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用于骨组织再生的载辛伐他汀热敏PLGA-PEG-PLGA水凝胶的控释:体外和体内特性

Controlled release of simvastatin-loaded thermo-sensitive PLGA-PEG-PLGA hydrogel for bone tissue regeneration: in vitro and in vivo characteristics.

作者信息

Yan Qi, Xiao Li-Qun, Tan Lei, Sun Wei, Wu Tao, Chen Liang-Wen, Mei Yan, Shi Bin

机构信息

The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory for Oral Biomedical Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, People's Republic of China.

Department of Clinical Laboratory, the First College of Clinical Medical Science, China Three Gorges University, Yichang, China.

出版信息

J Biomed Mater Res A. 2015 Nov;103(11):3580-9. doi: 10.1002/jbm.a.35499. Epub 2015 May 29.

Abstract

Reports on the local delivery of drug loaded injectable hydrogels for bone regeneration are currently limited. This study assessed the effect of controlled simvastatin (SIM) release from a thermo-sensitive hydrogel in vitro and in vivo. We successfully manufactured and evaluated thermo-sensitive poly(d,l-lactide-co-glycolide)-poly(ethylene glycol)-poly(d,l-lactide-co-glycolide) triblock copolymers (PLGA-PEG-PLGA) loaded with SIM. The osteogenic effect of this hydrogel was tested in vitro and in vivo. MC-3T3 E1 cells proliferation and osteoblastic differentiation was analyzed after cultivation with the hydrogel extracts. Cells co-cultured with SIM/PLGA-PEG-PLGA extracts showed an increase in mineralization and osteogenic gene expression compared to the other two groups. Additionally, the characteristics of this composite in vivo were demonstrated using a rat bone defect model. The bone defects injected with SIM/PLGA-PEG-PLGA hydrogel showed increased new bone formation compared to samples treated with PLGA-PEG-PLGA and control samples. The results of this study suggest that SIM/PLGA-PEG-PLGA might provide potential therapeutic value for bone healing.

摘要

目前,关于用于骨再生的载药可注射水凝胶局部递送的报道有限。本研究评估了热敏水凝胶中辛伐他汀(SIM)控释在体外和体内的效果。我们成功制备并评估了负载SIM的热敏聚(d,l-丙交酯-共-乙交酯)-聚(乙二醇)-聚(d,l-丙交酯-共-乙交酯)三嵌段共聚物(PLGA-PEG-PLGA)。在体外和体内测试了这种水凝胶的成骨作用。在用该水凝胶提取物培养后,分析了MC-3T3 E1细胞的增殖和成骨细胞分化。与其他两组相比,与SIM/PLGA-PEG-PLGA提取物共培养的细胞矿化和成骨基因表达增加。此外,使用大鼠骨缺损模型证明了这种复合材料在体内的特性。与用PLGA-PEG-PLGA处理的样品和对照样品相比,注射了SIM/PLGA-PEG-PLGA水凝胶的骨缺损显示出新骨形成增加。本研究结果表明,SIM/PLGA-PEG-PLGA可能为骨愈合提供潜在的治疗价值。

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