聚乳酸作为骨形态发生蛋白载体修复骨缺损的实验研究

An experimental study of bone defects repaired with bone morphogenetic protein using polylactic acid as carrier

目的探讨聚乳酸（ polylactic acid, PLA）作为骨形态发生蛋白（ bone morphogenetic protein, BMP）载体的可行性及观察其诱导成骨能力。方法手术造成日本大耳白兔左尺骨中上段 12 mm骨缺损实验模型，随机分为实验、对照及空白组，实验组植入以 PLA为载体的 BMP 10 mg、对照组植入以牛松质骨基质为载体的 BMP 10 mg、空白组不做任何处理。术后摄 X线片观察各组不同时相骨缺损修复情况，并于术后第 4、 8、 12周观察各组缺损内组织学变化，图像分析骨小梁的生成量。结果实验组骨生成情况优于对照组，无论是骨连接发生时间还是骨成熟时间，实验组均较对照组提前 2周左右，同期骨生成量也明显多于对照组，而空白组缺损内主要形成纤维组织。结论 PLA可以作为 BMP的载体修复骨缺损，它比异种松质骨基质载体的成骨效果更理想。此外， PLA和其它载体相比还具有以下优点： (1)可在修复骨缺损的过程中逐渐释放 BMP，使缺损部位 BMP维持在有效的浓度； (2)具有一定刚度，并随 PLA的降解逐渐减弱，对骨折具有弹性固定的作用； (3)可根据骨折固定要求将 PLA制成不同的形状； (4)具有良好的生物相容性及可调性。但是，对 PLA相对分子质量及孔径与最佳成骨效果间的关系有待进一步研究。

Objective To study the feasibility of polylactic acid(PLA) as carrier of bone morphogenetic protein(BMP), and observe its results of inducing osteogenesis. Methods A 12 mm bone defect experimental model in the left ulna of rabbits was made, the animals were divided into three groups at random, bovine BMP 10 mg with PLA carrier was implanted into the defect area in the experimental group, bovine BMP 10 mg with bovine cancellous bone matrix carrier was implanted in the control group, and nothing was implanted in the blank group. The osteogenesis of the bone in the defect area was observed by regular roentgenography, the histological changes of the bone defect tissue in 4th, 8th, 12th week after operation were studied and the new bone formation was measured by image analysis. Results The results revealed that the bone defect in the experimental group had excellent repair than that seen in the control and blank group, both bone union and the period of bone mature were earlier than that seen in the control and blank groups. There was fibration in the blank group at 12th week. Conclusion The result indicated that PLA is a material able to be used as a carrier of BMP in inducing osteogenesis, it has a better effect of inducing osteogenesis than xenogenous cancellous bone matrix. Compared with other carriers, PLA has the following advantages: 1)It releases BMP gradually during degradation, so the BMP concentration in bone defect can be maintained effectively. 2)It is a material with some rigidity, so is able to exert flexible fixation of the fractures. 3)It can be shaped to adjust itself for the individual fractures. 4)It has a good histocompatibility and an adjustable property. However, the relationship between the molecule weight, aperture of PLA and the best inducing osteogenesis need a further study.