Enhanced Skin Wound Healing Through Chemically Modified Messenger RNA Encoding Epidermal Growth Factor ( EGF )

作者：Haiyang Hu, Qianglong Sheng, Fan Yang, Xinyi Wu, Youlai Zhang, Shuling Wu, Yihu Liu, Ningyan Hu, Chenhong Fu, Jialin Leong, Rufei Deng, Zhenyu Jiang, Jiaxin Chen, Zhen‐Xing Wang, Chun‐Yuan Chen, Fei Chen, Yixuan Luo, Yuanlin Zeng, Yu Yin, Hui Xie, Gang Wang, Lijin Zou · 发表于：International Wound Journal · 年份：2025 · DOI：10.1111/iwj.70143 · 被引用次数：7 · 研究领域：Wound Healing and Treatments、Silk-based biomaterials and applications、RNA Interference and Gene Delivery

Efficient wound healing remains a formidable medical challenge in clinical practice, due to the prevalence of skin defects arising from diverse etiological factors. 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-life in vivo 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-saline 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% ± 1.25% and 90.37% ± 0.97%, respectively), resulting in efficient production of biologically active EGF protein. In vitro, EGF cmRNA significantly promoted HaCaT and NHDF cell cycle, proliferation and migration. In vivo, in vivo imaging system (IVIS) imaging of murine skin confirmed localised and sustained expression of Luciferase cmRNA, with signals detectable up to 11 days post-injection. Immunohistochemistry revealed protein expression in both epidermal and dermal layers as early as 1 h post-injection, peaking at 48 h, further corroborated by enzyme-link...