含聚乳酸-羟基乙酸共聚物的新型磷酸钙骨水泥体内降解性能研究

IN VIVO DEGRADABLE PROPERTIES OF A NOVEL INJECTABLE CALCIUM PHOSPHATE CEMENT CONTAINING POLY LACTIC-CO-GLYCOLIC ACID

目的探讨含聚乳酸-羟基乙酸共聚物(poly lactic-co-glycolic acid,PLGA)的新型磷酸钙骨水泥(calcium phosphate cement,CPC)(CPC/PLGA)体内降解性能,为临床试验奠定基础。方法按照45%磷酸氢钙、45%部分结晶磷酸钙、10%PLGA比例,制备CPC/PLGA。健康成年新西兰兔32只,体重2.2～3.0 kg,雌雄各半;随机分为CPC/PLGA组(实验组,n=17)及CPC组(对照组,n=15)。两组实验动物制备双侧股骨内侧髁直径4.5 mm、深1.5 cm骨缺损模型,右侧骨缺损分别采用CPC/PLGA及CPC修复,左侧不作处理作为空白对照。术后观察实验动物一般情况,术后2、4、8、16、24周两组取材行组织学观察、骨形态计量学分析,术后8周及16周实验组取材行扫描电镜观察。结果实验动物均存活至实验结束。组织学观察显示,随时间延长,实验组CPC/PLGA逐渐降解,并有新生骨小梁从边缘长入其中,并且增粗、增长,24周时材料基本降解,被新生骨小梁取代;对照组CPC降解明显较实验组延迟。实验组术后总骨组织含量百分比为44.9%±23.7%,显著高于对照组的25.7%±10.9%(t=3.302,P=0.001);实验组术后4周骨组织含量百分比与对照组比较,差异无统计学意义(P>0.05),8、16、24周均显著高于对照组,差异有统计学意义(P<0.05)。扫描电镜观察结果显示,实验组术后8周CPC/PLGA降解后形成孔径为100～300μm孔隙;随着时间延长,16周时新生骨小梁长入孔隙内,并与残余骨水泥牢固结合。结论 CPC/PLGA植入兔体内后具有良好的降解性能,有望成为一种良好骨移植材料。

Objective To investigate the in vivo degradable properties of new calcium phosphate cement （CPC） containing poly lactic-co-glycolic acid （PLGA） so as to lay a foundation for the future clinical application. Methods A novel CPC containing PLGA （CPC/PLGA） was prepared according to a ratio of 45% dicalcium phosphate anhydrous ： 45% partially crystallized calcium phosphates ： 10% PLGA. Thirty-two adult New Zealand rabbits （weighing 2.2-3.0 kg, male or female in half） were divided into the experimental group （n=17） and the control group （n=15）. The bone defect models of the bilateral femoral condyles （4.5 mm in diameter and 1.5 cm in depth） were made by drilling hole. Defect at the right side was repaired with CPC/PLGA in the experimental group and with CPC in the control group, while defect at the left side was not treated as blank control. The general condition of rabbits was observed after operation; the histological observation and bone histomorphometric analysis were performed at 2, 4, 8, 16, and 24 weeks; and scanning electronic microscope （SEM） observation was performed at 8 and 16 weeks after operation. Results All rabbits survived to the end of experiment. The histological observation showed： CPC/PLGA degraded gradually, and the new-born bone trabecula ingrew; bone trabeculae became rough and strong; and CPC/ PLGA almost biodegraded at 24 weeks in the experimental group. The CPC degradation was much slower in the control group than in the experimental group. The total bone tissue percentage was 44.9%± 23.7% in the experimental group, and 25.7%±10.9% in the control group, showing significant difference between 2 groups （t=3.302, P=0.001）; and the bone tissue percentage showed significant difference between 2 groups at 8, 16, and 24 weeks （P 〈0.05）. The results of SEM observation showed that the pore size was 100-300 μm at 8 weeks after operation, new-born bone trabecula grew into the pores and combined strongly withresidual cement in the experimental group. Conclusion Novel CPC/PLGA has good in vivo degradable properties, and it can be an ideal bone substitute in future clinical application.