中国组织工程研究 ›› 2020, Vol. 24 ›› Issue (16): 2526-2530.doi: 10.3969/j.issn.2095-4344.2244

• 组织工程口腔材料 tissue-engineered oral materials • 上一篇    下一篇

α-氰基丙烯酸正丁酯医用黏合剂修复大鼠口腔黏膜创口

胡开维1,聂  玲1,张  赫2,李雨舟2,3,4,杨  生2,3,4   

  1. 1重庆医科大学口腔医学院,重庆市  401147;2重庆医科大学附属口腔医院,重庆市  401147;3口腔疾病与生物医学重庆市重点实验室,重庆市  401147;4重庆市高校市级口腔生物医学工程重点实验室,重庆市 401147
  • 收稿日期:2019-03-18 修回日期:2019-03-28 接受日期:2019-09-02 出版日期:2020-06-08 发布日期:2020-03-25
  • 通讯作者: 杨生,博士,副主任医师,副教授,重庆医科大学附属口腔医院,重庆市 401147;口腔疾病与生物医学重庆市重点实验室,重庆市 401147;重庆市高校市级口腔生物医学工程重点实验室,重庆市 401147
  • 作者简介:胡开维,女,1993年生,四川省安岳县人,汉族,重庆医科大学在读硕士,医师,主要从事口腔黏膜组织再生及生物材料的相关研究。 共同第一作者:聂玲,女,1993年生,四川省广安市人,汉族,重庆医科大学在读硕士,医师,主要从事口腔拔牙位点保存及生物材料的相关研究。
  • 基金资助:
    国家自然科学基金(81900854)

Application of α-n-butyl 2-cyanoacrylate medical adhesive for repair of oral mucosal wound of rats

Hu Kaiwei1, Nie Ling1, Zhang He2, Li Yuzhou2, 3, 4, Yang Sheng2, 3, 4   

  1. 1College of Stomatology, Chongqing Medical University, Chongqing 401147, China; 2Stomatological Hospital of Chongqing Medical University, Chongqing 401147, China; 3Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, Chongqing 401147, China; 4Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing 401147, China
  • Received:2019-03-18 Revised:2019-03-28 Accepted:2019-09-02 Online:2020-06-08 Published:2020-03-25
  • Contact: Yang Sheng, MD, Associate chief physician, Associate professor, Stomatological Hospital of Chongqing Medical University, Chongqing 401147, China; Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, Chongqing 401147, China; Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing 401147, China
  • About author:Hu Kaiwei, Master candidate, Physician, College of Stomatology, Chongqing Medical University, Chongqing 401147, China Nie Ling, Master candidate, Physician, College of Stomatology, Chongqing Medical University, Chongqing 401147, China
  • Supported by:
    the National Natural Science Foundation of China, No. 81900854

摘要:

文题释义:

α-氰基丙烯酸正丁酯医用黏合剂:俗称504医用胶,是美国 FDA和欧洲各国批准用于人体组织内的唯一医用胶产品,具有良好的生物相容性、生物降解性、抗菌性,在室温下能快速黏合机体组织,目前作为组织黏接剂已被应用于整形美容外科、儿科手术、眼科外伤的简单、快速修补等领域。

α-氰基丙烯酸酯正丁酯黏合剂黏合切口的作用原理:该类黏合剂的α-位碳原子上含有极强吸电性的基团如-CN和-COOR,产生诱导效应,使β-位的碳原子有很强的吸电性,在遇到黏膜表面水分或者血液时能产生瞬间聚合反应,固化成膜,同时形成多极性中心,此膜通过电镜观察为直径2.0-3.0 μm的网状结构,与创面组织镶嵌,其结合力大于黏膜的张力,使创面保持对合。 

背景:α-氰基丙烯酸正丁酯医用黏合剂(504医用胶)具有良好的生物相容性、抗菌性等,是一种简单有效的粘接剂,但其在口腔领域手术切口闭合中的应用少有报道。

目的:探讨α-氰基丙烯酸正丁酯医用黏合剂在大鼠口腔黏膜创口愈合中的应用效果。

方法:取15只雌性SD大鼠(重庆医科大学实验动物中心提供),建立口腔黏膜切开创口模型,分3组:自然愈合组不做任何处理,缝线组采用可吸收性外科缝线间断缝合1针闭合创口,504黏合组采用α-氰基丙烯酸正丁酯医用黏合剂封闭创口,术后7 d进行创口大体与组织学观察。取20只雌性SD大鼠,建立口腔黏膜      1 cm×1 cm的正方形缺损模型,分2组:自然愈合组不做任何处理,504封闭组采用α-氰基丙烯酸正丁酯医用黏合剂涂布缺损区,术后10 d进行缺损部位大体与组织学观察。实验方案经重庆医科大学实验动物伦理委员会批准。

