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.