中国组织工程研究 ›› 2026, Vol. 30 ›› Issue (2): 395-403.doi: 10.12307/2025.893

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

脱细胞真皮基质水凝胶促进大鼠皮肤创面的愈合

刘晓红1,赵  天1,穆云萍1,冯文金2,吕存声2,张智永2,赵子建3,李芳红1   

  1. 1广东工业大学生物医药学院,广东省广州市   510006;2浙江华臻医疗器械有限公司,浙江省温州市   325000;3南方医科大学南方医院,广东省广州市   510515
  • 收稿日期:2024-08-12 接受日期:2024-10-23 出版日期:2026-01-18 发布日期:2025-06-18
  • 通讯作者: 赵子建,博士,教授,南方医科大学南方医院,广东省广州市 510515 李芳红,博士,教授,广东工业大学生物医药学院,广东省广州市 510006
  • 作者简介:刘晓红,女,1999年生,广东省揭阳市人,汉族,广东工业大学生物医药学院在读硕士,主要从事组织修复材料和再生医学方面的研究。
  • 基金资助:
    国家重点研发计划项目(2018YFA0800603),项目负责人:赵子建;广州市科技计划项目(2023B03J1291),项目负责人:赵子建

Acellular dermal matrix hydrogel promotes skin wound healing in rats

Liu Xiaohong1, Zhao Tian1, Mu Yunping1, Feng Wenjin2, Lyu Cunsheng2, Zhang Zhiyong2, Zhao Zijian3, Li Fanghong1#br#   

  1. 1School of Biomedical and Pharmaceutical Sciences, Guangdong University of Technology, Guangzhou 510006, Guangdong Province, China; 2Zhejiang Huazhen Medical Equipment Co., Ltd., Wenzhou 325000, Zhejiang Province, China; 3Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong Province, China
  • Received:2024-08-12 Accepted:2024-10-23 Online:2026-01-18 Published:2025-06-18
  • Contact: Zhao Zijian, MD, Professor, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong Province, China Li Fanghong, MD, Professor, School of Biomedical and Pharmaceutical Sciences, Guangdong University of Technology, Guangzhou 510006, Guangdong Province, China
  • About author:Liu Xiaohong, Master candidate, School of Biomedical and Pharmaceutical Sciences, Guangdong University of Technology, Guangzhou 510006, Guangdong Province, China
  • Supported by:
    National Key Research & Development Program, No. 2018YFA0800603 (to ZZJ); Guangzhou Science and Technology Program, No. 2023B03J1291 (to ZZJ)

摘要:

文题释义:
脱细胞真皮基质:通过脱细胞方法去除真皮组织中具有免疫原性的各种细胞,选择性地保留有生物活性的细胞外基质。脱细胞真皮基质具有良好的生物相容性和可降解性,是一种理想的伤口敷料,临床应用潜力巨大。
水凝胶:是一种以水为分散介质、具有三维网络结构的高分子材料,具有良好的生物相容性、药物负载和缓释特性、独特的多孔结构、渗透性和亲水性,水凝胶能够模仿天然细胞外基质并为细胞提供适宜的微环境,一直是医疗组织工程研究的热点。

