上海交通大学学报（医学版）

上海交通大学学报（医学版） ›› 2019, Vol. 39 ›› Issue (9): 947-.doi: 10.3969/j.issn.1674-8115.2019.09.003

• 论著·基础研究 • 上一篇    下一篇

携载抗菌黏性脂质体的水凝胶构建及促进骨修复的研究

相宜 1, 2，刘立立 1, 2，崔文国 1, 2   

  1. 1. 苏州大学骨科研究所，苏州 215000；2. 上海交通大学医学院附属瑞金医院，上海市伤骨科研究所，上海市中西医结合防治骨与关节病损重点实验室，上海 200025
  • 出版日期:2019-09-28 发布日期:2019-11-02
  • 通讯作者: 崔文国，电子信箱：wgcui80@hotmail.com。
  • 作者简介:相宜（1994—），女，硕士生；电子信箱： xy9408@163.com。
  • 基金资助:
    国家自然科学基金（51873107）；上海市人才发展资金（2018099）；上海市教育委员会高峰高原学科建设计划（20171906）；上海交通大学医学转化交叉基金（ZH2018ZDA04）

Fabrication of an antibacterial hydrogel laden with adhesive liposomes for bone repairment

XIANG Yi1, 2, LIU Li-li1, 2, CUI Wen-guo1, 2   

  1. 1. Institute of Orthopaedics, Soochow University, Suzhou 215000, China; 2. Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Disease, Shanghai Institute of Traumatology and Orthopaedics, Ruijin Hospital, Shanghai Jiao Tong University of Medicine, Shanghai 200025, China
  • Online:2019-09-28 Published:2019-11-02
  • Supported by:
    National Natural Science Foundation of China, 51873107; Shanghai Talent Development Fund, 2018099; Shanghai Municipal Education Commission—Gaofeng Clinical Medicine Support, 20171906; Shanghai Jiao Tong University “Medical and Research”Program, ZH2018ZDA04）。

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摘要： 目的 ·构建一种携载抗菌黏性脂质体的水凝胶（ A-LIP-PEG），探究其抗菌及促进骨修复作用。方法 ·基于脂质体和多巴胺的席夫碱反应，制备黏性脂质体（ A-LIP）。将 A-LIP和巯基化的聚乙二醇（ 4SH-PEG）混合，用 Ag+交联 4SH-PEG制备复合脂质体水凝胶。通过 A-LIP对骨形态发生蛋白 2（bone morphogenetic protein 2，BMP-2）的包载，实现 BMP-2在水凝胶网络中均匀分散和缓慢释放。采用粒度仪考察 A-LIP的粒径和电位；采用透射电镜观察 A-LIP的形态；采用冲洗黏附实验评估 A-LIP的黏性；通过 CCK-8验证 A-LIP-PEG的生物相容性；通过骨髓间充质干细胞的碱性磷酸酶测定及茜素红 S染色评定其促成骨活性。结果 ·体外研究表明， A-LIP对软组织有很强的黏附性； A-LIP-PEG对金黄色葡萄球菌有明显的抑制作用； A-LIP-PEG具有较脂质体水凝胶（ LIP-PEG）更显著的促进成骨分化作用，且不影响细胞的增殖。结论 ·该 A-LIP-PEG在拓宽水凝胶装载和控释药物及抗菌、骨修复方面有良好的前景。

关键词: 黏性脂质体, 抗菌, 水凝胶, 骨修复

Abstract:

Objective · To construct an antibacterial hydrogel laden with adhesive liposomes (A-LIP-PEG) for bone repair. Methods · Adhesive liposomes (A-LIP) were fabricated based on the Schiff-based reaction between dopamine and the liposome. To prepare the liposome composite hydrogel, the A-LIPs were mixed with thiolated polyethylene glycol (4SH-PEG) which was then crosslinked with Ag+. Bone morphogenetic protein 2 (BMP-2) was loaded in the A-LIPs for its uniform dispersion and sustained release in the hydrogel network. The size distribution and zeta-potential of the A-LIPs were characterized with a particle size analyzer. The morphology of the A-LIPs was observed under transmission electron microscope. Flushing test was employed to examine the viscidity of the A-LIPs, and CCK-8 assay was conducted to demonstrate the biocompatibility of the A-LIP-PEG. Osteogenic activity of the A-LIP-PEG was evaluatedalkaline phosphatase assay and alizarin red S staining in bone marrow mesenchymal stem cells (BMSCs). Results · Strong adhesion toward soft tissue of the A-LIPs was indicatedin vitro study. A-LIP-PEG showed significant inhibition on Staphylococcus aureus. A-LIP-PEG showed superior promotion of osteogenic differentiation to hydrogel laden with liposomes (LIP-PEG), without disrupting cell proliferation. Conclusion · The A-LIP-PEG developed in this study shows nopotential to expand the application of hydrogels to drug delivery, antibacteria and bone repair.

Key words: adhesive liposome, antibacteria, hydrogels, bone repair

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