镁合金支架复合基因修饰的BMSCs构建关节软骨及修复软骨缺损的作用

软骨组织工程支架尚未涉及金属材料，存在脆性大，力学性能差等缺陷，不能完全满足关节软骨缺损修复时承载需要。前期研究发现自主专利镁合金可降解，预实验提示镁合金能促进软骨细胞的粘附、增殖及分化，且力学性能极佳。本项目拟在此基础上，通过激光钻孔法制备JDBM镁合金软骨组织工程支架，应用扫描电镜、元素图谱和X线衍射分析该支架在生物学环境中的降解性能，采用有限元模型探讨其孔隙率、孔径与降解性能的关系；在分子水平研究镁合金支架对基因修饰的BMSCs向软骨细胞分化增殖的影响，探讨期间该材料对软骨细胞转录因子Sox9及蛋白聚糖和Ⅱ型胶原等mRNA及其蛋白产物的作用；分析镁合金支架复合基因修饰后的BMSCs异位成软骨及修复软骨缺损的能力，阐明镁合金支架复合基因修饰的BMSCs修复软骨缺损的可行性、有效性，最终研制并筛选出具有优良力学性能及生物学活性的镁合金软骨组织工程支架，为组织工程修复软骨缺损奠定基础。

Scaffolds for cartilage tissue engineering, which has not been made of metal materials, have some disadvantages such as brittleness and poor mechanical property. These scaffolds can not fully meet the requirement of repairing the articular cartilage defects. Previous study found that the novel patent magnesium alloy, with excellent biocompatibility and suitable mechanical property, could easily degrade in biological environment and promote the adhesion, proliferation and differentiation of chondrocytes in vitro. In this study, the JDBM magnesium alloy scaffolds for cartilage tissue engineering are fabricated using laser drilling method, and their degradation behavior are examined using scanning electron microscopy, energy disperse spectroscopy and X-ray diffraction analysis in the biological environment. The effects of the magnesium alloy scaffolds combined with gene-modified BMSCs on the differentiation and proliferation of chondrocytes are investigated at the molecular level, and the effects of the scaffolds on the expression of transcription factor Sox9, proteoglycan and type Ⅱ collagen are explored using real time polymerase chain reaction and western blot methods during the differentiation of chondrocytes. Meanwhile, the ability of ectopic chondrogenesis, and the feasibility and effectiveness of the magnesium alloy scaffolds combined with gene-modified BMSCs for repairing cartilage defects are evaluated. Ultimately the magnesium alloy scaffolds, with suitable mechanical property and excellent biological activity, are developed for cartilage tissue engineering. This study is expected to lay the foundation for the repair of cartilage defects via tissue engineering technology.