中国组织工程研究 ›› 2025, Vol. 29 ›› Issue (4): 721-729.doi: 10.12307/2025.251

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

单宁酸改性互穿网络水凝胶促进断裂跟腱术后的组织重塑

张  博,张  振,江  东   

  1. 北京大学第三医院运动医学科,北京市  100191
  • 收稿日期:2023-12-05 接受日期:2024-01-20 出版日期:2025-02-08 发布日期:2024-05-30
  • 通讯作者: 江东,博士,教授,主任医师,博士生导师,北京大学第三医院运动医学科,北京市 100191
  • 作者简介:张博,男,1998年生,黑龙江省牡丹江市人,汉族,北京大学在读博士,主要从事运动损伤相关的组织工程研究。
  • 基金资助:
    国家自然科学基金面上项目(82072428),项目负责人:江东;北京大学国家战略合作基金项目(2022ZLHB002),项目负责人:江东

Tannic acid modified interpenetrating network hydrogel promotes tissue remodeling of ruptured Achilles tendon after surgery#br#
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Zhang Bo, Zhang Zhen, Jiang Dong   

  1. Department of Sports Medicine, Peking University Third Hospital, Beijing 100191, China
  • Received:2023-12-05 Accepted:2024-01-20 Online:2025-02-08 Published:2024-05-30
  • Contact: Jiang Dong, MD, Professor, Chief physician, Doctoral supervisor, Department of Sports Medicine, Peking University Third Hospital, Beijing 100191, China
  • About author:Zhang Bo, Doctoral candidate, Department of Sports Medicine, Peking University Third Hospital, Beijing 100191, China
  • Supported by:
    National Natural Science Foundation of China, No. 82072428 (to JD); National Strategic Cooperation Foundation of Peking University, No. 2022ZLHB002 (to JD)

摘要:

文题释义:
单宁酸:是一种天然多酚类有机化合物,可通过氢键、配位和静电等方式与多种有机物和无机物形成相互作用,因而作为黏合剂和交联剂被应用于新型生物材料的开发。单宁酸还具有抗炎、抗菌、抗氧化及抗癌等多种生物学作用,目前作为生物活性成分已被用于皮肤、血管、骨骼及肿瘤等多种疾病治疗研究,是组织工程领域最具前景的化合物之一。
互穿网络水凝胶:是由2个或多个相互独立的聚合物网络交缠互锁形成的特殊类型水凝胶。相比于传统的单一网络水凝胶,互穿网络水凝胶具备超强的力学性能、刺激响应能力以及接近于天然细胞微环境的仿生性质,目前已被用于组织工程、药物输送、体外疾病模型及生物增材制造等多个领域。
背景:跟腱断裂术后的再生与重塑是临床治疗的难点,组织工程水凝胶材料为促进跟腱修复提供了可能。
目的:探究单宁酸改性互穿网络水凝胶对大鼠断裂跟腱组织再生与重塑的作用。
方法:①通过蓝光照射及CaSO4溶液浸泡交联制备单宁酸改性互穿网络水凝胶,表征水凝胶的微观形貌、力学性能、黏附性能、体外释药性能与生物相容性。②取30只SD大鼠,采用随机数字表法分为假手术组、手术组与水凝胶组,每组10只,后2组建立右后肢跟腱断裂模型,手术组采用改良Kessler法将断裂跟腱重新缝合,水凝胶组采用相同术式缝合断裂跟腱后将单宁酸改性互穿网络水凝胶贴片完全缠绕包裹于断端接合处。术后4周,对断裂跟腱进行影像学检查、组织学评价、生物力学测试及炎症因子水平检测。
结果与结论:①扫描电镜下可见单宁酸改性互穿网络水凝胶呈多孔微观结构,孔径为3-10 μm,并且水凝胶具备良好的体外释药性能、黏附强度与拉伸强度;CCK-8检测与活/死染色显示,该水凝胶对大鼠骨髓间充质干细胞增殖活性无明显影响,具备良好的生物相容性。②MRI成像显示,与手术组比较,水凝胶组大鼠跟腱呈均一低信号,跟腱前后径厚度减小,与周围组织分界更为明确,表现更接近假手术组。苏木精-伊红与Masson染色显示,手术组大鼠跟腱纤维排列松散混乱,细胞密度增加且排布杂乱,伴有明显炎性细胞浸润,部分区域出现腱内骨化;水凝胶组大鼠跟腱纤维排列有序,细胞密度降低且排布规整,炎性细胞浸润明显减少。手术组大鼠跟腱的拉伸强度低于假手术组(P < 0.05),水凝胶组大鼠跟腱的拉伸强度高于手术组(P < 0.05)。与假手术组比较,手术组大鼠跟腱中白细胞介素1β、白细胞介素6及肿瘤坏死因子α质量浓度及mRNA表达升高(P < 0.05);与手术组比较,水凝胶组3种炎症因子水平及mRNA表达降低。③结果表明,单宁酸改性互穿网络水凝胶可显著抑制局部炎症反应、促进断裂跟腱组织重塑。

