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浙江大学学报（医学版）
浙江大学学报（医学版）  2017, Vol. 46 Issue (6): 600-608    DOI: 10.3785/j.issn.1008-9292.2017.12.05
骨组织代谢及再生专题     
力学增强型生物玻璃—陶瓷支架材料促进骨再生修复性能研究
陈立峰1(),杨贤燕2,马锐1,*(),朱玲华3
1. 浙江大学校医院外科, 浙江 杭州 310027
2. 浙江加州国际纳米技术研究院, 浙江 杭州 310058
3. 浙江大学医学院附属邵逸夫医院外科, 浙江 杭州 310016
Application of mechanically reinforced 45S5 Bioglass®-derived bioactive glass-ceramic porous scaffolds for bone defect repairing in rabbits
CHEN Lifeng1(),YANG Xianyan2,MA Rui1,*(),ZHU Linghua3
1. Department of General Surgery, Zhejiang University Hospital, Hangzhou 310027, China
2. Zhejiang California International NanoSystems Institute, Zhejiang University, Hangzhou 310058, China
3. Department of General Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310016, China
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摘要：

目的: 构建一种低熔点含硼、锌生物玻璃（BG-ZnB）力学增强型生物玻璃-陶瓷的多孔支架材料，并探究BG-ZnB含量对支架的结构、力学性能和骨再生效率的影响。方法: 将质量分数为0%、2%、4%的BG-ZnB复合45S5生物活性玻璃通过石蜡微球造孔成型，经900℃烧结分别形成45S5/ZB0、45S5/ZB2、45S5/ZB4三种玻璃-陶瓷多孔支架；测定三种玻璃-陶瓷多孔支架的物相组成、孔隙率和压缩性能。36只雄性新西兰大白兔随机分为45S5/ZnB0组、45S5/ZnB2组和45S5/ZnB4组，将三种多孔支架置入兔骨缺损模型中，分别在第6周和第16周通过X射线摄片、显微CT三维结构重建和组织切片染色等方法检测大白兔骨缺损模型支架的骨再生效率；采用HE染色、Masson三色染色和EnVision二步法染色分析新生骨内生长情况。结果: 力学增强型生物玻璃-陶瓷与45S5生物活性玻璃的物相基本一致，但烧结后的支架在外观上有细微变形。45S5/ZnB2组和45S5/ZnB4支架骨架表面晶粒烧结更为致密，抗压强度较45S5/ZnB0支架明显提高（均P < 0.05）。支架植入后6周和16周时，45S5/ZnB2组和45S5/ZnB4组成骨率和骨小梁密度高于45S5/ZnB0组（均P < 0.05），新生骨、Ⅰ型胶原蛋白和骨钙素表达量较45S5/ZnB0组增加。结论: 低熔点高活性BG-ZnB助烧结工艺能构建出力学增强型生物玻璃-陶瓷多孔支架材料，可为研发骨损伤修复材料奠定实验基础。
关键词： 股骨/损伤;  骨代用品;  硼;  锌;  玻璃;  二氧化硅;  生物相容性材料;  材料试验;  陶瓷制品;  骨再生;  胶原;  生物力学    
Abstract:

