纳米羟基磷灰石/胶原复合材料结合血管内皮生长因子修复兔桡骨缺损

Nano-hydroxyapatite/collagen materials combined with vascular endothelial growth factor for repairing bone defects of rabbit radius

背景:纳米羟基磷灰石/胶原复合材料(nano-hydroxyapatite/collagen,NHAC)是一种理想的骨组织工程支架替代材料,血管内皮生长因子(vascular endothelial growth factor,VEGF)是一种促进血管生成最强的生长因子,加入到NHAC中使其缓慢释放,来说明其良好的骨组织修复能力。目的:探讨NHAC结合VEGF修复骨缺损的效果。设计、时间及地点:随机对照动物实验,于2008-10/2009-01在中南大学湘雅医学院动物实验室完成。材料:将纳米羟基磷灰石粉末和胶原蛋白粉末按8∶2的比例调和制备NHAC人工骨。再将2μgVEGF与调和好的纳米羟基磷灰石/胶原蛋白混合固体粉末以1.8∶1的质量比调和制备NHAC/VEGF人工骨。每块人工骨含有纳米羟基磷灰石粉末0.5g、胶原蛋白0.125g、VEGF150ng。方法:建立兔单侧桡骨1cm缺损动物模型36只,按随机原则分为3组。空白组骨断端不做任何处理,NHAC组骨缺损端植入NHAC人工骨,NHAC/VEGF组骨缺损端植入NHAC/VEGF人工骨。主要观察指标:在术后2,4,8周,每组各取4只兔子通过大体观察、X射线片、病理组织切片以及骨密度测定等评价骨愈合的程度。结果:X射线摄片检查:在各个时间段,NHAC/VEGF组骨痂的生长量及骨缺损的修复程度均比NHAC组和空白组好,且NHAC组好于空白组。骨密度测定:术后各时间点的骨密度测定两两比较差异有显著性意义(P均<0.05)。组织学检查NHAC/VEGF组在胶原纤维、成骨细胞及骨小梁的生成情况方面好于NHAC组和空白组,且NHAC组好于空白组。结论:NHAC与VEGF复合骨具有良好的诱导成骨作用,使骨细胞增生活跃,骨折愈合加快,可作为一种新型复合人工骨修复骨缺损。

BACKGROUND： Nano-hydroxyapatite/collagen （NHAC） is an ideal substitute for tissue engineered stent. Vascular endothelial growth factor （VEGF） is a kind of growth factor that can promote vascularization and slowly release NHAC. This indicated a good bone tissue repair function. OBJECTIVE： To investigate the effect of NHAC combined with VEGF in repairing bone defects. DESIGN, TIME AND SETTING： The randomized controlled animal study was performed at the Animal Laboratory, Xiangya Medical College, Central South University from October 2008 to January 2009. MATERIALS： Nano-hydroxyapatite powder and collagen protein powder were mixed and prepared into NHAC artificial bone according to the ratio of 8：2.2 pg of VEGF and NHAC were mixed and prepared into NHAC/VEGF artificial bone according to the ratio of 1.8： 1. Each artificial bone contained 0.5 g nano-hydroxyapatite powder, 0.125 g collagen protein and 150 ng VEGF. METHODS： Thirty-six healthy rabbits whose left radiuses were cut off 1 cm were divided into three groups. The wounds of the rabbits in blank group were sewed up directly without any treatment of the bone. The bone defects of the rabbits in NHAC group were repaired with NHAC artificial bones and the NHAC/VEGF group with NHAC/VEGF artificial bones. MAIN OUTCOME MEASURES： After 2, 4 and 8 weeks, 4 rabbits in each group were killed to evaluate whether they have significant differences of bone healing according to general observation, radiograph, pathological section and bone density test. RESULTS： Radiograph showed that osteotylus growth and the repairing of bone defects in the NHAC/VEGF group were better than in the blank group and NHAC group. It was better in the NHAC group than in the blank group. The difference in bone density of two groups in the same time was significant （P 〈 0.05）. Histology examination showed that the growth of collagen fiber, osteoblasts and bone trabecula was better in the NHAC/VEGF group compared with the NHAC group and blank group, and it was better in the NHAC group than in the blank group. CONCLUSION： The artificial bone of NHAC composited with VEGF has a good function in osteoinduction, activating the growth of osteocytes, fasting the healing of the bone, and can be used as a new type of composite artificial bone to repair bone defect.