https://orcid.org/0009-0004-8586-1260(张博)

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: 单宁酸, 水凝胶, 互穿网络, 跟腱断裂, 组织重塑, 组织再生

Abstract: BACKGROUND: The regeneration and remodeling of Achilles tendon rupture after surgery are difficulties in clinical treatment. Tissue engineering hydrogels afford the possibility on the healing of postoperative Achilles tendon.
OBJECTIVE: To investigate the effect of tannic acid modified interpenetrating network hydrogel on tissue regeneration and remodeling of ruptured Achilles tendon in rats.
METHODS: (1) The interpenetrating network hydrogel was prepared under the blue light and the immersion of CaSO4 solution. The micromorphology, mechanical properties, adhesion properties, in vitro drug release properties, and biocompatibility of hydrogels were characterized. (2) Thirty Sprague-Dawley rats were randomly divided into sham operation group, operation group, and hydrogel group, with 10 rats in each group. The animal model of Achilles tendon rupture was established in the latter two groups. In the operation group, the ruptured Achilles tendon was sutured using the modified Kessler method. In the hydrogel group, the ruptured Achilles tendon was repaired by the same method, and the tannic acid modified interpenetrating network hydrogel patch was completely wrapped around the joint of the broken end. Four weeks after the operation, imaging examination, histological evaluation, biomechanical test, and the level test of inflammatory factors were performed. 
RESULTS AND CONCLUSION: (1) Scanning electron microscope showed that tannic acid modified interpenetrating network hydrogels had porous microstructure with pore size of 3-10 μm, and the hydrogels had good in vitro drug release properties, adhesion strength and tensile strength. CCK-8 assay and live/dead staining showed that the hydrogel had no significant effect on the proliferation activity of rat bone marrow mesenchymal stem cells, and had good biocompatibility. (2) MRI imaging showed that compared with the operation group, the Achilles tendon in the hydrogel group showed uniform low signal, the thickness of the anteroposterior diameter of the Achilles tendon was reduced, and the boundary between the Achilles tendon and the surrounding tissue was more clear, and the performance was more similar to that of the sham operation group. Hematoxylin-eosin staining and Masson staining showed that the tendon fibers in the operation group were arranged in a loose and chaotic manner, with increased cell density and disordered arrangement, accompanied by obvious inflammatory cell infiltration, and intratendinous ossification appeared in some areas. In the hydrogel group, the tendon fibers were arranged in an orderly manner; the cell density was reduced and arranged orderly; the inflammatory cell infiltration was significantly reduced. The tensile strength of Achilles tendon in the operation group was lower than that in the sham operation group (P < 0.05). The tensile strength of Achilles tendon in the hydrogel group was higher than that in the operation group (P < 0.05). Compared with sham operation group, the mass concentration and mRNA expression of interleukin-1β, interleukin-6, and tumor necrosis factor α in Achilles tendon of rats were increased in the operation group (P < 0.05). Compared with the operation group, the level and mRNA expression of three inflammatory factors were decreased in the hydrogel group. (3) It is concluded that tannic acid modified interpenetrating network hydrogel can inhibit the local inflammatory response and promote the tendon remodeling.

Key words: tannic acid, hydrogel, interpenetrating network, Achilles tendon rupture, tissue remodeling, tissue regeneration

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