Abstract:

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 ?C, 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-1shRNA and PEI-Lys in distilled water at 4.0 ?C. Then, the WISP-1shRNA/PEI-Lys loaded hydrogel was formed after incubation of the mixed solution at 37.0 ?C. During tests, the plasmid was released from this hydrogel complex constantly, and enhanced the transfection efficiency of WISP-1shRNA. In addition, silencing WISP-1 results to lower expression of MMP-3 and ADAMTS, and the accumulation of HBP1 in synoviocytes. Therefore, the hydrogel containing WISP-1shRNA is demonstrated an efficient way for the treatment of OA.

Key words: osteoarthritis, biodegradable thermosensitive hydrogel, PLGA-PEG-PLGA, WISP-1