Amelioration of full-thickness cutaneous wound healing using stem cell exosome and zinc oxide nanoparticles in rats

Background: Wound healing is a complex procedure that requires the coordination of several factors, so this study aimed to assess the zinc oxide nanoparticles’ regenerated effect and stem cell exosomes on full-thickness wounds in rats. Methods: Seventy-two Wistar male rats were subjected to a full-t...

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Main Authors: Mohamed Salem, Ahmed Ateya, Zeinab Shouman, Basma Salama, Basma Hamed, Gaber Batiha, Farid Ataya, Athanasios Alexiou, Marios Papadakis, Marwa Abass
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Language:English
Published: Elsevier 2024-11-01
Series:Heliyon
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Online Access:http://www.sciencedirect.com/science/article/pii/S2405844024150256
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author Mohamed Salem
Ahmed Ateya
Zeinab Shouman
Basma Salama
Basma Hamed
Gaber Batiha
Farid Ataya
Athanasios Alexiou
Marios Papadakis
Marwa Abass
author_facet Mohamed Salem
Ahmed Ateya
Zeinab Shouman
Basma Salama
Basma Hamed
Gaber Batiha
Farid Ataya
Athanasios Alexiou
Marios Papadakis
Marwa Abass
author_sort Mohamed Salem
collection DOAJ
description Background: Wound healing is a complex procedure that requires the coordination of several factors, so this study aimed to assess the zinc oxide nanoparticles’ regenerated effect and stem cell exosomes on full-thickness wounds in rats. Methods: Seventy-two Wistar male rats were subjected to a full-thickness skin defect (20 mm2) on the dorsal surface of each rat between two shoulder joints. The rats were randomized into four groups (18/group) according to wound treatments. The wounds were irrigated with normal saline (Control group), or the wound's edges were subcutaneously injected daily with 0.3 ml of exosome (Exo-group), or 1 ml of zinc oxide nanoparticles (ZnO2-NPs group), or 0.3 ml of exosome in combined with 1 ml of zinc oxide nanoparticles (Exo/ZnO2-NPs group). On the 7th, 14th, and 21st days post-wounding, the weight of the rats, the wound healing breaking strength, the wound size, and the contraction percent were evaluated. Six rats in each group were euthanized at each time point for histopathological, immunohistochemical examination of collagen, the levels of alpha-smooth muscle actin (α-SMA), and epidermal growth factor receptor (EGFR). additionally, the gene expression analysis of the relative renal nuclear factor erythroid 2-related factor2 (Nrf2 mRNA), Transforming growth factor beta-1 (TGFβ1), fibroblast growth factor-7 (FGF7), Transforming growth factor beta-1 (TGFβ1), Lysyl oxidase (LOX), and Vascular endothelial growth factor (VEGF) were applied. Results: The Exo-group exhibited a significant decrease in wound size and a significant increase in wound contraction compared with other groups. Histopathologically evaluation during the three intervals revealed that the Exo-group had the highest collagen deposition area with a significant reduction of the granulation tissue. Moreover, upregulated gene expression profiles of the growth factors genes at all time points post-wounding. Discussion: The exosomes-treated group revealed superior wound healing and contraction, with minimal inflammatory signs, higher angiogenesis, and myofibroblasts, and associated with higher growth factor expression genes compared to the other groups. Conclusions: Exosome-based therapy demonstrates potential as a treatment method to promote and accelerate wound healing by modulating angiogenesis, re-epithelialization, collagen deposition, and gene expression profiles.
