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  

Tannic acid modified interpenetrating network hydrogel promotes tissue remodeling of ruptured Achilles tendon after surgery

作　　者：张博[1] 张振 江东[1] Zhang Bo;Zhang Zhen;Jiang Dong(Department of Sports Medicine,Peking University Third Hospital,Beijing 100191,China)

机构地区：[1]北京大学第三医院运动医学科,北京市100191

出　　处：《中国组织工程研究》2025年第4期721-729,共9页Chinese Journal of Tissue Engineering Research

基　　金：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。

摘　　要：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3-10μm,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�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 3-10μm,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 Achi

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 

分 类 号：R459.9[医药卫生—治疗学] R318[医药卫生—临床医学] R686