中国组织工程研究

中国组织工程研究 ›› 2021, Vol. 25 ›› Issue (22): 3445-3449.doi: 10.3969/j.issn.2095-4344.3182

• 水凝胶材料Hydrogel materials •    下一篇

臭氧缓释水凝胶止血及促伤口愈合作用

刘  方，单争明，汤雨蕾，伍晓敏，田卫群   

  1. 武汉大学基础医学院生物医学工程系，湖北省武汉市  430071
  • 收稿日期:2020-02-13 修回日期:2020-02-24 接受日期:2020-06-29 出版日期:2021-08-08 发布日期:2021-01-19
  • 通讯作者: 田卫群，博士，硕士生导师，武汉大学基础医学院生物医学工程系，湖北省武汉市 430071
  • 作者简介:刘方，女，1984年生，河南省西华县人，汉族，武汉大学基础医学院在读硕士，主要从事生物材料与再生医学的相关研究。
  • 基金资助:
    武汉大学医学部大学生创新实验项目(MS2018006)，项目负责人：田卫群

Effects of hemostasis and promoting wound healing of ozone sustained-release hydrogel

Liu Fang, Shan Zhengming, Tang Yulei, Wu Xiaomin, Tian Weiqun   

  1. Department of Biomedical Engineering, School of Basic Medical Sciences, Wuhan University, Wuhan 430071, Hubei Province, China
  • Received:2020-02-13 Revised:2020-02-24 Accepted:2020-06-29 Online:2021-08-08 Published:2021-01-19
  • Contact: Tian Weiqun, MD, Master’s supervisor, Department of Biomedical Engineering, School of Basic Medical Sciences, Wuhan University, Wuhan 430071, Hubei Province, China
  • About author:Liu Fang, Master candidate, Department of Biomedical Engineering, School of Basic Medical Sciences, Wuhan University, Wuhan 430071, Hubei Province, China
  • Supported by:
    Innovation Experiment Program for Medical College Students of Wuhan University, No. MS2018006 (to TWQ)

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摘要：

文题释义：
臭氧半衰期：为臭氧含量衰减到初始含量一半时所需要的时间。半衰期越久则臭氧稳定性越好。根据公式 lnc=-(ln2)t/t1/2+lnC0 作lnc-t一次函数图，可以求出半衰期t1/2=-(ln2)/k，其中c为臭氧浓度，t为时间，C0为初始臭氧浓度，k为直线斜率，t1/2为半衰期。目前认为臭氧半衰期与其溶解的介质有一定关系，通过计算臭氧在介质中的半衰期可以判断臭氧在该介质中的稳定性。
水凝胶：是一种具有三维网络结构的高分子体系，具有多孔结构、较好的生物相容性和吸水性，可以均匀、连续地释放其运载的物质。此次实验中水凝胶主要作用为可以将负载在其中的臭氧进行缓释，延长臭氧作用时间，帮助稳定臭氧。

