中国组织工程研究

中国组织工程研究 ›› 2019, Vol. 23 ›› Issue (18): 2833-2841.doi: 10.3969/j.issn.2095-4344.1671

• 组织工程骨及软骨材料 tissue-engineered bone and cartilage materials • 上一篇    下一篇

复合N-乙酰半胱氨酸分子可片段化聚甲基丙烯酸甲酯骨水泥的制备和性能

赵康全1，皮  斌2，沙卫平1，葛建飞1，杨惠林2，王黎明1
  

  1. 1张家港市第一人民医院骨科，江苏省苏州市  215000；2苏州大学附属第一医院骨科，江苏省苏州市  215000
  • 收稿日期:2019-01-14 出版日期:2019-06-28 发布日期:2019-06-28
  • 通讯作者: 王黎明，副主任医师，张家港市第一人民医院骨科，江苏省苏州市 215000
  • 作者简介:赵康全，男，1990年生，江苏省苏州市人，汉族，2016年苏州大学毕业，硕士，医师，主要从事骨科生物材料研究。
  • 基金资助:

    苏州市科教兴卫青年科学基金项目(KJXW2017059)，项目负责人：赵康全

Preparation and properties of degradable polymethyl methacrylate bone cement incorporated with　N-acetyl cysteine

Zhao Kangquan1, Pi Bin2, Sha Weiping1, Ge Jianfei1, Yang Huilin2, Wang Liming1 
  

  1. 1Department of Orthopedics, Zhangjiagang First People’s Hospital, Suzhou 215000, Jiangsu Province, China; 2Department of Orthopedics, the First Affiliated Hospital of Soochow University, Suzhou 215000, Jiangsu Province, China
  • Received:2019-01-14 Online:2019-06-28 Published:2019-06-28
  • Contact: Wang Liming, Associate chief physician, Department of Orthopedics, Zhangjiagang First People’s Hospital, Suzhou 215000, Jiangsu Province, China
  • About author:Zhao Kangquan, Master, Physician, Department of Orthopedics, Zhangjiagang First People’s Hospital, Suzhou 215000, Jiangsu Province, China
  • Supported by:

    the Science and Education Youth Science Foundation of Suzhou, No. KJXW2017059 (to ZKQ)

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摘要：

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文题释义：
聚甲基丙烯酸甲酯骨水泥：于1958年首次被应用于全髋关节置换后，聚甲基丙烯酸甲酯骨水泥在骨科中的应用越来越多，其本身是非生物降解性材料，合成这种骨水泥的液体组分主要是甲基丙烯酸甲酯单体，在与粉剂混合后，单体便聚合形成高分子聚合物，该聚合物的主链是极其稳定的C-C键长链，这种高分子长链无法在体内进行胞外分解形成小分子物质，而且相互缠绕交联，在包裹各种粉剂制成骨水泥之后形成巨大的团块，无法被体内巨噬细胞吞噬。  
2-亚甲基-1，3-二氧杂环庚烷：为热稳定液体，易燃、无毒，有一定的吸湿性，对酸敏感，酸性条件下会形成酯类物质；在一定条件下，能够发生自身的开环聚合，形成聚酯，或利用其化学结构中的乙烯基发生聚合，形成支链上含七元杂环的聚合物；与其他物质发生共聚反应的主要方式是，与含乙烯基的某些单体发生自由基的开环共聚，所形成的共聚物主链上有酯基，侧链能够按不同要求包含不同的功能基团，这种共聚反应是合成功能性生物降解材料的好方法。
 
