载三联抗痨药硫酸钙/聚氨基酸人工骨植入脊柱结核病灶内:植骨界面的组织学改变  

Histological changes of the bone-implant interface after calcium sulfate/ polyaminoacid artificial bone carrying triple-anti-tuberculosis drugs is implanted into the spinal tuberculosis focus

作　　者：张卓[1] 孙宇航[2] 耿广起[3] 施建党[3] 王自立[3] 牛宁奎[3] 马文鑫[3] 刘海涛[3] 王骞 

机构地区：[1]宁夏自治区人民医院骨科,宁夏回族自治区银川市750001 [2]宁夏医科大学,宁夏回族自治区银川市750004 [3]宁夏医科大学总医院脊柱骨科,宁夏回族自治区银川市750004 [4]美国南弗罗里达大学药学院,美国33620

出　　处：《中国组织工程研究》2016年第47期7027-7033,共7页Chinese Journal of Tissue Engineering Research

基　　金：国家自然科学基金(81060149)~~

摘　　要：背景:近年来国内外很多学者致力于脊柱结核病灶的局部药物缓释系统及骨缺损植骨材料的研究,但如何把两者有效结合成为具有药物缓释功能的植骨材料,并且切实观察该材料对疾病治疗效果的研究却较为少见。目的:观察兔脊柱结核模型病灶清除部位植入载三联抗痨药异烟肼(H)、利福平(R)、吡嗪酰胺(Z)的硫酸钙/聚氨基酸人工骨后植骨界面骨愈合的组织学变化,评价此载药人工骨在兔脊柱结核模型病灶内的植骨融合能力。方法:将新西兰大白兔36只,随机等分为3组,实验组、对照组为24只建立成功的兔脊柱结核模型,空白对照组为健康兔。实验组植入载三联抗痨药异烟肼、利福平、吡嗪酰胺的硫酸钙/聚氨基酸人工骨;对照组及空白对照组植入未载药硫酸钙/聚氨基酸人工骨。结果与结论:(1)植骨融合部位的脊柱段组织学变化:苏木精-伊红染色显示,人工骨材料植入后2周时,各组动物体内的载药与非载药硫酸钙/聚氨基酸人工骨均被纤维组织覆盖,并与创面紧密连接,植入后4周时植入材料均已明显分解,植入后8周时植入材料已大部分分解完毕,植入后16周后植骨材料已完全消失。实验组标本中,植入后4周已可见骨痂形成,但骨愈合程度在各阶段均晚于空白对照组。对照组骨愈合出现明显停滞。空白对照组4周可见骨痂形成,已初步连接,16周已基本愈合;(2)植骨融合部位的脊柱段组织超微结构:透射电镜及扫描电镜观察显示,植入后实验组成骨细胞可通过材料空隙爬行形成新骨;(3)结果说明:载抗痨药异烟肼、利福平、吡嗪酰胺的硫酸钙/聚氨基酸人工骨植入兔脊柱结核模型病灶清除后的骨缺损部位,载药人工骨在局部有支架作用,在骨缺损区骨细胞能够爬行替代并实现骨界面融合。BACKGROUND：Most researchers have devoted to study the control-release system in spinal tuberculosis focus and implant material for bone defects, but the effective combination to obtain a novel implant material and its treatment outcomes are rarely reported. OBJECTIVE：To observe the histological change of the implant-bone interface after implantation of the calcium sulfate/polyaminoacid artificial bone carrying triple-anti-tuberculosis drugs including isoniazid, rifampicin and pyrazinamide in a rabbit model of spinal tuberculosis, and to assess the fusion ability of the material. METHODS：Thirty-six New Zealand rabbits were randomly divided into experiment, control and blank control groups （n=12 per group）. Models of spinal tuberculosis were established in the rabbits and randomly assigned into either experiment or control groups, fol owed by implantation with the calcium sulfate/polyaminoacid artificial bone carrying triple-anti-tuberculosis drugs including isoniazid, rifampicin and pyrazinamide, or the calcium sulfate/polyaminoacid artificial bone, respectively. Healthy controls received the implantation with calcium sulfate/polyaminoacid artificial bone only. RESULTS AND CONCLUSION：Hematoxylin-eosin staining showed that the artificial bone was covered by fibers and tightly adhered to the wound in each group at 2 weeks after implantation, the graft started to degrade obviously at the 4th week, degraded mostly at the 8th week, and disappeared completely at the 16th week. There was obvious cal us formation at 4 weeks after implantation in the experiment group, but the bone healing was later than that of the blank control group. The bone healing ended in the control group. In the blank control group, cal us formation and early osteogenesis appeared at the 4th week, and healed completely at the 16th week. Transmission electron microscope and scanning electron microscope revealed that osteoblasts could crawl through the gap of materials to form new bone. These results suggest that the calcium sulfate/polya

关 键 词：生物材料 骨生物材料 骨结核 缓释系统 植入物 骨痂 异烟肼 利福平 吡嗪酰胺 硫酸钙/聚氨基酸人工骨 国家自然科学基金 

分 类 号：R318[医药卫生—生物医学工程]