结合聚消旋乳酸与人重组骨形态发生蛋白-2的髓内钉对骨折愈合的促进作用  

Effect of intramedullary nails coated with PDLLA ＋ rhBMP-2 on fracture healing

作　　者：鲁谊[1] 吕厚山[1] 王满宜[2] 

机构地区：[1]北京大学医学部人民医院骨科,100044 [2]北京积水潭医院创伤骨科

出　　处：《中华创伤骨科杂志》2007年第4期340-344,共5页Chinese Journal of Orthopaedic Trauma

基　　金：北京市卫生重点学科资助项目

摘　　要：目的探讨结合有聚消旋乳酸（PDLLA）与人重组骨形态发生蛋白-2（rhBMP-2）生物涂层的髓内钉通过可持续释放对骨折愈合的影响。方法48只兔建立胫骨骨折模型，分为对照组和实验组，分别以普通克氏针及按一定比例结合有PDLLA与rhBMP-2（500μg 10mg）的克氏针作为髓内钉固定骨折，在术后4、8周分别行x线评分、DEXA测量骨密度、三点弯曲试验测量最大应力与负荷、组织学观察骨折部位的成骨情况，并进行统计学比较。选择12只家兔观察结合PDLLA与rhBMP-2的髓内钉的异物反应情况；进一步对手术前、术后即刻、术后24h、48h、1周、2周、4周、8周髓内钉表面的生物涂层进行定量分析，通过ELISA法测量相应时间涂层中rhBMP-2的含量，以了解其降解程度。结果术后4、8周时，x线评分证明实验组中骨膜增生、骨痂生长及骨小梁塑形情况明显强于对照组；DEXA测量实验组中在骨折局部的骨密度明显高于对照组；生物力学测量实验组的最大负荷与应力明显高于对照组（P〈0.05）；组织学观察实验组的骨折周围成骨更明显、骨膜反应更强烈，不同时间段的组织标本中均未见有明显的炎症反应。在置入髓内钉的过程中涂层表面存在一定的磨损（7．60％±4．64％）．术后24h～1周生物涂层内rhBMP-2的降解最为迅速（从73．48％±1．16％降到29．35％±6．89％），之后在低水平渐趋稳定。结论将给合有PDLLA与rhBMP-2的髓内钉应用于动物骨折模型中，可有效地促进骨折愈合，同时对动物不存在明显的毒副作用。Objective To investigate the effect of rhBMP-2 combined with poly （D, L-lactide） （PDLLA） which is continually released from the coating of intramedullary nails （IMN） on fracture healing. Methods The tibial fractures of rabbits （ n = 48 ） were intramedullary stabilized with uncoated Kirschner wires （control group, n = 24） and Kirsehner wires with rhBMP-2 ＋ PDLLA coating （experimental group, n = 24） . X-ray examinations, DEXA （dual energy X-ray absorptiometry） for BMD （bone mineral density）, biomeehanieal three bending tests to measure the max stress and loading, and histological evaluations were all performed at 4 and 8 weeks after operation. Data obtained were statistically analyzed. The immune reaction against coated IMN was evaluated by histology on the similar animal models （ n = 12）. Next, we weighed the coating of IMN, and measured the level of rhBMP-2 in the biological coating by ELISA right after operation, 24 h, 48 h, 1, 2, 4, and 8 weeks after operation. Results At 4 and 8 weeks postoperatively, the X-my scores demonstrated better callus formation in the coated groups than in the uncoated groups. The results of DEXA revealed greater BMD in the former. Three bending testing revealed significantly greater maximum load and stress in the rhBMP-2 treated groups than in the controls. Histological evaluations showed stronger periosteal reaction and significantly increased mineralization at the fracture sites due to the rhBMP-2 effects. In addition, no immune reaction was detected. During operation, the wear and tear of coating was found to be 7.60% ±4.64%. From 24 h to 1 week, the rhBMP-2 was released rapidly （73.48% ±1. 16% to 29.35% ± 6. 89% by ELISA） and then became comparatively stable as time went on. Conclusions Application of IMNs coated with rhBMP-2 and PDLLA is feasible and has significantly promoting effect on fracture healing progression. The cold coating technique can produce stable and safe coating of IMNs with little side effect.

关 键 词：骨钉 骨形态发生蛋白质类 骨折愈合 生物涂层 骨折固定术 髓内 

分 类 号：R686[医药卫生—骨科学]