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It is indisputable that epidermal growth factor (EGF) plays a pivotal role in wound repair. However, its clinical application through recombinant proteins encounters challenges, including a short half\u2010life in\u00a0vivo and high production costs. Addressing these limitations, recent advancements in chemically modified mRNA (cmRNA) technologies offer a promising alternative. This study explores the utilisation of cmRNA in a biocompatible citrate\u2010saline formulation to encode EGF for therapeutic purposes, capitalising on the advantages of cmRNA's inherent stability and the formulation's compatibility with biological systems. CmRNA demonstrated high transfection efficiency in human immortalised keratinocyte (HaCaT) and normal human dermal fibroblasts (NHDF) cells (93.97%\u2009\u00b1\u20091.25% and 90.37%\u2009\u00b1\u20090.97%, respectively), resulting in efficient production of biologically active EGF protein. In\u00a0vitro, EGF cmRNA significantly promoted HaCaT and NHDF cell cycle, proliferation and migration. In\u00a0vivo, in\u00a0vivo imaging system (IVIS) imaging of murine skin confirmed localised and sustained expression of Luciferase cmRNA, with signals detectable up to 11\u2009days post\u2010injection. Immunohistochemistry revealed protein expression in both epidermal and dermal layers as early as 1\u2009h post\u2010injection, peaking at 48\u2009h, further corroborated by enzyme\u2010linked immunosorbent assay (ELISA). In a full\u2010thickness skin defect mouse model, EGF cmRNA significantly accelerated wound healing, with superior re\u2010epithelialisation observed compared to controls by Day 6. Mitogen\u2010activated protein kinase (MEK)\/Extracellular signal\u2010regulated kinase (ERK) and Ki67 mRNA expression levels were markedly increased, both in\u00a0vitro and in\u00a0vivo. By Day 14, histological and immunohistochemical analyses revealed that EGF cmRNA outperformed recombinant human EGF (rhEGF), as indicated by enhanced formation of hair follicles and cutaneous glands, better\u2010organised collagen fibres, and a reduced collagen Type I\/III ratio. No adverse effects were observed in major organs, confirming cmRNA's biosafety. These results highlight the therapeutic potential of EGF\u2010encoding cmRNA as an effective and safe alternative for enhancing wound healing.<\/jats:p>","DOI":"10.1111\/iwj.70143","type":"journal-article","created":{"date-parts":[[2025,5,5]],"date-time":"2025-05-05T00:23:58Z","timestamp":1746404638000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Enhanced Skin Wound Healing Through Chemically Modified Messenger\n                    <scp>RNA<\/scp>\n                    Encoding Epidermal Growth Factor (\n                    <scp>EGF<\/scp>\n                    )"],"prefix":"10.1111","volume":"22","author":[{"given":"Haiyang","family":"Hu","sequence":"first","affiliation":[{"name":"Jiangxi Provincial Key Laboratory of Trauma, Burn and Pain Medicine, Medical Center of Burn Plastic and Wound Repair, The First Affiliated Hospital, Jiangxi Medical College Nanchang University  Nanchang Jiangxi 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and Wound Repair, The First Affiliated Hospital, Jiangxi Medical College Nanchang University  Nanchang Jiangxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenyu","family":"Jiang","sequence":"additional","affiliation":[{"name":"Jiangxi Provincial Key Laboratory of Trauma, Burn and Pain Medicine, Medical Center of Burn Plastic and Wound Repair, The First Affiliated Hospital, Jiangxi Medical College Nanchang University  Nanchang Jiangxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaxin","family":"Chen","sequence":"additional","affiliation":[{"name":"Jiangxi Provincial Key Laboratory of Trauma, Burn and Pain Medicine, Medical Center of Burn Plastic and Wound Repair, The First Affiliated Hospital, Jiangxi Medical College Nanchang University  Nanchang Jiangxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenxing","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, Movement 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