Objective To investigate the osteogenic activity of the recombinant human bone morphogenetic protein 2 (rhBMP-2)-loaded nano-hydroxyapatite(Nano-HA)composite artificial bone and its capacity to repair rabbit radial bone defects,and to provide a theory basis for clinical treatment of bone defects.Methods Radial bone defect(12 mm)was produced in 36 adult male New Zealand rabbits.Then these rabbits were randomly divided into three groups,with 12 rabbits in each group.Rabbits in group A received the implantation of rhBMP-2-loaded Nano-HA com-posite artificial bone.Rabbits in group B received the implantation of Nano-HA composite artifi-cial bone.Rabbits in group C received no implantation.General observation,serum alkaline phos-phatase(ALP)detection,radiography,histological examination and biomechanical testing were performed 4,8 and 12 weeks after implantation.Results The levels of serum ALP in the three groups significantly increased at 4 weeks after treatment,reached a peak at 8 weeks after treat-ment,and then began to decrease and significantly increased at 12 weeks after treatment(all P <0.05).There were significant differences in ALP levels among the three groups after treatment (P <0.05).Radiography showed total degradation of implants,completion of bone cortex connec-tion and complete repair of bone defects in group A,partial degradation of implants,a lot of bone density shadow,a large amount of porosis and partial repair of bone defects in group B,and frac-ture site smooth hardening absorption,marrow cavity closure and bone nonunion without bone in-growth in group C.Histological examination showed that total degradation of implants,a large a-mount of lamellar bone formation,completion of callus remodeling and repair of bone defects in group A,partial degradation of implants,compact bone formation,a lot of new bone formation and partial repair of bone defects in group B,and a lot of fibrous tissue formation and bone nonunion at fracture site without new bone formation in group C.Compared with group B,Lane-Sandhu ra-diographical and histological scores increased in group A but decreased in group C(P <0.05).In addition,three-point bending test showed that the biomechanical strength in group A was greater than that in group B(P <0.05).Conclusion The rhBMP-2-loaded Nano-HA composite artificial bone has higher osteogenic capability and results in shorter bone defect healing time than Nano-HA artificial bone.It has the potential clinical value in the repair of long bone defects and pro-vides a theoretical basis for the selection of bone defect repair materials.%目的：以纳米羟基磷灰石（Nano-HA）为载体支架，复合重组人骨形态发生蛋白-2（rhBMP-2）构建 Nano-HA 复合 rhBMP-2人工骨（Nano-HA/rhBMP-2复合人工骨），植入兔桡骨缺损，探讨 Nano-HA/rhBMP-2复合人工骨局部成骨活性及修复兔桡骨骨缺损的能力，为临床骨缺损治疗提供理论依据。方法将36只成年的新西兰雄性大白兔随机分为 Nano-HA/rhBMP-2复合人工骨组（A 组）、Nano-HA 人工骨组（B 组）、空白组（C 组）3组，每组12只，制作成桡骨为12 mm 的骨缺损模型。A 组植入 Nano-HA/ rhBMP-2复合人工骨；B 组植入 Nano-HA 人工骨，C 组不植入任何材料。植入后于4、8、12周行大体观察、血清碱性磷酸酶（ALP）检测、X 线摄片、组织学观察及生物力学检测。结果1）与术前比较，3组 ALP 含量术后4周均明显升高（P ＜0．05），术后8周达最高峰（P ＜0．05），之后开始下降，在12周时 ALP 含量均较术前显著升高（P ＜0．05）；3组术后4、8、12周 ALP 含量比较差异均有统计学意义（P ＜0．05）。2）X 线片表现：术后12周 A 组植入材料完全降解，骨皮质连接完成，骨缺损完全修复；B 组材料大部分降解，有大量骨密度影，有大量骨痂形成，骨髓腔基本再通，骨缺损大部分修复；C 组骨折断端光滑硬化吸收，无骨质长入，骨髓腔封闭，形成骨不连。3组术后4、8、12周 Lane-Sandhu X 线骨形成评分 A 组＞B组＞C 组，差异均有统计学意义（P ＜0．05）。3）组织学表现：术后12周 A 组材料完全降解，大量的板层骨形成，骨痂完成塑形，骨缺损修复；B 组材料大部分降解及密质骨形成，有大量新生骨组织，骨缺损大部分修复；C 组骨缺损断端大量的纤维组织形成，未见新骨形成，断端骨不连。3组术后4、8、12周 Lane-Sandhu 组织学骨形成评分 A组＞B 组＞C 组，差异均有统计学意义（P ＜0．05）。4）三点抗弯生物力学检测 A 组标本术后4、8、12周均显著高于B 组（P ＜0．05）。结论Nano-HA/ rhBMP-2复合人工骨比 Nano-HA 人工骨具有更强的成骨能力，明显缩短了骨缺损愈合时间。Nano-HA/ rhBMP-2复合人工骨在修复长骨骨缺损方面具有潜在的临床价值，为临床骨缺损修复材料的选择提供了理论依据。
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