中国组织工程研究

中国组织工程研究 ›› 2023, Vol. 27 ›› Issue (12): 1927-1931.doi: 10.12307/2023.004

• 药物控释材料 drug delivery materials • 上一篇    下一篇

温敏性水凝胶Pluronic F127载硫化铜纳米颗粒修复大鼠感染性创面

胡金龙，全桦红，王静成，张  佩，张家乐，陈鹏涛，梁  远   

  1. 扬州大学临床医学院创伤骨科，江苏省扬州市  225001
  • 收稿日期:2021-10-11 接受日期:2021-12-01 出版日期:2023-04-28 发布日期:2022-07-30
  • 通讯作者: 梁远，博士，主治医师，扬州大学临床医学院(苏北人民医院)创伤骨科，江苏省扬州市 225001
  • 作者简介:胡金龙，男，1987年生，安徽省淮南市人，汉族，2014年扬州大学毕业，硕士，主治医师，主要从事骨科创伤及感染相关治疗及研究。
  • 基金资助:
    江苏省医学创新团队项目(CXTDB2017004)，项目名称：骨科术后瘢痕粘连的预防和综合治疗，项目负责人：王静成

Effect of copper sulfide nanoparticles loaded thermosensitive hydrogel Pluronic F127 on infected wound healing in rats

Hu Jinlong, Quan Huahong, Wang Jingcheng, Zhang Pei, Zhang Jiale, Chen Pengtao, Liang Yuan   

  1. Department of Orthopedics, Clinical Medical College of Yangzhou University, Yangzhou 225001, Jiangsu Province, China
  • Received:2021-10-11 Accepted:2021-12-01 Online:2023-04-28 Published:2022-07-30
  • Contact: Liang Yuan, MD, Attending physician, Department of Orthopedics, Clinical Medical College of Yangzhou University, Yangzhou 225001, Jiangsu Province, China
  • About author:Hu Jinlong, Master, Attending physician, Department of Orthopedics, Clinical Medical College of Yangzhou University, Yangzhou 225001, Jiangsu Province, China
  • Supported by:
    Jiangsu Provincial Medical Innovation Team Project, No. CXTDB2017004 (to WJC)

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摘要：

文题释义：
温敏性水凝胶：是研究最为深入的刺激响应性聚合物，不需要额外的有潜在细胞毒性的有机溶剂、共聚剂或凝胶引发剂，在人体温度下即可发生凝胶化，因此在皮肤替代物领域已获得广泛关注。这类水凝胶的标志性特征是临界溶解温度，在临界溶解温度以下聚合物可溶，在临界溶解温度以上聚合物则变为疏水和不溶，导致凝胶形成，这是将温敏性水凝胶应用于创面的关键。
Pluronic：由聚(环氧乙烷)-聚(环氧丙烷)-聚(环氧乙烷)(PEO-PPO-PEO)组成，是一种广泛应用的合成聚合物。Pluronic胶束被认为是一种新型纳米药物，可以增加溶解度和改善循环时间，并在目标部位释放药物。Pluronic共聚物可以自组装成球形胶束，其中环氧乙烷作为亲水性外壳、环氧丙烷作为疏水性内核。将疏水性药物包封在环氧丙烷核心中，将水不溶性化合物转移到胶束溶液的环氧丙烷核心中的过程称为“溶解”。Pluronics胶束可以显著提高疏水性药物的溶解度。