 
背景：聚甲基丙烯酸甲酯骨水泥在脊柱成形和脊柱后凸成形治疗中被广泛使用，但其部分关键性能尚有改善空间。
目的：制备复合N-乙酰半胱氨酸的分子可片段化聚甲基丙烯酸甲酯骨水泥，评估其抗压强度、凝固性能、表面特征、药物释放、降解性能、生物相容性和促成骨性能。
方法：制备传统聚甲基丙烯酸甲酯骨水泥(记为C-PMMA骨水泥)及添加25 mmol/L N-乙酰半胱氨酸、5% 2-亚甲基-1，3-二氧杂环庚烷的聚甲基丙烯酸甲酯骨水泥(记为NAC/5%MDO骨水泥)，检测骨水泥的凝固时间、微观结构、降解性能及体外N-乙酰半胱氨酸释放率。将小鼠成骨细胞前体细胞MC3T3-E1分3组培养，分别加入传统骨水泥浸提液、NAC/5%MDO骨水泥浸提液与常规培养液(对照组)，培养1，3，5 d后，CCK-8法检测细胞增殖；培养1，3，7 d后，苏木精-伊红染色观察细胞形态；培养3 d后，扫描电镜观察细胞黏附形态；成骨诱导21 d后，茜素红染色观察成骨性能。
结果与结论：①C-PMMA骨水泥组与NAC/5%MDO骨水泥组凝固时间比较差异无显著性意义(P > 0.05)；②扫描电镜显示，C-PMMA骨水泥组与NAC/5%MDO骨水泥组断面都无孔隙结构；③NAC/5%MDO骨水泥能在PBS中缓慢持续释放N-乙酰半胱氨酸；④传统骨水泥浸泡于醋酸前后的数均分子质量无明显变化，NAC/5%MDO骨水泥浸泡于醋酸1，5 d后的数均分子质量明显低于浸泡前(P < 0.05)；⑤3组细胞不同时间点的细胞增殖比较差异无显著性意义(P > 0.05)；苏木精-伊红染色可见3组细胞形态、密度表现良好；扫描电镜显示，细胞贴附于NAC/5%MDO骨水泥表面，形态良好；茜素红染色显示，NAC/5%MDO骨水泥组染色较传统骨水泥组深；⑥结果表明复合N-乙酰半胱氨酸的分子可片段化聚甲基丙烯酸甲酯骨水泥，具有良好的细胞相容性及降解、缓释、促成骨性能。

关键词: 生物材料, 聚甲基丙烯酸甲酯, 骨水泥, 甲基丙烯酸甲酯, 力学强度, 乙酰半胱氨酸, 骨诱导性, 生物降解, 细胞毒性

Abstract:

BACKGROUND: Polymethyl methacrylate bone cement is popular in kyphoplasty and vertebrolplasty, while some of its key properties still need improvement.

OBJECTIVE: To prepare degradable polymethyl methacrylate bone cement incorporated with N-acetyl cysteine and search for its compressive strength, operability, surface appearance, N-acetyl cysteine release, degradation property, biocompatibility and osteogenic capacity.
METHODS: Traditional polymethyl methacrylate bone cement and degradable polymethyl methacrylate bone cement incorporated with 25 mmo/L N-acetyl cysteine and 5% 2-methylene-1,3-dioxepane (NAC/5%MDO) were prepared. Setting time of bone cement, microstructure, degradation property and N-acetyl cysteine release in vitro were detected. MC3T3-E1 cells were allotted into three groups, and cultured with traditional polymethyl methacrylate bone cement, NAC/5%MDO extract and conventional culture solution (control group), respectively for 1, 3, and 5 days. The cell proliferation was detected by cell counting-kit 8 assay. Cell morphology was observed by hematoxylin-eosin staining. The cell adhesion was observed by scanning electron microscope after 3 days of culture. The osteogenic capacity of bone cement was detected by Alizarin red staining at 21 days.
RESULTS AND CONCLUSION: (1) There was no significant difference in the setting time of bone cement between polymethyl methacrylate and NAC/5%MDO groups (P > 0.05). (2) Scanning electron microscope observed that no pore structure was observed on the bracken face in the polymethyl methacrylate and NAC/5%MDO groups. (3) NAC/5%MDO bone cement could release N-acetyl cysteine in PBS slowly and continuously. (4) Number-average molecular of NAC/5%MDO bone cement at 1 and 5 days after immersed in acetic acid was significantly decreased compared with baseline (P < 0.05), and traditional polymethyl methacrylate bone cement did not change significantly. (5) The cell proliferation was insignificant difference among groups (P > 0.05). Hematoxylin-eosin staining results revealed good cell morphology and density in each group. Scanning electron microscope observed that the cell adhered to the NAC/5%MDO bone cement with good shape. The Alizarin red staining in the NAC/5%MDO group was deeper than that in the traditional polymethyl methacrylate. (6) These results indicate that degradable polymethyl methacrylate bone cement incorporated with N-acetyl cysteine possesses good cytocompatibility, degradation property, sustained-release and osteogenic capacity.

Key words: biomaterial, polymethyl methacrylate, bone cement, methyl methacrylate, mechanical strength, N-acetyl cysterine, osteogenic capacity, biodegradation, cytotoxicity

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