羟基丁酸-羟基辛酸共聚体/胶原一体化骨软骨支架复合骨髓间充质干细胞修复关节骨软骨缺损

Effect of poly(hydroxybutyrate-co-hydroxyoctanoate)/collagen composite osteochondral scaffold combined with bone marrow mesenchymal stem cells in the repair of articular osteochondral defects

背景:前期实验证实,羟基丁酸-羟基辛酸共聚体/胶原一体化骨软骨支架具备适宜的孔隙结构和良好的生物亲和性。目的:研究羟基丁酸-羟基辛酸共聚体/胶原一体化骨软骨支架复合骨髓间充质干细胞对兔关节负重区骨软骨缺损修复的效果。方法:取30只成年健康新西兰大白兔,建立右侧膝关节骨软骨缺损模型,随机分3组干预,实验组软骨缺损处植入羟基丁酸-羟基辛酸共聚体/胶原一体化骨软骨支架与骨髓间充质干细胞复合物,对照组软骨缺损处植入羟基丁酸-羟基辛酸共聚体/胶原一体化骨软骨支架,空白对照组不植入任何材料。植入后4,12周,进行骨软骨缺损处Micro-CT扫描、组织学及Ⅱ型胶原免疫组织化学染色观察。结果与结论:(1)Micro-CT扫描:至植入后12周时,空白对照组骨软骨缺损未修复;对照组骨软骨缺损缺损修复明显,再生骨小梁结构较多;实验组骨软骨缺损完全修复;(2)组织学观察:植入4周时,空白对照组缺损区被无定形的组织填充,对照组软骨下骨区域开始出现骨组织的重建,实验组软骨下骨区域出现较多的骨组织重建。植入12周时,空白对照组缺损区无骨小梁结构出现,无软骨陷窝结构;对照组软骨下骨的重建不充分,软骨层的修复由纤维组织构成;实验组骨软骨缺损区修复完全,潮线出现,软骨层厚度与周围正常软骨相似,与周围正常组织完全融合;(3)Ⅱ型胶原免疫组织化学染色:植入后12周时,空白对照组Ⅱ型胶原基本上不表达,对照组Ⅱ型胶原表达较弱,实验组软骨基质Ⅱ型胶原表达多,与周围正常软骨相似,可清楚看到潮线;(4)结果表明:羟基丁酸-羟基辛酸共聚体/胶原一体化骨软骨支架复合骨髓间充质干细胞可促进关节负重区骨软骨缺损的修复。

BACKGROUND:Preliminary experiments have confirmed that poly(hydroxybutyrate-co-hydroxyoctanoate)(PHBHOx)/collagen composite osteochondral scaffold exhibits desirable pore structure and biocompatibility.OBJECTIVE:To investigate the effect of PHBHOx/collagen composite osteochondral scaffold carrying bone marrow mesenchymal stem cells in the repair of articular osteochondral defects in the weight-bearing area of rabbits.METHODS:Cone-shaped osteochondral defects were created in the femoral medial condyle of the right knee of 30 New Zealand white rabbits.Then,the rabbit models were randomized into three groups and underwent implantation of PHBHOx/collagen composite osteochondral scaffold carrying bone marrow mesenchymal stem cells in the scaffold-cell group,PH巳HOx/collagen composite osteochondral scaffold in the scaffold group and no intervention in the control group.At 4 and 12 weeks after surgery,animals were sacrificed for gross,Micro-CT,histological and immunohistochemical collagen II observations.RESULTS AND CONCLUSION:At 12 weeks after surgery,Micro-CT scanning results suggested that osteochondral defects were not repaired in the control group,repaired incompletely in the scaffold group with many new bone trabeculae,and repaired completely in the scaffold-cell group.Histological results showed that at 4 weeks after surgery,the defects in the control group were filled with amorphous tissues,subchondral bone formation just occurred in the scaffold group but increased in the scaffold-cell group.At 12 weeks after surgery,trabecular bone structure with no cartilage lacuna was observed in the control group;incomplete subchondral bone formation was observed in the scaffold group,and the cartilage layer was repaired by the fibrous tissues;in the scaffold-cell group,osteochondral defect repair was complete,with the emergence of tidal line,and the newborn cartilage was completely integrated with the surrounding normal tissue in addition to a similar thickness.At 12 weeks after surgery,collagen II basically did not express in the control group,weakly expressed in the scaffold group and highly expressed in the scaffold-cell group.In short,the PHBHOx/collagen composite osteochondral scaffold promotes the repair of articular osteochondral defects in the weight-bearing area.