背景：硫化铜纳米颗粒具有良好的抗菌及促进创面愈合效果，但其在伤口不易存留，一定程度上限制了其应用。
目的：探讨温敏性水凝胶Pluronic F127载硫化铜纳米颗粒对大鼠感染性创面愈合的作用。 
方法：分别制备硫化铜纳米颗粒、温敏性水凝胶Pluronic F127及温敏性水凝胶Pluronic F127载硫化铜纳米颗粒。取24只雄性Wistar大鼠，建立背部金黄色葡萄球菌感染性创面模型，1 d后随机分3组，对照组创面注射PBS，水凝胶组创面覆盖温敏性水凝胶Pluronic F127，纳米颗粒组创面覆盖温敏性水凝胶Pluronic F127载硫化铜纳米颗粒，每组8只。创面处理后第3天，进行创面细菌学检测；创面处理后第14天，测量创面面积，采血检测大鼠肝肾功能，观察创面及主要脏器组织学变化。
结果与结论：①创面处理第3天，纳米颗粒组大鼠创面组织菌落数明显少于对照组、水凝胶组(P < 0.05)；②创面处理第14天，纳米颗粒组大鼠创面面积小于对照组、水凝胶组(P < 0.05)；③创面处理第14天，创面组织苏木精-伊红染色显示，纳米颗粒组可见较为致密成熟的肉芽组织，对照组及水凝胶组可见大量疏松未成熟的肉芽组织；Masson染色显示，对照组及水凝胶组可见疏松的胶原组织，纳米颗粒组可见致密的胶原组织；④3组大鼠的肝肾功能指标值比较差异无显著性意义(P > 0.05)，主要脏器心、肝、脾、肺、肾等未见明显的病理组织学改变；⑤结果表明，温敏性水凝胶Pluronic F127载硫化铜纳米颗粒可以明显抑制细菌的生长，促进感染性创面的愈合。

https://orcid.org/0000-0002-9612-7684 (胡金龙) 

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: 硫化铜纳米颗粒, 水凝胶, 抗菌, 创面愈合, 金黄色葡萄球菌, 大鼠, 感染模型

Abstract: BACKGROUND: Copper sulfide nanoparticles have good antibacterial and wound healing effects, but they are not easy to persist in wounds, which limits their application to a certain extent.
OBJECTIVE: To investigate the effect of copper sulfide nanoparticles loaded thermosensitive hydrogel Pluronic F127 on infected wound healing in rats. 
METHODS: Copper sulfide nanoparticles, thermosensitive hydrogel Pluronic F127, and copper sulfide nanoparticles loaded Pluronic F127 were prepared respectively. Twenty-four male Wistar rats were taken to establish a wound model of Staphylococcus aureus on the back. One day later, they were randomly divided into three groups (n=8). In the control group, the wounds were injected with PBS. In the hydrogel group, the wounds were covered with thermosensitive hydrogel pluronic F127. In the nanoparticle group, the wounds were covered with copper sulfide nanoparticles loaded with thermosensitive hydrogel Pluronic F127. On day 3 after wound treatment, the bacteriological test of the wound was performed. On day 14 after wound treatment, the wound area was measured; blood was collected to test the liver and kidney functions of the rats and the histological changes of the wound and main organs were observed.
RESULTS AND CONCLUSION: (1) On day 3 of wound treatment, the number of colonies in the wound tissue was significantly lower in the nanoparticle group than that of the control and hydrogel groups (P < 0.05). (2) On day 14 of wound treatment, the wound area of the rats was smaller in the nanoparticle group than that in the control and hydrogel groups (P < 0.05). (3) On  day 14 of wound treatment, hematoxylin-eosin staining of wound tissue displayed that relatively dense and mature granulation tissue was seen in the nanoparticle group, while a large number of loose and immature granulation tissues were seen in the control and hydrogel groups. Masson staining exhibited that loose collagen tissue was seen in the control and hydrogel groups, and dense collagen tissue was seen in the nanoparticle group. (4) There was no significant difference in liver and kidney function index values among the three groups (P > 0.05). No obvious histopathological changes were found in the main organs such as heart, liver, spleen, lung, and kidney. (5) Pluronic F127 hydrogel loaded copper sulfide nanoparticles could obviously inhibit the growth of bacteria and promote the healing of infectious wounds.

Key words: copper sulfide nanoparticle, hydrogel, antibacteria, wound healing, Staphylococcus aureus, rat, infection model

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