BMP-2多肽/功能化碳纳米管复合材料修复兔颅骨缺损的实验研究  

Experimental study on repairing rabbit skull defect with bone morphogenetic protein 2peptide/functionalized carbon nanotube composite

作　　者：邸运涛 王存阳 朱惠学 于素香 任义行 李晓明 DI Yuntao;WANG Cunyang;ZHU Huixue;YU Suxiang;REN Yixing;LI Xiaoming(Department of Neurosurgery,the Fourth Central Hospital of Baoding City,Baoding Hebei,072350,P.R.China;Key Laboratory for Biomechanics and Mechanobiology of Ministry of Education,Beijing Advanced Innovation Center for Biomedical Engineering,School of Biological Science and Medical Engineering,Beihang University,Bejing.10083.P.R.China;Department of Pathology,the Fourth Central Hospital of Baoding City,Baoding Hebei,072350,P.R.China;Department of Orthopedics,the Fourth Central Hospital of Baoding City,Baoding Hebei,072350,P.R.China)

机构地区：[1]保定市第四中心医院神经外科,北保定072350 [2]北京航空航天大学生物与医学工程学院,生物力学与力生物学教育部重点实验室,北京市生物医学工程高精尖创新中心,北京100083 [3]保定市第四中心医院病理科,河北保定072350 [4]保定市第四中心医院骨科,河北保定072350

出　　处：《中国修复重建外科杂志》2021年第3期286-294,共9页Chinese Journal of Reparative and Reconstructive Surgery

基　　金：国家自然科学基金资助项目(31771042);高等学校学科创新引智计划(B13003);北京航空航天大学博士研究生卓越学术基金。

摘　　要：目的观察并比较多肽通过非共价与共价两种不同结合方式,以及利用羧基(-COOH)和氨基(-NH2)两种不同官能团与材料结合,对兔颅骨缺损修复效果的影响。方法3月龄雄性普通级新西兰白兔21只,将左右两侧顶骨编号1~42号,采用随机数字表法分为5组,对照组(A组,6侧)及材料1、2、3、4组(分别为B、C、D、E组,每组9侧)。所有动物均制备直径12 mm颅骨缺损模型,分别将BMP-2非共价结合的多壁碳纳米管(multi-walled carbon nanotubes,MWCNT)-COOH+左旋聚乳酸[poly(L-lactide),PLLA]、BMP-2非共价结合的MWCNT-NH2+PLLA、BMP-2共价结合的MWCNT-COOH+PLLA、BMP-2共价结合的MWCNT-NH2+PLLA植入B、C、D、E组缺损区。术后4、8、12周取材行CT扫描及三维重建观察,定量分析骨组织再生体积与总体积比值并测量骨密度值;样本切片行HE染色和Masson三色染色组织学观察,定量分析新生骨组织体积比。结果CT扫描及三维重建观察示,随时间延长,A~E组骨缺损被逐渐填充,术后12周时E组骨缺损被完全填充。HE染色和Masson三色染色示,随时间延长,各组新生骨组织体积逐渐增大,术后12周D、E组出现了再生成熟骨组织。定量分析显示,术后4、8、12周,各组骨组织再生体积与总体积比值、骨密度值、新生骨组织体积比随时间增加均呈逐渐增加趋势;且各时间点从A~E组也呈逐渐增加趋势,组间两两比较差异均有统计学意义(P<0.05)。结论通过共价结合方式并利用-NH2将多肽与材料相结合,可以实现最好的骨修复效果。Objective To observe and compare the effects of peptides on the repair of rabbit skull defects through two different binding modes of non-covalent and covalent,and the combination of carboxyl(-COOH)and amino(-NH2)groups with materials.Methods Twenty-one 3-month-old male ordinary New Zealand white rabbits were numbered 1 to42 on the left and right parietal bones.They were divided into 5 groups using a random number table,the control group(group A,6 sides)and the material group 1,2,3,4(respectively group B,C,D,E,9 sides in each group).All animals were prepared with 12-mm-diameter skull defect models,and bone morphogenetic protein 2(BMP-2)non-covalently bound multiwalled carbon nanotubes(MWCNT)-COOH+poly(L-lactide)(PLLA),BMP-2 non-covalently bound MWCNTNH2+PLLA,BMP-2 covalently bound MWCNT-COOH+PLLA,and BMP-2 covalently bound MWCNT-NH2+PLLA were implanted into the defects of groups B,C,D,and E,respectively.At 4,8,and 12 weeks after operation,the samples were taken for CT scanning and three-dimensional reconstruction,the ratio of bone tissue regeneration volume to total volume and bone mineral density were measured,and the histological observation of HE staining and Masson trichrome staining were performed to quantitatively analyze the volume ratio of new bone tissue.Results CT scanning and three-dimensional reconstruction showed that with the extension of time,the defects in groups A-E were filled gradually,and the defect in group E was completely filled at 12 weeks after operation.HE staining and Masson trichrome staining showed that the volume of new bone tissue in each group gradually increased with time,and regenerated mature bone tissue appeared in groups D and E at 12 weeks after operation.Quantitative analysis showed that at 4,8,and 12 weeks after operation,the ratio of bone tissue regeneration volume to total volume,bone mineral density,and the volume ratio of new bone tissue increased gradually over time;and at each time point,the above indexes increased gradually from group A to group E,and the differences

关 键 词：BMP-2 多肽 多壁碳纳米管 颅骨缺损 三维重建 骨修复 兔 

分 类 号：R318.08[医药卫生—生物医学工程]