背景：臭氧具有良好的抑菌效果及止血促凝效果，但因稳定性差、极易分解，限制了其应用与推广。
目的：制备臭氧缓释水凝胶，评估其稳定性及止血与促进伤口愈合作用。
方法：①以卡波姆为基质，通过控制臭氧通入时间分别制备含臭氧浓度为(3.4±0.2)×10-6，(2.3±1.8)×10-6，(7.20±0.5)×10-6，(7.0±3.0)×10-6，(16.4±1.2)×10-6，(15.0±5.0)×10-6的臭氧缓释水凝胶，检测臭氧缓释水凝胶中臭氧的稳定性；②取15只SD大鼠制作肝脏出血模型，随机分5组处理：空白对照组使用普通清洁纱布止血；阳性对照组使用Celox止血粉止血；低、中、高浓度臭氧凝胶组分别采用含臭氧浓度(3.4±0.2)×10-6，(7.20±0.5)×10-6，(16.4±1.2)×10-6的臭氧缓释水凝胶覆盖创面，记录止血时间；③取15只SD大鼠制作背部皮肤伤口模型，随机分5组处理：空白对照组不作处理；阳性对照组涂抹京万红软膏；低、中、高浓度臭氧凝胶组分别覆盖含臭氧浓度(2.3±1.8)×10-6，(7.0±3.0)×10-6，(15.0±5.0)×10-6的臭氧缓释水凝胶，14 d内观察伤口愈合。实验项目经武汉大学动物实验伦理委员会批准，批准号：2019010019。
结果与结论：①臭氧在水凝胶中具有较好的稳定性，该稳定性可维持2周左右；②在肝脏止血实验中，与空白对照组相比，中、高浓度的臭氧缓释水凝胶与止血粉均可缩短止血时间(P < 0.01)，并且高浓度臭氧缓释水凝胶的止血时间短于止血粉(P < 0.05)；③在皮肤伤口愈合实验中，与空白对照组相比，中、高浓度的臭氧缓释水凝胶在第4天可提高伤口愈合率(P < 0.05，P < 0.01)；至14 d时，5组间伤口愈合率比较差异无显著性意义；④结果表明，臭氧缓释水凝胶具有较好的稳定性、促止血及伤口愈合功效。

关键词: 材料, 臭氧, 水凝胶, 缓释, 稳定性, 止血, 伤口愈合

Abstract: BACKGROUND: Ozone has good bacteriostatic and hemostatic effects, but its poor stability and easy decomposition limit its application and promotion.
OBJECTIVE: To prepare ozone sustained-release hydrogel, and to evaluate its stability and hemostasis and promoting effect on wound healing.
METHODS: (1) With carbomer as the substrate, the ozone sustained-release hydrogels with ozone concentrations of (3.4±0.2)×10-6, (2.3±1.8)×10-6, (7.20±0.5)×10-6, (7.0 ±3.0)×10-6, (16.4±1.2)×10-6, and (15.0±5.0)×10-6 were prepared by controlling the ozone penetration time, and the stability of ozone in the ozone sustained-release hydrogel was tested. (2) A total of 15 Sprague-Dawley rats were used to make liver hemorrhage models. They were randomly divided into five groups: the blank control group used ordinary clean gauze to stop bleeding; the positive control group used Celox hemostatic powder to stop bleeding; the low-, medium- and high-concentration ozone gel groups were covered with ozone sustained-release hydrogel containing ozone concentrations of (3.4±0.2)×10-6, (7.20±0.5)×10-6, and (16.4±1.2)×10-6, and the time of hemostasis was recorded. (3) A total of 15 Sprague-Dawley rats were used to make a model of the back skin wound. They were randomly divided into five groups: the blank control group was not treated; the positive control group was coated with Beijing Wanhong ointment; the low-, medium- and high-concentration ozone gel groups were covered with the ozone sustained-release hydrogel containing ozone concentrations of (2.3±1.8)×10-6, (7.0±3.0)×10-6, and (15.0±5.0)×10-6, and wound healing was observed within 14 days. The experimental project was approved by the animal experimental ethics committee of Wuhan University (approval No. 2019010019). 
RESULTS AND CONCLUSION: (1) Ozone had good stability in hydrogels, which could last for about 2 weeks. (2) In the liver hemostasis experiment, compared with the blank control group, the medium- and high-concentration ozone sustained-release hydrogel and hemostatic powder could shorten the hemostatic time (P < 0.01), and the hemostatic time of the high-concentration ozone sustained-release hydrogel was shorter than that of hemostatic powder (P < 0.05). (3) In the skin wound experiment, compared with the blank control group, medium- and high-concentration ozone sustained-release hydrogel could improve the wound healing rate at 4 days (P < 0.05, P < 0.01); at 14 days, there was no significant difference in wound healing rate among five groups. (4) Ozone sustained-release hydrogel has good stability, can promote hemostasis and wound healing.

Key words: materials, ozone, hydrogel, sustained-release, stability,  hemostasis, wound healing

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