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1.苏州大学医学部 骨科研究所 苏州 215006
2.上海市中西医结合防治骨与关节病损重点实验室 上海市伤骨科研究所 上海交通大学医学院附属瑞金医院 上海 200025
3.聚合物分子工程国家重点实验室 复旦大学高分子科学系 上海 200433
Published:2018-10,
Received:26 February 2018,
Revised:27 March 2018,
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Ruo-yu Cheng, Wen-guo Cui. Hydrogen Bond Mechanically Enhanced Cholecalciferol Lipo-Hydrogel for Bone Regeneration. [J]. Acta Polymerica Sinica 0(10):1315-1327(2018)
Ruo-yu Cheng, Wen-guo Cui. Hydrogen Bond Mechanically Enhanced Cholecalciferol Lipo-Hydrogel for Bone Regeneration. [J]. Acta Polymerica Sinica 0(10):1315-1327(2018) DOI: 10.11777/j.issn1000-3304.2018.18066.
基于氢键和光交联双交联网络构建力学增强型维生素D
3
脂质体复合水凝胶,并通过药物控释促进成骨分化. 通过甲基丙烯酸酯明胶(GelMA)与载药脂质体的氢键作用,形成双交联网络,实现复合水凝胶体系最大断裂力值和弹性模量均提升至原来的2倍. 通过脂质体对于脂溶性药物维生素D
3
的包载,实现维生素D
3
在水凝胶网络中均匀分散和缓慢释放. 体外研究表明,该复合水凝胶比GelMA有着更显著的促进成骨分化作用,且不影响细胞的增殖黏附. 因此,该类型脂质体增强型水凝胶在拓宽水凝胶装载和控释药物及组织修复方面有良好的前景.
Hydrogel is an excellent candidate for drug delivery and tissue regeneration. However
hydrogel used as drug carriers is facing some problems
including limited optional drug and burst drug release. In addition
hydrogel is still confronting some challenges in the area of mechanical property. Cholecalciferol is a type of vitamin able to promote ossification. However
as a lipophilic drug
it should be taken according to the recommended dosage. That means the carriers must be capable of making hydrophobic drug homodispersed with controlling drug release. In this study
we designed a novel hydrogen bond based mechanical reinforced hydrogel
modified by release-controlling cholecalciferol liposome
as an multifunctional scaffold for promoting osteogenesis during the process of bone regeneration. Specifically
drug-loaded liposome was fabricated and the characteristics of the liposomes were investigated. Further
photo-crosslinkable gelatin derivative (GelMA) was combined with drug loaded liposome by micro-cross linking double network
generated by the interaction between hydrogen bond and hydrogel network
leading to double enhancement in mechanical property both for compression and streching. Furthermore
the ability to control release and support uniform distribution of hydrophobic drug (cholecalciferol) was observed in the composite hydrogel
specifically the sustained release of cholecalciferol lasted for three weeks at least without significant brust release.
In vitro
study also revealed that
this composite hydrogel was proved to have excellent biocompatibility without significant influence on MC3T3-E1 cell adhesion
proliferation
compared with GelMA hydrogel and control groups. After 21 days cultivation
MC3T3-E1 cells cultured with this composite hydrogel exhibited remarkably facilitated osteogenic differentiation
according to the result of ALP stain
ALP analysis and Alizarin red staining. Thus
it is reasonable to believe that this liposome composite hydrogel could provide a promising strategy for extending the application of hydrogel in drug delivery and tissue reconstruction.
脂质体水凝胶控制释放力学增强骨修复
LiposomeHydrogelControl releaseMechanical enhancementBone regeneration
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