Tu Jin, Xu Luhua, Guo Yuqin, Zhang Minzhi, Gan Miao, Bao Xiuzhen, Yang Rongfeng, Liu Hanjiao, Lin Fengxia
Department of Urology, Shenzhen Hospital of Integrated Traditional Chinese and Western Medicine , Shenzhen, 518104, Guangdong, China.
Department of Cardiovascular, Shenzhen Bao'an Traditional Chinese Medicine Hospital, Guangzhou University of Chinese Medicine, Shenzhen, 518100, Guangdong, China.
Bioresour Bioprocess. 2025 Jul 12;12(1):74. doi: 10.1186/s40643-025-00915-3.
Skin wound healing is a multifaceted biological process involving dynamic interactions among various cells and signaling molecules. Angiogenesis is a key component of this repair process. Dendrobium officinale, a traditional medicinal plant, has shown therapeutic promise, particularly through its bioactive nanovesicles. This study investigates the therapeutic potential of Dendrobium officinale-derived nanovesicles (DDNVs) in regulating angiogenesis, inflammation, and tissue repair, to promote enhanced skin wound healing. A full-thickness mouse skin wound model was used to evaluate the in vivo effects of DDNVs on wound closure, angiogenesis, and collagen remodeling. Histological staining (H&E and Masson's trichrome) and CD31 immunofluorescence were performed. In vitro, DDNVs were tested on Human umbilical vein endothelial cells(HUVECs) and Human keratinocyte cells (HaCaT) cells to assess cell proliferation, migration, and angiogenesis. Confocal microscopy was used to track cellular uptake. Activation of the Akt/eNOS pathway and expression of key genes related to inflammation and matrix remodeling were evaluated by Western blotting and qPCR. DDNVs significantly accelerated wound healing and promoted angiogenesis in vivo, as evidenced by enhanced CD31 expression and collagen remodeling. In vitro, DDNVs entered cells efficiently and stimulated HUVEC and HaCaT proliferation and migration. This was accompanied by activation of the Akt/eNOS signaling pathway, increased expression of eNOS and VEGFR-2, upregulation of extracellular matrix(ECM) components (Vimentin, Fibronectin, COL1A1), and suppression of inflammatory markers such as ICAM-1 and IL-1β. DDNVs exhibit strong potential to enhance skin wound healing by promoting angiogenesis, improving tissue repair, and modulating inflammation. These findings support the clinical development of DDNVs as a novel, plant-derived nanotherapeutic for chronic wound treatment and skin regeneration.
皮肤伤口愈合是一个多方面的生物学过程，涉及各种细胞和信号分子之间的动态相互作用。血管生成是这个修复过程的关键组成部分。铁皮石斛，一种传统药用植物，已显示出治疗潜力，特别是通过其生物活性纳米囊泡。本研究调查了铁皮石斛衍生的纳米囊泡（DDNVs）在调节血管生成、炎症和组织修复以促进皮肤伤口愈合增强方面的治疗潜力。使用全层小鼠皮肤伤口模型评估DDNVs对伤口闭合、血管生成和胶原重塑的体内作用。进行了组织学染色（苏木精和伊红染色以及马松三色染色）和CD31免疫荧光检测。在体外，对人脐静脉内皮细胞（HUVECs）和人角质形成细胞（HaCaT）进行DDNVs测试，以评估细胞增殖、迁移和血管生成。使用共聚焦显微镜追踪细胞摄取。通过蛋白质印迹和定量聚合酶链反应评估Akt/eNOS途径的激活以及与炎症和基质重塑相关的关键基因的表达。DDNVs在体内显著加速伤口愈合并促进血管生成，CD31表达增强和胶原重塑证明了这一点。在体外，DDNVs有效进入细胞并刺激HUVEC和HaCaT增殖和迁移。这伴随着Akt/eNOS信号通路的激活、eNOS和VEGFR - 2表达的增加、细胞外基质（ECM）成分（波形蛋白、纤连蛋白、COL1A1）的上调以及炎症标志物如ICAM - 1和IL - 1β的抑制。DDNVs通过促进血管生成、改善组织修复和调节炎症表现出增强皮肤伤口愈合的强大潜力。这些发现支持将DDNVs作为一种新型的、植物来源的纳米疗法用于慢性伤口治疗和皮肤再生的临床开发。
