骨形态发生蛋白-2复合纤维蛋白缓释胶修复骨缺损的实验研究

［摘要］目的　探讨纤维蛋白胶作为骨形态发生蛋白-2（BMP-2）的缓释载体修复骨缺损，促进早期成骨的作用，为临床应用提供实验依据．方法　实验制备纤维蛋白胶/ BMP-2复合物，BMP-2在复合物中的浓度为1 μg/mL．将36只健康成年家兔随机分成3组，均造成双侧桡骨外侧中1/3段长8 mm，宽2 mm，深1 mm的骨缺损．实验组:植入纤维蛋白胶与BMP-2的复合物对骨缺损进行修复；对照组:在骨缺损区单独植入纤维蛋白胶进行修复；空白组:骨缺损区不植入任何材料，骨缺损自然愈合．于术后 2周、4周、8周分期处死动物，每个时间点每组取样本4只，采用X线检查、组织学观察、骨钙素（OC）免疫组化检测骨缺损部位成骨情况．结果　X线检查显示，实验组术后4周，骨痂形成的量较对照组和空白组明显增多．Masson染色显示，实验组术后2周有少量骨基质沉积．对照组骨小梁稀疏．空白组骨缺损区由纤维组织充填，未见新骨形成．术后4周，实验组骨缺损区有较多的新骨形成，骨小梁排列规则，连成网格状．对照组骨小梁仍较稀疏．空白组仅见少量稀疏的骨小梁，小梁间有较多纤维组织充填．骨钙素（OC）免疫组化结果显示:术后第2周，实验组、对照组和空白组OC表达分别达到高峰，其中实验组表达量大于对照组和空白组（P＜0.01）．术后第4周，实验组、对照组和空白组OC表达均明显下降（P＜0.01），但实验组表达量大于对照组和空白组（P＜0.01）．术后8周3组的OC表达无明显差异（P＞0.05）．结论　纤维蛋白胶/BMP-2复合物具有缓慢释放BMP-2的作用，能够持续促进骨缺损区骨组织的再生和钙化，加速骨缺损的愈合，为临床提供一种有效促进骨愈合的方法．

Experimental Study of Fiber Glue as A Carrier Compounded with BMP-2 on Repairing Bone Defect

［Abstract］Objective To investigate the effect of the fibrin glue（FG）as a carrier compounded with BMP-2 on repairing bone defect and stimulating early period bone formation，and to provide the experimental foundation for the clinical application. Methods The fibrin glue compounded with growth factor BMP-2 delivery system was prepared with the consistency of BMP-21 μg/mL. Bone defects（8.00 mm length，2.00mm width and 1.00mm depth）were created in 36 rabbits on the bilateral radius and rabbits were divided into three groups. They were treated with three kinds of implantations，including fibrin compounded with BMP-2 in experimental group，fibrin in control group and no material in blank control group. Rabbits were sacrificed at the end of 2 weeks，4 weeks and 8 weeks after operation，respectively. Then specimens were obtained in each time point and bone formation and osteocalcin（OC）were detected by X-ray，histological section and immunohistochemical method. Results The bone forming activity and bone healing speed in experimental group were significantly better than those of the other groups by X-ray and histological section. Immunohistochemical results showed OC contents were highest and there were significant differences among the three groups in the second week（P < 0.01）. In experimental group， the expression amount of OC decreased in local bone and bone callus organization， and the most significant differences among the three groups appeared at the fourth week（P < 0.01）. There was no difference in the expression of OC between the experimental group and the other groups at the eighth week（P > 0.05）. Conclusion The material with fibrin glue as a carrier compounded with BMP-2 could significantly accelerate the new bone forming， regeneration，mineralization and remodeling，shorten the recovery period，which can provide a clinical method for repairing bone defect.