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Controlled WISP-1 shRNA Delivery Using Thermosensitive Biodegradable Hydrogel in the Treatment of Osteoarthritis

Controlled WISP-1 shRNA Delivery Using Thermosensitive Biodegradable Hydrogel in the Treatment of Osteoarthritis

作     者:Gong Yubao Ma Hecheng Liu Jianguo 

作者机构:Department of Bone and Joint First Hospital of Jilin University Changchun 130021 China 

出 版 物:《Journal of Bionic Engineering》 (仿生工程学报(英文版))

年 卷 期:2015年第12卷第2期

页      面:285-293页

核心收录:

学科分类:0710[理学-生物学] 071010[理学-生物化学与分子生物学] 081704[工学-应用化学] 07[理学] 08[工学] 0817[工学-化学工程与技术] 070305[理学-高分子化学与物理] 080501[工学-材料物理与化学] 0805[工学-材料科学与工程(可授工学、理学学位)] 0703[理学-化学] 

基  金:Project supported by the National Natural Science Foundation of China (Grant No. 51273081) and Changchun Science and Technology Plan Project (Grant No. 12SF20) and Graduate Innovation Fund of Jilin University project ( No. 20121112) 

主  题:osteoarthritis biodegradable thermosensitive hydrogel PLGA-PEG-PLGA WISP-1 

摘      要:This paper presents a new method of delivering shRNA with biodegradable, thermosensitive PLGA-PEG-PLGA hydrogels for gene treatment of osteoarthritis (OA). OA is a chronic debilitating disease. Without the proper treatment and prognosis, it may result in the loss of joint function in aged people. Currently, gene therapy targeted on WISP-1 has emerged as an alternative method for OA treatment. In order to constantly release shRNA at 37.0 ℃, we synthetized the hydrogels via ring-opening copolymerization of lactide (LA) and glycolide (GA) using Polyethylene glycol (PEG Mn = 1000) and stannous octoate (Sn(Oct)2, 95%) as the macroinitiator and catalyst. First, the PLGA-PEG-PLGA copolymer was mixed with WISP- 1 shRNA and PEI-Lys in distilled water at 4.0 ℃. Then, the WISP-lshRNA/PEI-Lys loaded hydrogel was formed after incubation of the mixed solution at 37.0 ℃. During tests, the plasmid was released from this hydrogel complex constantly, and enhanced the transfection efficiency of WISP-1 shRNA. In addition, silencing WISP-1 results to lower expression of MMP-3 and ADAMTS, and the accumulation of HBP 1 in synoviocytes. Therefore, the hydrogel containing WISP-1 shRNA is demonstrated an efficient way for the treatment of OA.

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