载雷奈酸锶海藻酸钠/胶原水凝胶促进骨性关节炎骨缺损的修复  

Strontium ranelate-loaded sodium alginate/collagen hydrogel promotes bone defect repair in osteoarthritis

作　　者：苏坤阳 陈毕能 陈益樑 金少枫 Su Kunyang;Chen Bineng;Chen Yiliang;Jin Shaofeng(Department of Traditional Chinese Medicine Rehabilitation,910 Hospital of Chinese People's Liberation Army Joint Logistics Support Force(Quanzhou Strait Hospital),Quanzhou 362000,Fujian Province,China)

机构地区：[1]中国人民解放军联勤保障部队第九一〇医院(泉州市海峡医院)中医康复科,福建省泉州市362000

出　　处：《中国组织工程研究》2024年第10期1568-1574,共7页Chinese Journal of Tissue Engineering Research

摘　　要：背景:软骨退行性变和软骨下骨损伤是骨性关节炎的主要病理特征,根据这一病理特征进行局部调控将是骨性关节炎治疗的有前景改进方案。目的:设计并研究一种可注射载雷奈酸锶药物递送系统,观察其在骨性关节炎局部促进软骨修复并改善软骨下骨结构的治疗效果。方法:①体外实验:将雷奈酸锶搭载于海藻酸钠/胶原水凝胶基质中构建原位药物递送系统,表征该系统的体外缓释性能。将载雷奈酸锶海藻酸钠/胶原水凝胶(实验组)、海藻酸钠/胶原水凝胶(对照组)分别与骨髓间充质干细胞共培养,以单独培养的细胞为空白对照组,检测细胞增殖活性;在成软骨诱导分化后,分别进行番红O染色、阿利新蓝染色及RT-qPCR检测。将两种水凝胶分别与成骨细胞共培养,以单独培养的细胞为空白对照组,进行免疫荧光染色及RT-qPCR检测。②体内实验:取18只成年SD大鼠,通过内侧半月板切除的方法建立右后侧膝骨性关节炎模型,造模后1周,采用随机数字表法分3组处理:空白组不进行任何处理,对照组膝关节腔内注射海藻酸钠/胶原水凝胶,实验组右膝关节腔内注射载雷奈酸锶海藻酸钠/胶原水凝胶,每组6只。造模后第6周取材,分别进行Micro-CT扫描、苏木精-伊红染色、番红O染色及免疫荧光染色。结果与结论:①体外实验:载雷奈酸锶海藻酸钠/胶原水凝胶具有疏松多孔的微观结构,可持续释放雷奈酸锶,至21 d时累计释放量(60.89±0.58)%。骨髓间充质干细胞活死染色显示,两种水凝胶均具有良好的细胞相容性。CCK-8检测显示,载雷奈酸锶海藻酸钠/胶原水凝胶可促进骨髓间充质干细胞的增殖;番红O染色、阿利新蓝染色、免疫荧光染色及RT-qPCR检测显示,载雷奈酸锶海藻酸钠/胶原水凝胶可促进骨髓间充质干细胞的成软骨分化。免疫荧光染色及RT-qPCR检测显示,载雷奈酸锶海藻酸钠/胶原水凝胶可通过�BACKGROUND:Cartilage degeneration and subchondral bone damage are the main pathological features of osteoarthritis,and treatment based on this pathological feature will be a promising improvement for osteoarthritis.OBJECTIVE:To design and study an annotated strontium ranelate-loaded drug delivery system and to observe its therapeutic effect on promoting cartilage repair and improving subchondral bone structure in osteoarthritis.METHODS:(1)In vitro experiment:Strontium ranelate was loaded into sodium alginate/collagen hydrogel matrix to construct in situ drug delivery system,and the in vitro slow release performance of the system was characterized.Strontium ranelate-loaded sodium alginate/collagen hydrogel(experimental group)and alginate sodium/collagen hydrogel(control group)were co-cultured with bone marrow mesenchymal stem cells,respectively,and cultured cells were used as a blank control group to detect cell proliferative activity.After chondroblast-induced differentiation,saffron O staining,Alcian blue staining and RT-qPCR were performed respectively.The two hydrogels were co-cultured with osteoblasts,and the cultured cells were used as a blank control group for immunofluorescence staining and RT-qPCR.(2)In vivo experiment:A total of 18 adult SD rats were selected and the model of right posterior knee osteoarthritis was established by the method of medial meniscectomy.After 1 week,the rats were divided into three groups by the random number table method:The blank group did not receive any treatment.The control group was injected with sodium alginate/collagen hydrogel in the knee,and the experimental group was injected with strontium ranelate-loaded sodium alginate/collagen hydrogel,with 6 rats in each group.After 6 weeks,the samples were subjected to Micro-CT scanning,hematoxylin-eosin staining,saffron O-solid green staining and immunofluorescence staining.RESULTS AND CONCLUSION:(1)In vitro experiment:Strontium ranelate-loaded sodium alginate/collagen hydrogel had porous microstructure and sustainable release

关 键 词：骨关节炎 药物递送系统 海藻酸钠/胶原水凝胶 雷奈酸锶 软骨下骨 软骨修复 

分 类 号：R459.9[医药卫生—治疗学] R313[医药卫生—临床医学] R965