丝素蛋白/羟基磷灰石材料复合骨髓间充质干细胞构建组织工程化软骨

Silk fibroin/hydroxyapatite combined with bone marrow mesenchymal stem cells for construction of tissue engineered cartilage

背景:随着组织工程的兴起,软骨损伤的修复可能性显著地提高,但单一的支架材料均不能符合理想支架,有一定的局限性。目的:观察骨髓间充质干细胞复合丝素蛋白/羟基磷灰石构建组织工程化软骨的可行性。方法:体外分离培养骨髓间充质干细胞,并定向诱导成软骨细胞,与丝素蛋白/羟基磷灰石复合培养,构建膝关节胫骨平台全层关节软骨缺损。54只大白兔单侧膝关节全层软骨缺损模型后随机抽签法分为3组,复合组植入细胞-丝素蛋白/羟基磷灰石复合物;材料组植入单纯丝素蛋白/羟基磷灰石,对照组不行任何植入。植入后8,12周CT检查及组织学检查观察软骨缺损修复情况。结果与结论:植入后8周,复合组关节面不平整,关节间隙增大,形成新生类软骨细胞,基质丰富。材料组关节面塌陷,软骨细胞少量增殖。植入后12周,复合组关节面平整,关节间隙如常。大量软骨细胞出现,与周边软骨色泽一样,支架材料完全降解。材料组关节面不平整,软骨细胞不完全充填,支架材料部分降解。对照组未见修复。提示用骨髓间充质干细胞复合丝素蛋白/羟基磷灰石可形成透明软骨修复动物膝关节全层软骨缺损,显示了丝素蛋白/羟基磷灰石材料作为关节软骨组织工程支架材料的良好生物相容性。

BACKGROUND： With the emergence of tissue engineering, the possibility of repairing the cartilage injury is greatly increased, but single scaffold materials fail to meet ideal scaffold, and have some limitations. OBJECTIVE： To explore the feasibility of silk fibroin/hydroxyapatite combined with bone marrow mesenchymal stem cells （BMSCs） for construction of tissue engineered cartilage METHODS： BMSCs were isolated, cultured and induced into chondrocytes, which were cocultured with silk fibrion/hydroxyapatite to construct full-thickness articular cartilage defects in the platform of knee joints tibial plateau. A total of 45 rabbits with unilateral knee full thickness cartilage defects model were randomly divided into 3 groups. The compound group was implanted with cell-silk fibrion/hydroxyapatite compound; material group was only implanted with silk fibrion/hydroxyapatite; implantation was not given in the control group. The reparation condition of cartilage defects was observed by CT examination and histological examination at 8, 12 weeks after implantation. RESULTS AND CONCLUSION： In the compound group, the articular surface was not flat, the joint space was increased, formed new chondrocyte-like cells and extracellular matrix was extremely rich after 8 weeks. In the material group, articular surface was collapsed and a small amount of chondrocytes were proliferated. After 12 weeks, in the compound group, the articular surface was flat, the joint space was normal; a large number of chondrocytes were emerged, and the color of repaired tissues was closed to surrounding cartilage and scaffolds were completely degraded. In the material group, the articular surface was not flat and cartilage cells did not completely filled, some scaffolds were degraded. The defects were not repaired in the control group. It is indicated that the method of repairing the full-thickness hyaline cartilage defects using BMSCs combined with silk fibroin/hydroxyapatite is feasible, and the silk fibroin/hydroxyapatite can be used as scaffold materials in articular cartilage tissue engineering due to a good biocompatibility.