Objective: To evaluate the application of mechanically reinforced 45S5 Bioglass®-derived glass ceramic porous scaffolds for repair of bone defect in rabbits. Methods: The BG-ZnB powders were added into the 45S5 Bioglass® powder/paraffin microsphere mixtures and were sintered at 900℃ to obtain porous scaffolds with highly bioactive BG-ZnB of 0%, 2% or 4% of mass fraction (denoted as 45S5/ZnB0, 45S5/ZnB2, 45S5/ZnB4). Phase composition, porosity and compression properties of three kinds of as-sintered scaffolds were characterized by X-ray analysis, mercury porosimetry, and mechanical test. Thirty-six male New Zealand rabbits with critical-sized femoral bone defects were randomly divided into three groups (45S5/ZnB0 group, 45S5/ZnB2 group and 45S5/ZnB4 group, 12 for each), and were implanted with three kinds of porous scaffolds respectively. X-ray, micro-CT three-dimensional reconstruction and tissue slice staining were used to detected the efficiency of bone regeneration at 6 and 16 weeks after operation. The growth of newly formed bone was observed using HE, Masson staining and EnVision method. Results: Phase compositions of 45S5/ZnB2 and 45S5/ZnB4 were the same with 45S5/ZnB0, but the average pore size and porosity of the scaffolds were decreased with the increase of BG-ZnB content. 45S5/ZnB2 and 45S5/ZnB4 scaffolds exhibited higher compressive strength, osteogenesis and trabecular density than those of the 45S5/ZnB0 scaffold (all P < 0.05). With the mechanical reinforcement of BG-ZnB increased, the content of new bone, collagen type I and osteocalcin increased. Conclusion: Low-melt BG-ZnB-assisted sintering is a promising approach to improve the mechanical strength of 45S5 Bioglass®.
Key words: Femur/injuries    Bone substitutes    Boron    Zinc    Glass    Silicon dioxide    Biocompatible materials    Materials testing    Ceramics    Bone regeneration    Collagen    Biomechanics
收稿日期: 2017-01-18 出版日期: 2017-12-25
CLC:  R318.08  
基金资助: 浙江省教育厅科研项目(Y201533880);浙江省自然科学基金(LY15H030011);浙江省医药卫生科技计划(2018KY650)
通讯作者: 马锐     E-mail: clf007@126.com;0013419@zju.edu.cn
作者简介: 陈立峰(1971-), 男, 硕士, 副主任医师, 主要从事骨再生和功能重建方面的研究; E-mail:clf007@126.com; https://orcid.org/0000-0001-5188-8589
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引用本文:

陈立峰,杨贤燕,马锐,朱玲华. 力学增强型生物玻璃—陶瓷支架材料促进骨再生修复性能研究[J]. 浙江大学学报（医学版）, 2017, 46(6): 600-608.

CHEN Lifeng,YANG Xianyan,MA Rui,ZHU Linghua. Application of mechanically reinforced 45S5 Bioglass®-derived bioactive glass-ceramic porous scaffolds for bone defect repairing in rabbits. J Zhejiang Univ (Med Sci), 2017, 46(6): 600-608.

链接本文:

http://www.zjujournals.com/med/CN/10.3785/j.issn.1008-9292.2017.12.05    或    http://www.zjujournals.com/med/CN/Y2017/V46/I6/600

图 1  三种支架及其主要成分的X射线衍射图谱
图 2  三种支架内部断面电镜所见
($\bar x \pm s$)
支架种类 45S5:BG-ZnB 石蜡/BG-ZnB 致孔剂尺寸(μm) 平均孔径(μm) 孔隙率(%) 贯通孔(>50 μm，%) 抗压强度(MPa)
与45S5/ZnB0比较，*P < 0.05.BG-ZnB:低熔点含锌、硼生物玻璃.
45S5/ZnB0 100:0 65:35 350 327±3 75.1±2.5 38.2±2.1 3.3±1.8
45S5/ZnB2 98:2 65:35 350 323±5 72.6±1.7 37.7±1.1 15.6±2.3*
45S5/ZnB4 96:4 65:35 500 315±7 71.2±1.8 37.5±1.5 13.6±2.4*
表 1  三种支架的材料组成、孔结构参数和抗压强度
图 3  置入不同支架6周和16周时股骨缺损部位X射线图像
图 4  置入不同支架6周和16周时股骨缺损部位显微CT重建的三维图像
图 5  术后6周和16周时置入不同支架组显微CT定量分析缺损骨再生情况比较
图 6  置入不同支架6周和16周时缺损骨组织学表现(HE染色)
图 7  置入不同支架6周和16周时缺损骨组织学表现(Masson三色染色)
图 8  置入不同支架6周和16周时缺损骨组织中骨钙素表达(EnVision二步法染色)
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