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中空多孔钛合金假体加载BMP缓释体及自体BMSCS兔体内成骨的实验研究

Bone Formation in Hollow Porous Titanium Prostheses Loading with BMP Slow-release Combination and Autografting BMSCs in Rabbits

【作者】 罗松

【导师】 蔡谞;

【作者基本信息】 中国人民解放军军医进修学院 , 外科学, 2009, 硕士

【摘要】 目的:本实验以内部加载有骨形态发生蛋白(BMP)缓释体的中空多孔钛合金假体(HPTP)作为骨组织工程构架,观察复合与不复合自体骨髓基质干细胞(BMSCs)时,假体植入兔体内后,其腔内及周围的成骨效果和生物力学性能;探讨通过在假体内部复合自体BMSCS提高局部成骨活性,使中空钛合金假体与周围骨质相对一体化牢固结合,减少假体植入后远期无菌性松动发生率,并为未来人工关节假体的设计制造提供基础实验依据。方法:自行设计中空多孔(孔径2mm)钛合金假体。假体表面与内部均经过羟基磷灰石(HA)喷涂。实验分为两组:中空多孔钛合金加载BMP缓释体组(A组)以及中空多孔钛合金加载BMP缓释体再复合自体BMSCs组(B组),共用大新西兰大白兔18只,每组9只。分别将各组假体横向植入兔后肢双侧股骨髁。实验动物饲养至第3、8、12周时处死取材,通过大体观察、普通光镜、荧光显微镜以及骨组织形态计量学等途径对假体周围及内部的骨生成情况进行观察;第12周时,每组取6例标本进行生物力学检测,以比较分析各组假体的力学性能。用CHISS2004软件进行统计分析,计量资料以均数±标准差((?)±s)表示。结果:A、B组假体大体观察结果相似。组织学观察可见A、B组在各时间点上骨组织均随时间增长逐步增多,12周时中空腔内成骨最多,尤以BMP缓释体部位成骨明显;骨质可经假体孔洞长入腔内,连通内外骨质;假体空腔内骨组织计量学表明,在3周时A、B两组骨生成率的差异无统计学意义,P>0.05;8周和12周时B组的骨生成率高于A组,P<0.01,具有显著性差异。在生物力学测试中,B组的拔出力普遍高于A组,但进行统计学分析后发现P>0.05,其差异无统计学意义。结论:一、中空多孔钛合金假体加载BMP缓释体复合自体BMSCs可比不复合BMSCs更有效地促进假体内部的骨生长,使假体与周围骨质更紧密结合,提高假体植入的远期稳定性。二、在加载BMP缓释体的中空多孔钛合金假体内部复合自体BMSCs对假体的力学拔出力量并无明显影响。三、中空多孔金属假体设计思路可行,周围骨质可通过孔隙长入假体内,并与假体内新生骨质融合。相较于传统实心假体,孔隙处骨质既填补了金属的空缺,又能连接假体内外骨质,加强假体植入的牢固性。四、金属表面行羟基磷灰石喷涂可使假体与周围骨质牢固结合。本实验从体内角度证明内部复合有自体BMSCs的中空多孔假体较未复合BMSCs的假体具有更强的假体内成骨能力,为未来人工假体的设计制造提供了基础实验支持。

【Abstract】 Objective:This study was to compare the osteogenic potential and biomechanical performance of Hollow Porous Titanium Prostheses(HPTP) loading with BMP slow-release combination and Hollow Porous Titanium Prostheses(HPTP) loading with BMP slow-release combination and autografting BMSCs in rabbits;and to discuss the feasibility of enhancing the integration of Hollow Porous Titanium Prostheses(HPTP) with the bone around it.We hope the results will provide an experimental basis for the study of hollow porous artificial joint prostheses and other bone-regeneration implants,and will be beneficial for the design and improvement of biological artificial joint.Methods:We designed a HPTP with many holes(2mm in diameter).The internal surface and part of superficies extema which will be implanted in bone of the prostheses were spray coated with hydroxyapatite(HA).There were 2 groups in this research: Hollow Porous Titanium Prostheses(HPTP) loading with BMP slow-release combination(group A),Hollow Porous Titanium Prostheses(HPTP) loading with BMP slow-release combination and autografting BMSCs(group B).Eighteen New Zealand white rabbits(4~6 months old) were used totally,9 in each group.All the implants were placed in the femoral condyles of rabbits transversely.3,8,12 weeks after operation,we took out corresponding specimens,and studied the bone formation around and within the prostheses with common light microscopy, fluorescence microscopy and software for norphometry.Besides,6 specimens in each group were used for biomechanical tests at the 12th week point.CHISS2004 software was used for statistical analysis,and measurement data were expressed in the form of mean value±standard deviation((?);±s).Results:There were no obviously different in outward appearance between Group A and B. 3 to 12 week after operation,bone tissue regenerate quickly,especially where the BMP slow-release combination was.Bone tissue could grow into the holes on porous prostheses,make the bone inside integrate with the bone outside.The morphometry results show that bone regeneration rate of group B is significantly higher than group A at 8 and 12 week after operation,p<0.01;but the difference has no significance at 3 week after operation,p>0.05.In biomechanical tests,there was no statistical difference between the pull-out forces of group B and group A.Conclusion:1.Hollow Porous Titanium Prostheses(HPTP) loading with BMP slow-release combination and autografting BMSCs offer better conditions for bone regeneration than Hollow Porous Titanium Prostheses(HPTP) loading with BMP slow-release combination.,which can improve integration of prostheses and bone tissue significantly.2.BMSCs has no effect on the pull-out force of Hollow Porous Titanium Prostheses(HPTP) loading with BMP slow-release combination3.The idea for HPTP is feasible,Bone tissue could grow into the holes on porous prostheses,make the bone inside integrate with the bone outside.4.HA coating of the HPTP can integrate with bone tissue very well.Our experiment in vivo shows that Hollow Porous Titanium Prostheses(HPTP ) loading with BMP slow-release combination and autografting BMSCs offer better conditions for bone regeneration than Hollow Porous Titanium Prostheses(HPTP) loading with BMP slow-release combination.It offers elementary experiment support for the design of artificial joint in the further.

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