中国组织工程研究

中国组织工程研究 ›› 2025, Vol. 29 ›› Issue (34): 7344-7352.doi: 10.12307/2025.491

• 水凝胶材料Hydrogel materials • 上一篇    下一篇

鹿茸干细胞外泌体复合水凝胶促进烫伤皮肤的修复

赵建伟，李勋胜，吕金朋，周  珏，蒋一頔，岳志刚，孙红梅   

  1. 中国农业科学院特产研究所，吉林省长春市   130000
  • 收稿日期:2024-07-16 接受日期:2024-09-07 出版日期:2025-12-08 发布日期:2025-01-17
  • 通讯作者: 孙红梅，博士，副研究员，硕士生导师，中国农业科学院特产研究所，吉林省长春市 130000
  • 作者简介:赵建伟，女，山东省聊城市人，汉族，中国农业科学院在读硕士，主要从事鹿茸干细胞及再生医学模型方面的研究。
  • 基金资助:
    吉林省自然科学基金项目(YDZJ202401459ZYTS)，项目负责人：孙红梅；中国农业科学院科技创新工程(CAAS-ASTIP-2021-ISAPS)，项目负责人：孙红梅

Deer antler stem cell exosome composite hydrogel promotes the repair of burned skin

Zhao Jianwei, Li Xunsheng, Lyu Jinpeng, Zhou Jue, Jiang Yidi, Yue Zhigang, Sun Hongmei   

  1. Institute of Special Animal and Plant Sciences, Chinese Academy of Agricultural Sciences, Changchun 130000, Jilin Province, China
  • Received:2024-07-16 Accepted:2024-09-07 Online:2025-12-08 Published:2025-01-17
  • Contact: Sun Hongmei, PhD, Associate researcher, Master’s supervisor, Institute of Special Animal and Plant Sciences, Chinese Academy of Agricultural Sciences, Changchun 130000, Jilin Province, China
  • About author:Zhao Jianwei, Master candidate, Institute of Special Animal and Plant Sciences, Chinese Academy of Agricultural Sciences, Changchun 130000, Jilin Province, China
  • Supported by:
    Natural Science Foundation of Jilin Province, No. YDZJ202401459ZYTS (to SHM); Science and Technology Innovation Project of Chinese Academy of Agricultural Sciences, No. CAAS-ASTIP-2021-ISAPS (to SHM)

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摘要：


文题释义：

鹿茸干细胞：鹿茸周期性再生是一种基于干细胞的过程，这种干细胞被称作鹿茸干细胞，具有胚胎干细胞和间充质干细胞的双重特性，可以被诱导分化为成骨细胞、软骨细胞和脂肪细胞等多种细胞类型。
外泌体：细胞由内出芽的方式形成的一类直径为30-150 nm的微小囊泡，这些囊泡内携带的蛋白质、脂质、mRNA、microRNA等分子可以被受体细胞摄取，从而发挥生物学功能。


背景：近年来鹿茸干细胞及外泌体促进急性皮肤损伤修复的研究得到了越来越多的关注，但外泌体复合水凝胶促进烫伤修复的效果和机制仍不清楚。

目的：探究鹿茸干细胞外泌体复合水凝胶对大鼠深Ⅲ度烫伤创面愈合速度和质量的影响及作用机制。
方法：提取鹿茸干细胞外泌体和骨髓间充质干细胞外泌体并与Pluronic F-127复合制备温敏水凝胶，采用恒温恒压烫伤仪制备大鼠深Ⅲ度烫伤模型，分4组给药：鹿茸干细胞外泌体复合水凝胶组、骨髓间充质干细胞外泌体复合水凝胶组、人表皮生长因子凝胶组和空白组。观察烫伤大鼠创面皮肤的愈合情况并计算伤口愈合率；烫伤后28 d，苏木精-伊红染色观察创面愈合组织中皮肤附属结构生成情况，马松染色观察创面愈合组织胶原积累情况，免疫组化检测创面愈合组织中血管生成和炎症反应情况，qRT-PCR检测创面愈合组织中伤口愈合相关基因mRNA表达水平。

