Note positive labeling in all groups.

Thumbnail

Figure 8 Mean + standard deviation of total collagen quantification in pixels in the skin lesions of animals in the experimental groups. Check a significant increase in GDCB and GDMCB groups. Means followed by the same letters in the columns do not differ significantly by Tukey and Kramer’s multiple test (p < 0.05).

Thumbnail

Figure 9 Mean + standard deviation of the percentage of fibroblasts, macrophages and blood vessels in the skin lesions of the animals in the experimental groups at day 14. Means followed by the same letter do not differ significantly by Tukey and Kramer’s multiple comparisons test (p > 0.05).

Thumbnail

Figure 10 Mean + standard deviation of CRP levels in animals from experimental groups at day 14. Means followed by the same letter do not differ significantly by Tukey and Kramer’s multiple comparisons test (p > 0.05).

Thumbnail

(1)

imageFigure 1 Mean + standard deviation of glycemic levels in animals in experimental groups. Means followed by the same letters do not differ significantly by Tukey and Kramer’s multiple test (p < 0.05). open_in_new

GC: non-diabetic rats; GDCC: diabetic rats treated with amorphous commercial healing agent with alginate; GDCB: diabetic rats treated with bacterial cellulose; GDMCB: diabetic rats treated with melatonin and bacterial cellulose. Source: Elaborated by the authors.

imageFigure 2 Photograph of the evolution of the cutaneous lesions in the animals of the experimental groups. open_in_new

imageFigure 3 Mean + standard deviation of percentage healing rate of lesions in animals in experimental groups. Means followed by the same letters in the columns do not differ significantly by Tukey and Kramer’s multiple test (p < 0.05). open_in_new

imageFigure 4 Photomicrograph of skin lesions in animals from experimental groups after three days of induction and respective treatments. (a) GC; (b) GDCC, (c) GDCB, (d) GDMCB. Note the presence of granulation tissue (gt) and blood vessels (arrows) in the lesions. Hematoxylin and eosin. open_in_new

imageFigure 5 Photomicrograph of skin lesions in animals from experimental groups after seven days of induction and respective treatments. (a) GC; (b) GDCC, (c) GDCB, (d) GDMCB. Note the presence of granulation tissue (gt) and re-epithelialization in the lesions (arrowhead). Hematoxylin and eosin. open_in_new

imageFigure 6 Photomicrograph of skin lesions in animals from experimental groups after 14 days of induction and respective treatments. (a) GC; (b) GDCC, (c) GDCB, (d) GDMCB. Note in the lesions the presence of granulation tissue (gt) only in a and b, re-epithelialization (arrowhead) and epithelium in the process of keratinization (dashed arrow). Hematoxylin and eosin. open_in_new

imageFigure 7 Masson’s trichrome histochemistry in skin lesions evaluated 14 days after induction and respective treatments. (a) GC; (b) GDCC, (c) GDCB, (d) GDMCB. Note positive labeling in all groups. open_in_new

imageFigure 8 Mean + standard deviation of total collagen quantification in pixels in the skin lesions of animals in the experimental groups. Check a significant increase in GDCB and GDMCB groups. Means followed by the same letters in the columns do not differ significantly by Tukey and Kramer’s multiple test (p < 0.05). open_in_new

imageFigure 9 Mean + standard deviation of the percentage of fibroblasts, macrophages and blood vessels in the skin lesions of the animals in the experimental groups at day 14. Means followed by the same letter do not differ significantly by Tukey and Kramer’s multiple comparisons test (p > 0.05). open_in_new

imageFigure 10 Mean + standard deviation of CRP levels in animals from experimental groups at day 14. Means followed by the same letter do not differ significantly by Tukey and Kramer’s multiple comparisons test (p > 0.05). open_in_new

(1)

Healing rate (%) = 1 - \{[{Area}_{1} - {Area}_{n}] / Area\} \times 100

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