软骨下钻孔联合软骨源性形态发生蛋白缓释系统修复膝关节软骨缺损

摘要

背景：有研究表明软骨源性形态发生蛋白等因子在诱导细胞分化、促进软骨修复过程中起到重要调节作用；软骨下钻孔治疗软骨缺损在临床已广为应用，但其与软骨源性形态发生蛋白等因子联合应用的相关研究至今少有报道。　　目的：将软骨下钻孔技术与关节内注射透明质酸/软骨源性形态发生蛋白1缓释载药微球(hyaluronic acid-coated cartilage-derived morphogenetic protein-1，HA/CDMP-1)相结合，观察其对软骨缺损修复的效果，并通过与单纯钻孔组及HA/CDMP-1微球组治疗结果比较，观察两者有无协同效应。　　方法：用透明质酸包被软骨源性形态发生蛋白制备缓释微球冻干保存，制备兔实验膝关节全层关节软骨缺损模型，随后将兔随机分为模型组、钻孔组、HA/CDMP-1微球组和钻孔联合HA/CDMP-1微球组，分别采用生理盐水关节腔注射，软骨缺损区钻孔，HA/CDMP-1微球关节腔注射，软骨下钻孔并HA/CDMP-1微球注射。结果与结论：建模后8，12，16周，组织学观察结果提示，钻孔联合HA/CDMP-1微球组软骨缺损区修复组织覆盖面积明显高于其他3组(P <0.05)；甲苯胺蓝染色和荧光定量PCR检测显示，钻孔联合HA/CDMP-1微球组修复的软骨组织中蛋白多糖和Ⅱ型胶原mRNA的表达明显高于其他3组(P<0.01或P<0.05)。结果证实，软骨下钻孔与关节腔内注射 HA/CDMP-1联合应用修复兔膝关节软骨缺损近期疗效满意，提示两者可能发生协同作用。%BACKGROUND:Cartilage-derived morphogenetic proteins have an important regulatory role in inducing celldifferentiation and promoting cartilage repair. Subchondral dril ing for treating cartilage defects in clinical practice has been widely used, but the related study on combined application of the cartilage-derived morphogenetic protein-1 (CDMP-1) and other factors is less. OBJECTIVE:To combine the subchondral dril ing technology with hyaluronic acid-coated CDMP-1 (HA/CDMP-1) microspheres for observation of their effects on the repair of cartilage defects, and meanwhile to compare the therapeutic effects among combination group, subchondral dril ing group and HA/CDMP-1 group as wel as to observe whether there is a synergistic effect. METHODS:HA/CDMP-1 microspheres were prepared and cryopreserved. Ful-thickness articular cartilage defect models were prepared in rabbits, and then the model rabbits were divided into model group (intra-articular injection of normal saline), subchondral dril ing group (subchondral dril ing), HA/CDMP-1 group (intra-articular injection of HA/CDMP-1), combination group (subchondral dril ing+intra-articular injection of HA/CDMP-1). RESULTS AND CONCLUSION:At 8, 12, 16 weeks after modeling, histological observations suggested that the coverage area of repair tissue was higher in the combination group than the other groups (P<0.05). Toluidine blue staining and quantitative PCR showed that the mRNA expression of proteoglycan and type II col agen was also significantly higher than in the combination group than the other groups (P<0.01 or P<0.05). These findings indicate that the intra-articular injection of HA/CDMP-1 combined with subchondral dril ing can promote the repair of articular cartilage damage effectively, suggesting a possible synergy between them.