血管内皮生长因子缓释系统复合成骨诱导的骨髓间质干细胞修复骨缺损

背景：从目前文献报道来看，生长因子缓释系统在骨科方面的应用研究主要集中在软骨修复方面，关于复合组织工程骨修复骨缺损的研究报道较少。 目的：构建复合组织工程骨，观察其修复骨缺损的效果。 方法：①通过血管内皮生长因子、肝素和纤维蛋白胶的不同组合构建复合支架缓释系统，经检测选取最优组种植成骨诱导的骨髓间质干细胞构建复合组织工程骨。②36只SD大鼠制备股骨干骨缺损模型后随机分为3组，分别植入上述复合组织工程骨和复合支架缓释系统，空白对照组不植入任何材料，3组均予内固定。③ELISA方法检测样本释放的血管内皮生长因子浓度以评价复合支架缓释系统的缓释性能；于植入后1，4，12，24周行X射线检查及骨组织碱性磷酸酶染色评价各组动物骨缺损修复水平。 结果与结论：经血管内皮生长因子/肝素/纤维蛋白修饰的纳米晶胶原基骨复合支架缓释系统在体外环境缓释30 d后依然高浓度释放血管内皮生长因子，且缓释曲线平直；动物实验中植入的复合组织工程骨在24周内完全降解，骨缺损修复完成，骨缺损部位碱性磷酸酶活性明显高于复合支架缓释系统组、空白对照组。结果显示该复合支架缓释系统具有优异的缓释性能，在该缓释系统上种植成骨诱导的骨髓间充质干细胞后，能够提高骨缺损修复的速度和质量。

Vascular endothelial growth factor delivery system combined with bone marrow mesenchymal stem cell induced by osteogenesis for repair of bone defects

BACKGROUND:Present studies have reported that the delivery system of growth factors applied in orthopedics is focused on the repair of cartilage. However, the report of using composite tissue engineering bone to repair bone defect is scarce. OBJECTIVE:To construct a composite scaffold of nano-hydroxyapatite/collagen (nHAC) modified by bone marrow mesenchymal stem cells (BMSCs) with osteogenic induction and controlled releasing vascular endothelial growth factor (VEGF) delivery system constituted of VEGF, heparin (HP) and fibrin (FB), and investigate the effect of repair of bone defect. METHODS:Composite scaffold delivery system was constructed with different combinations of VEGF, HP and FB. Then osteogenic induced BMSCs were seeded onto the nHAC scaffolds loaded with the optimal controlled releasing VEGF delivery system. Animal models of femoral bone defect were established. A total of 36 SD rats were randomly divided into 3 groups: VEGF/HP/FB/nHAC/BMSCs group, VEGF/HP/FB/nHAC group and control group, all groups administratered with internal fixation. The releasing capacity of VEGF was estimated by ELISA. X ray and alkaline phosphatase (ALP) activity observation were performed at 1, 4, 12, 24 weeks after implantation to evaluate the repair of bone defects in each group. RESULTS AND CONCLUSION: nHAC modified by controlled releasing drug delivery system constituted of VEGF, HP and FB still released VEGF at a high concentration at 30 days in vitro, and the releasing curve was flat. The composite scaffold in animal model was completely degraded at 24 weeks. Bone defects were repaired well and ALP activity in bone defective parts was significantly higher in VEGF/HP/FB/nHAC/BMSCs group than that in VEGF/HP/FB/nHAC and control groups. nHAC modified by controlled releasing drug delivery system constituted of VEGF, HP and FB has a better releasing characteristic, and the composite scaffold of VEGF/HP/FB/nHAC/MSCs can promote the speed and quality of bone repair in bone defect rat models.