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骨形态发生蛋白-2壳聚糖微球复合组织工程支架修复兔股骨髁部骨缺损的实验研究
引用本文:黄鑫,孟国林,刘建,袁志,熊卓,李国臣,白峰,禚文昆,马煜,吕荣,王军,郝赋.骨形态发生蛋白-2壳聚糖微球复合组织工程支架修复兔股骨髁部骨缺损的实验研究[J].中华创伤骨科杂志,2010,12(4).
作者姓名:黄鑫  孟国林  刘建  袁志  熊卓  李国臣  白峰  禚文昆  马煜  吕荣  王军  郝赋
作者单位:1. 第四军医大学西京医院骨科,西安,710032
2. 清华大学机械工程系
基金项目:国家自然科学基金资助 
摘    要:目的 探讨重组人骨形态发生蛋白-2(rhBMP-2)壳聚糖缓释微球复合聚乳酸-聚羟乙酸/磷酸三钙(PLGA/TCP)支架修复骨缺损的可行性和有效性.方法 取健康成年新西兰大白兔45只,在40只实验动物股骨髁部制备0.6 cm×1.0 cm骨缺损.实验分4组:A组:缺损组,B组:用PLGA/TCP空白支架修复骨缺损,C组:用等量rhBMP-2复合PLGA/TCP支架修复骨缺损,D组:用rhBMP-2壳聚糖微球复合PLGA/TCP支架修复骨缺损,每组10只动物.另5只动物为正常对照组(E组).应用X线、Micro-CT和组织病理学等方法检测术后4、12 周各实验组骨缺损修复效果.结果 术后4周X线片示:A组无新骨形成.B组有少量新生骨影像形成,C、D组骨缺损部位均有新骨影像形成.术后12周,Micro-CT结果显示:D组骨密度、骨体积分数、骨小梁厚度、骨小梁数目等指标均优于B组和C组,差异均有统计学意义(P<0.05),A组末检测到上述指标.术后4剧,D组可见大量骨组织形成,有部分成熟的骨小梁,PLGA/TCP支架大部分被降解.吸收.术后12周,D组支架和微球完全降解.骨缺损被成熟骨取代;B、C、D组骨长入率分别为5.78%±1.21%、37.26%±6.45%、74.25%±8.91%,3组之间比较差异均有统计学意义(P<0.05).结论 复合rhBMP-2壳聚糖微球的PLGA/TCP支架具有良好的骨缺损修复效果,临床应用前景较好.

关 键 词:骨形态发生蛋白质类  股骨  壳聚糖  组织工程  骨缺损

Poly(DL-lactic-glycolic acid)/tricalcium phosphate scaffolds loaded with recombinant human bone morphogenetic protein-2 chitosan microspheres for treatment of bone defects in rabbits
Abstract:Objective To investigate the feasibility and efficacy of using the poly(DL-lactic-glycolic acid)/tricalcium phosphate(PLGA/TCP)scaffolds loaded with recombinant human bone morphogenetic protein-2(rhBMP-2)chitosan microspheres to treat bone defects in rabbits.Methods The rhBMP-2 chitosan microspheres were incorporated into the PLGA/TCP scaffold.The composites of rhBMP-2 microspheres and the PLGA/TCP were then used to bridge the bone defects(diameter: 0.6 cm,depth: 1.0 cm)at the condyle of the left femur in rabbits.Altogether 45 rabbits were randomized into 5 groups in the present study.In group A(n = 10)the defects were not treated.The PLGA scaffold was used in group B(n = 10),the rhBMP-2/PLGA scaffold in group C(n = 10),and the rhBMP-2 micorsphere/PLGA scaffold in group D(n = 10).Group E(n = 5)was the normal control.Ⅹ-ray,Micro-CT and histological studies were conducted to identify new bone formation in groups A to D at 4 and 12 weeks after surgery.Results At 4 weeks postoperatively,plenty new bone and mature trabecular bone were observed,and most of the PLGA/TCP scaffolds were degraded in group D.At 12 weeks postoperatively,the PLGA/TCP scaffolds and chitosan microspheres were completely degraded,and the bone defects were filled with mature bone in group D.In addition,the ratio of new bone formation was significantly higher in group D(74.25%±8.91%)than in group B(5.78% ±1.21%)and group C(37.26% ±6.45%)(P < 0.05).Conclusion The PLGA/TCP composites loaded with rhBMP-2 microspheres are effective in stimulating new bone formation when used to bridge bone defects in rabbits,highlighting their potential application in clinical settings.
Keywords:Bone morphogenetic proteins  Femur  Chitosan  Tissue engineering  Bone defect
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