结果与结论:①口腔黏膜切开创口模型:大体观察显示3组创口愈合良好,未见红肿流脓等炎性反应;组织学观察显示,缝线组创缘上皮完整、连续,上皮钉突短而平,固有层成纤维细胞增多,缝线轨迹区可见大量炎性细胞浸润;自然愈合组、504黏合组黏膜上皮愈合完好,上皮钉突细而长,固有层成纤维细胞增殖活跃,胶原纤维数量多,504黏合组纤维排列较针缝组更为紧密有序;②口腔黏膜缺损模型:大体观察显示,自然愈合组创口愈合不全,未见肿胀、坏死溃烂等感染情况,504封闭组创面基本愈合;组织学观察显示,自然愈合组黏膜缺损明显,上皮层与固有层连接不紧密,可见坏死组织、少量成纤维细胞及大量炎性细胞浸润;504封闭组黏膜缺损创缘长度显著减小,固有层可见成纤维细胞增殖、血管再生,纤维排列一致有序;③结果表明,α-氰基丙烯酸正丁酯医用黏合剂的异物反应小,可促进黏膜组织再生,为封闭口腔黏膜创口的一种潜在方法。

ORCID: 0000-0002-5986-5231(胡开维)

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: α-氰基丙烯酸正丁酯医用黏合剂, 缝线, 口腔黏膜, 创口, 软组织再生, 组织工程, 生物相容性

Abstract:

BACKGROUND: α-n-Butyl cyanoacrylate medical adhesive (504 medical adhesive) has good biocompatibility and anti-bacterial properties. It is a simple and effective medical adhesive. Little is reported on the application of α-n-butyl cyanoacrylate medical adhesive in surgical incision closure in the field of oral cavity.

OBJECTIVE: To investigate the effect of α-n-butyl cyanoacrylate medical adhesive on oral mucosal wounds healing.

METHODS: Fifteen female SD rat (Laboratory Animal Center of Chongqing Medical University, China) models of oral mucosal incisions were established and then divided into a natural healing group (without any treatment), silk suture group (interrupted stitches with absorbable surgical suture), and 504 medical adhesive group (wound closure with α-n-butyl cyanoacrylate medical adhesive) group. At 7 days after surgery, gross and histological observation was performed. Twenty female SD rats were established into models of 1 cm × 1 cm oral mucosa defect and then divided into two groups: a natural healing group (without any treatment) and a 504 closure group (covering the wound defect with α-n-butyl cyanoacrylate medical adhesive). At 10 days after surgery, gross and histological observation of defect area was performed. This study was approved by the Animal Ethics Committee of Chongqing Medical University, China.

RESULTS AND CONCLUSION: Oral mucosal incision wound model: gross observation showed that the wounds in the three groups healed well, and no inflammatory reaction such as swelling and pus was found. Histological observation showed that the epithelium of the silk suture group was complete and continuous, the nail process of the epithelium was short and flat, the number of fibroblasts in the lamina propria increased, and a large number of inflammatory cells infiltrated in the suture track area. In the natural healing and 504 closure groups, the mucosal epithelium healed well, the nail process of the epithelium was thin and long, the fibroblasts in the lamina propria proliferated actively, and there were many collagen fibers. The fibers in the 504 closure group were arranged more closely and orderly than those in the silk suture group. Oral mucosa defect model: Gross observation showed that the wound in the natural healing group did not heal completely, and there was no infection such as swelling, necrosis, and ulceration. In the 504 closure group, wound surface basically healed. Histological observation revealed that in the natural healing group, mucosal defect was obvious, the epithelial layer was not closely connected with the lamina propria, necrotic tissue, a small amount of fibroblasts and a large number of inflammatory cells were observed. In the 504 closure group, the length of margin of mucosal defect was significantly reduced, fibroblast proliferation and vascular regeneration could be observed in the lamina propria, and fibers were orderly arranged. These results suggest that α-n-butyl cyanoacrylate medical adhesive has little foreign body reaction and can promote the regeneration of mucosal tissue, providing a potential method to close oral mucosal wound. 

Key words: α-n-butylcyanoacrylate medical adhesive, suture, oral mucosa, wound, soft tissue regeneration, tissue engineering, biocompatibility

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