论著·基础研究

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
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  • 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
相宜(1994—),女,硕士生;电子信箱: xy9408@163.com。

网络出版日期: 2019-11-02

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
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  • 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 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)。

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。

本文引用格式

相宜 1 , 2 , 刘立立 1 , 2 , 崔文国 1 , 2 . 携载抗菌黏性脂质体的水凝胶构建及促进骨修复的研究[J]. 上海交通大学学报(医学版), 2019 , 39(9) : 947 . DOI: 10.3969/j.issn.1674-8115.2019.09.003

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.
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