结果与结论：①鹿茸干细胞外泌体复合水凝胶能显著提高大鼠深度烫伤的愈合速度，并通过促进皮肤附属结构的再生、增加真皮厚度和促进胶原累积来提高伤口愈合质量；②鹿茸干细胞外泌体复合水凝胶组创面愈合组织中肌成纤维细胞数量显著降低，新生血管和M2巨噬细胞数量显著增加；③鹿茸干细胞外泌体复合水凝胶组创面愈合组织中转化生长因子β3和Ⅲ型胶原的mRNA水平显著高于空白组，转化生长因子β1、基质金属蛋白酶3和Ⅰ型胶原的mRNA水平显著低于空白组，与骨髓间充质干细胞外泌体复合水凝胶组和人表皮生长因子凝胶组并无显著差异。综上所述，鹿茸干细胞外泌体复合水凝胶能提高大鼠深度烫伤的愈合速度和愈合质量，这可能是通过抑制成纤维细胞生成，促进血管生成、巨噬细胞M2极化和调节胶原生成/降解基因的表达实现的。

https://orcid.org/0000-0002-4336-941X (孙红梅) 

中国组织工程研究杂志出版内容重点：生物材料；骨生物材料；口腔生物材料；纳米材料；缓释材料；材料相容性；组织工程

关键词: 鹿茸干细胞外泌体, 深度烫伤, 肌成纤维细胞, 血管生成, 巨噬细胞极化, Pluronic F-127, 温敏水凝胶, 转化生长因子, Ⅲ型胶原, 工程化外泌体

Abstract: BACKGROUND: The study of deer antler stem cells and exosomes to promote the repair of acute skin injuries has received increasing attention in recent years, but the effect and mechanism of exosomes composite hydrogel to promote the repair of burn wounds are still unclear.
OBJECTIVE: To investigate the effect of deer antler stem cell exosome composite hydrogel on the healing speed and quality of rat deep third-degree burn wound and its mechanism of action.
METHODS: Deer antler stem cell exosomes and bone marrow mesenchymal stem cell exosomes were extracted and compounded with Pluronic F-127 to prepare a temperature-sensitive hydrogel. A constant temperature and pressure burn apparatus was used to prepare a rat model of deep third-degree burn. The drug was administered to four groups: deer antler stem cell exosome composite hydrogel group, bone marrow mesenchymal stem cell exosome composite hydrogel group, human epidermal growth factor gel group, and the control group. The healing of burned rats was observed and the wound healing rate was calculated. At 28 days after burn, hematoxylin-eosin staining was used to observe the generation of skin accessory structures in the healing tissues. Masson staining was used to analyze the accumulation of collagen in the healing tissues. Immunohistochemistry was used to examine the angiogenesis and inflammatory response in the healing tissues. qRT-PCR was used to examine the expression level of mRNA of the wound healing-related genes in the healing tissues. 
RESULTS AND CONCLUSION: (1) Deer antler stem cell exosome composite hydrogel can significantly promote the healing rate of deep burn wounds in rats, and improve the quality of wound healing by promoting the regeneration of skin collateral structures, increasing the dermal thickness and enhancing the accumulation of collagen. (2) The number of myofibroblasts in the wound healing tissues of deer antler stem cell exosome composite hydrogel group was significantly reduced, and the number of neovascularization and M2 macrophages was significantly increased. (3) The mRNA levels of transforming growth factor β3 and type III collagen in the wound healing tissue of deer antler stem cell exosome composite hydrogel group were significantly higher than those of the blank group, and the mRNA levels of transforming growth factor β1, matrix metalloproteinase 3, and type I collagen were significantly lower than those of the blank group, and there was no significant difference between the bone marrow-derived mesenchymal stem cell exosome composite hydrogel group and the human epidermal growth factor gel group. In conclusion, deer antler stem cell exosome composite hydrogel can promote the healing speed and the quality of healing of deep burned wounds in rats, which may be achieved by inhibiting fibroblastogenesis, promoting angiogenesis, macrophage M2 polarization, and regulating the expression of genes for collagen production/degradation.

Key words: deer anlter stem cell-derived exosome, deep burn, myofibroblast, angiogenesis, macrophage polarization, Pluronic F-127, thermosensitive hydrogel, transforming growth factor, type III collagen, engineered exosome

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