背景:促进皮肤创面愈合是全球公共卫生面临的巨大挑战,为促进创面更快、更高质量愈合还需挖掘更具优势的敷料以应对这一难题。
目的:探讨脱细胞真皮基质水凝胶的止血性能以及对皮肤创面愈合的影响。
方法:①制备脱细胞真皮基质水凝胶,分析其与脱细胞真皮基质微观形貌和主要成分的差异。②使用脱细胞真皮基质水凝胶与壳聚糖水凝胶分别覆盖大鼠股动脉穿刺口,记录出血量与凝血时间。将脱细胞真皮基质水凝胶与壳聚糖水凝胶分别与大鼠抗凝血混合,检测
30 min内的凝血指数。③在18只SD大鼠背部制作直径12 mm的皮肤全层缺损模型,随机分3组处理,每组6只:模型组使用PBS清洗创面,对照组、实验组分别使用壳聚糖水凝胶、脱细胞真皮基质水凝胶覆盖创面,每天更换水凝胶敷料,连续处理14 d,观察创面愈合情况。造模后第3天,进行创面诱导型一氧化氮合酶(M1型巨噬细胞)与CD206(M2型巨噬细胞)免疫荧光染色;造模后第14天,进行创面苏木精-伊红染色、Masson染色与CD31免疫组化染色。
结果与结论:①扫描电镜下可见脱细胞真皮基质水凝胶呈多孔结构,傅里叶变换红外光谱显示其与脱细胞真皮基质的主要成分相同。②脱细胞真皮基质水凝胶与壳聚糖水凝胶均有明显的体内止血能力;体外凝血实验中,脱细胞真皮基质水凝胶的凝血指数显著高于壳聚糖水凝胶。③在大鼠皮肤全层缺损模型中,脱细胞真皮基质水凝胶与壳聚糖水凝胶均可提高创面愈合率。苏木精-伊红与Masson染色结果显示,脱细胞真皮基质水凝胶可减轻创面中心部位炎症细胞浸润,脱细胞真皮基质水凝胶与壳聚糖水凝胶均可减小瘢痕宽度、提升胶原沉积率。CD31免疫组化染色结果显示两种水凝胶均可促进创面部位血管生成。免疫荧光染色结果显示,两种水凝胶均可降低M1型巨噬细胞比例、提升M2型巨噬细胞比例,并且脱细胞真皮基质水凝胶的作用强于壳聚糖水凝胶。④结果表明,脱细胞真皮基质水凝胶具有良好的止血性能与促创面愈合能力。

https://orcid.org/0009-0006-0140-9256 (刘晓红)

 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: 创面愈合, 脱细胞真皮基质, 壳聚糖, 水凝胶, 组织修复, 止血, 工程化皮肤材料

Abstract: BACKGROUND: Promoting skin wound healing is a huge challenge facing global public health. To promote faster and higher-quality wound healing, it is necessary to explore more advantageous dressings to address this problem.
OBJECTIVE: To investigate the hemostatic properties of acellular dermal matrix hydrogel and its effect on skin wound healing. 
METHODS: (1) Acellular dermal matrix hydrogel was prepared, and the differences in microscopic morphology and main components between it and acellular dermal matrix were analyzed. (2) Acellular dermal matrix hydrogel and chitosan hydrogel were used to cover the femoral artery puncture site of rats, and the bleeding quality and coagulation time were recorded. Acellular dermal matrix hydrogel and chitosan hydrogel were mixed with rat anticoagulated blood, and the coagulation index within 30 minutes was detected. (3) A full-thickness skin defect model with a diameter of 12 mm was made on the back of 18 SD rats, and they were randomly divided into 3 groups, with 6 rats in each group: the model group used PBS to clean the wound, and the control group and the experimental group used chitosan hydrogel and acellular dermal matrix hydrogel to cover the wound, respectively. The hydrogel dressing was changed every day, and the treatment was continued for 14 days, and the wound healing was observed. On day 3 after modeling, immunofluorescence staining of inducible nitric oxide synthase (M1 macrophages) and CD206 (M2 macrophages) was performed on the wound surface. On day 14 after modeling, hematoxylin-eosin staining, Masson staining, and CD31 immunohistochemical staining were performed on the wound surface.
RESULTS AND CONCLUSION: (1) Scanning electron microscopy revealed that the acellular dermal matrix hydrogel had a porous structure, and the Fourier transform infrared spectrum showed that it had the same main components as the acellular dermal matrix. (2) Both acellular dermal matrix hydrogel and chitosan hydrogel had obvious hemostatic ability in vivo. In the in vitro coagulation experiments, the coagulation index of acellular dermal matrix hydrogel was significantly higher than that of chitosan hydrogel. (3) In the rat skin full-thickness defect model, both acellular dermal matrix hydrogel and chitosan hydrogel could improve the wound healing rate. Hematoxylin-eosin and Masson staining results showed that acellular dermal matrix hydrogel could reduce the infiltration of inflammatory cells in the center of the wound. Both acellular dermal matrix hydrogel and chitosan hydrogel could decrease scar width and increase collagen deposition rate. CD31 immunohistochemical staining results showed that both hydrogels could promote angiogenesis in the wound site. Immunofluorescence staining results showed that both hydrogels could reduce the proportion of M1 macrophages and increase the proportion of M2 macrophages, and the effect of acellular dermal matrix hydrogel was stronger than that of chitosan hydrogel. (4) The results show that the acellular dermal matrix hydrogel has good hemostatic properties and the ability to promote wound healing.


Key words: wound healing, acellular derma, matrix, chitosan, hydrogel, tissue restoration, hemostasis, engineered skin materials

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