Chitosan-based copper nanocomposite accelerates healing in excision wound model in rats
Abstract
Copper possesses efficacy in wound healing which is a complex phenomenon involving various cells, cytokines and growth factors. Copper nanoparticles modulate cells, cytokines and growth factors involved in wound healing in a better way than copper ions. Chitosan has been shown to be beneficial in healing because of its antibacterial, antifungal, biocompatible and biodegradable polymeric nature. In the present study, chitosan-based copper nanocomposite (CCNC) was prepared by mixing chitosan and copper nanoparticles. CCNC was applied topically to evaluate its wound healing potential and to study its effects on some important components of healing process in open excision wound model in adult Wistar rats. Significant increase in wound contraction was observed in the CCNC-treated rats. The up-regulation of vascular endothelial growth factor (VEGF) and transforming growth factor-beta1(TGF-β1) by CCNC-treatment revealed its role in facilitating angiogenesis, fibroblast proliferation and collagen deposition. The tumor necrosis factor-α (TNF-α) and interleukin-10 (IL-10) were significantly decreased and increased, respectively, in CCNC-treated rats. Histological evaluation showed more fibroblast proliferation, collagen deposition and intact re-epithelialization in CCNC-treated rats. Immunohistochemistry of CD31 revealed marked increase in angiogenesis. Thus, we concluded that chitosan-based copper nanocomposite efficiently enhanced cutaneous wound healing by modulation of various cells, cytokines and growth factors during different phases of healing process.
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Copper-containing biomaterials consistently demonstrate enhanced healing of non-infected wounds in animal models compared to controls.
“These studies consistently demonstrate enhanced healing of non-infected wounds [71,72,73,74,75,76], including those in diabetic [77,78,79,80,81,82,83] and burn-related [84,85,86,87,88,89,90] animal models when compared to control materials.”
From The Journey of Copper-Impregnated Dressings in Wound Healing: From a Medical Hypothesis to Clinical Practice (2025) · cites this paper as [75]
Copper-treated wounds show significant increase in VEGF and number of blood vessels compared to controls.
“One of the notorious effects noticed in some of these studies was the significant increase in VEGF and the number of blood vessels in the copper-treated wounds as compared to the controls [72,73,75,77,78,84,97,103].”
From The Journey of Copper-Impregnated Dressings in Wound Healing: From a Medical Hypothesis to Clinical Practice (2025) · cites this paper as [75]
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Molecular mechanisms of enhanced wound healing by copper oxide-impregnated dressings
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Recent progress in metal-organic frameworks-based hydrogels and aerogels and their applications
Wang, L., Xu, H., Gao, J., Yao, J., & Zhang, Q. (2019) · Coordination Chemistry Reviews · doi:10.1016/j.ccr.2019.213016 · Cited by 594 · see citing works
The neglected role of copper ions in wound healing
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Healing of Chronic Wounds by Copper Oxide-Impregnated Wound Dressings—Case Series
Melamed, E., Kiambi, P., Okoth, D., Honigber, I., Tamir, E., & Borkow, G. (2021) · Medicina · doi:10.3390/medicina57030296 · Cited by 55 · see citing works
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- Authors
- Gopal, A., Kant, V., Gopalakrishnan, A., Tandan, S. K., & Kumar, D.
- Affiliations
- Indian Veterinary Research Institute (IN)
- Corresponding author
- Kumar, Dinesh
- Venue
- European Journal of Pharmacology
- Publisher
- Elsevier BV
- Published
- 2014-05
- Volume
- 731
- Pages
- 8-19
- ISSN
- 0014-2999 (ISSN-L)
- OpenAlex
- W2007553156
- Cited by
- 217
- References
- 2
- Citations by year
- 2026: 8 · 2025: 18 · 2024: 29 · 2023: 30 · 2022: 27 · 2021: 20 · 2020: 31 · 2019: 15 · 2018: 12 · 2017: 9 · 2016: 8 · 2015: 7 · 2014: 3
- FWCI
- 8.74
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- European Journal of Pharmacology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Rehabilitation › Wound Healing and Treatments
- Physical Sciences › Materials Science › Biomaterials › Electrospun Nanofibers in Biomedical Applications
- Physical Sciences › Materials Science › Materials Chemistry › Nanoparticles: synthesis and applications
- Keywords
- chitosan, copper nanoparticles, nanocomposites, wound healing, excision wound, angiogenesis, vascular endothelial growth factor, TGF-β1, TNF-α, IL-10, fibroblast proliferation, collagen deposition, re-epithelialization, CD31, topical application
- MeSH terms
- Animals, Copper, Gene Expression Regulation, Male, Skin, Time Factors, Tumor Necrosis Factor-alpha, Wound Healing, Interleukin-10, Rats, Wistar, Acetic Acid, Vascular Endothelial Growth Factor A, Chitosan, Rats, Nanocomposites, Metal Nanoparticles, Transforming Growth Factor beta1
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