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spelling doaj-art-796205e8b1234dba9bb98896f547e7f32024-11-15T06:12:31ZengElsevierHeliyon2405-84402024-11-011021e38994Amelioration of full-thickness cutaneous wound healing using stem cell exosome and zinc oxide nanoparticles in ratsMohamed Salem0Ahmed Ateya1Zeinab Shouman2Basma Salama3Basma Hamed4Gaber Batiha5Farid Ataya6Athanasios Alexiou7Marios Papadakis8Marwa Abass9Department of Surgery, Anesthesiology, and Radiology, Faculty of Veterinary Medicine, Mansoura University, Mansoura, 35516, Egypt; Department of Veterinary Clinical Sciences, Faculty of Veterinary Medicine, Jordan University of Science and Technology, Irbid, 22110, JordanDepartment of Development of Animal Wealth, Faculty of Veterinary Medicine, Mansoura University, Mansoura, 35516, EgyptDepartment of Cytology and Histology, Faculty of Veterinary Medicine, Mansoura University, Mansoura, 35516, EgyptDepartment of Biochemistry and Molecular Biology, Faculty of Veterinary Medicine, Mansoura University, Mansoura, 35516, EgyptMansoura experimental research center (MERC), Faculty of Medicine, Mansoura, 35516, EgyptDepartment of Pharmacology and Therapeutics, Faculty of Veterinary Medicine, Damanhour University, Damanhour 22511, AlBeheira, EgyptDepartment of Biochemistry, College of Science, King Saud University, PO Box 2455, Riyadh, 11451, Saudi ArabiaDepartment of Research & Development, Funogen, Athens, 11741, Greece; University Centre for Research & Development, Chandigarh University, Chandigarh-Ludhiana Highway, Mohali, Punjab, IndiaDepartment of Surgery II, University Hospital Witten-Herdecke, Heusnerstrasse 40, University of Witten-Herdecke, 42283, Wuppertal, GermanyDepartment of Surgery, Anesthesiology, and Radiology, Faculty of Veterinary Medicine, Mansoura University, Mansoura, 35516, Egypt; Corresponding author. Department of Surgery, Anesthesiology, and Radiology, Faculty of Veterinary Medicine, Mansoura University, Mansoura, 35516, Egypt.Background: Wound healing is a complex procedure that requires the coordination of several factors, so this study aimed to assess the zinc oxide nanoparticles’ regenerated effect and stem cell exosomes on full-thickness wounds in rats. Methods: Seventy-two Wistar male rats were subjected to a full-thickness skin defect (20 mm2) on the dorsal surface of each rat between two shoulder joints. The rats were randomized into four groups (18/group) according to wound treatments. The wounds were irrigated with normal saline (Control group), or the wound's edges were subcutaneously injected daily with 0.3 ml of exosome (Exo-group), or 1 ml of zinc oxide nanoparticles (ZnO2-NPs group), or 0.3 ml of exosome in combined with 1 ml of zinc oxide nanoparticles (Exo/ZnO2-NPs group). On the 7th, 14th, and 21st days post-wounding, the weight of the rats, the wound healing breaking strength, the wound size, and the contraction percent were evaluated. Six rats in each group were euthanized at each time point for histopathological, immunohistochemical examination of collagen, the levels of alpha-smooth muscle actin (α-SMA), and epidermal growth factor receptor (EGFR). additionally, the gene expression analysis of the relative renal nuclear factor erythroid 2-related factor2 (Nrf2 mRNA), Transforming growth factor beta-1 (TGFβ1), fibroblast growth factor-7 (FGF7), Transforming growth factor beta-1 (TGFβ1), Lysyl oxidase (LOX), and Vascular endothelial growth factor (VEGF) were applied. Results: The Exo-group exhibited a significant decrease in wound size and a significant increase in wound contraction compared with other groups. Histopathologically evaluation during the three intervals revealed that the Exo-group had the highest collagen deposition area with a significant reduction of the granulation tissue. Moreover, upregulated gene expression profiles of the growth factors genes at all time points post-wounding. Discussion: The exosomes-treated group revealed superior wound healing and contraction, with minimal inflammatory signs, higher angiogenesis, and myofibroblasts, and associated with higher growth factor expression genes compared to the other groups. Conclusions: Exosome-based therapy demonstrates potential as a treatment method to promote and accelerate wound healing by modulating angiogenesis, re-epithelialization, collagen deposition, and gene expression profiles.http://www.sciencedirect.com/science/article/pii/S2405844024150256ExosomeZinc nanoparticlesSkin woundRatsGene expression
spellingShingle Mohamed Salem
Ahmed Ateya
Zeinab Shouman
Basma Salama
Basma Hamed
Gaber Batiha
Farid Ataya
Athanasios Alexiou
Marios Papadakis
Marwa Abass
Amelioration of full-thickness cutaneous wound healing using stem cell exosome and zinc oxide nanoparticles in rats
Heliyon
Exosome
Zinc nanoparticles
Skin wound
Rats
Gene expression
title Amelioration of full-thickness cutaneous wound healing using stem cell exosome and zinc oxide nanoparticles in rats
title_full Amelioration of full-thickness cutaneous wound healing using stem cell exosome and zinc oxide nanoparticles in rats
title_fullStr Amelioration of full-thickness cutaneous wound healing using stem cell exosome and zinc oxide nanoparticles in rats
title_full_unstemmed Amelioration of full-thickness cutaneous wound healing using stem cell exosome and zinc oxide nanoparticles in rats
title_short Amelioration of full-thickness cutaneous wound healing using stem cell exosome and zinc oxide nanoparticles in rats
title_sort amelioration of full thickness cutaneous wound healing using stem cell exosome and zinc oxide nanoparticles in rats
topic Exosome
Zinc nanoparticles
Skin wound
Rats
Gene expression
url http://www.sciencedirect.com/science/article/pii/S2405844024150256
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