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KMID : 1377020180150030263
Tissue Engineering and Regenerative Medicine
2018 Volume.15 No. 3 p.263 ~ p.274
In Vitro Anti-Inflammation and Chondrogenic Differentiation Effects of Inclusion Nanocomplexes of Hyaluronic Acid-Beta Cyclodextrin and Simvastatin
Kim Tae-Hoon

Yun Young-Pil
Shim Kyu-Sik
Kim Hak-Jun
Kim Sung-Eun
Park Kyeong-Soon
Song Hae-Ryong
Abstract
The aim of this study was to prepare inclusion nanocomplexes of hyaluronic acid-¥â-cyclodextrin and simvastatin (HA-¥â-CD/SIM) and evaluate in vitro anti-inflammation effects on lipopolysaccharide (LPS)-activated synoviocytes and chondrogenic differentiation effects on rat adipose-derived stem cells (rADSCs). The ¥â-CD moieties in HA-¥â-CD could incorporate SIM to form HA-¥â-CD/SIM nanocomplexes with diameters of 297?350 nm. HA-¥â-CD/SIM resulted in long-term release of SIM from the nanocomplexes for up to 63 days in a sustained manner. In vitro studies revealed that HA-¥â-CD/SIM nanocomplexes were able to effectively and dose-dependently suppress the mRNA expression levels of pro-inflammatory markers such as matrix metallopeptidase-3 (MMP-3), MMP-13, cyclooxygenase-2 (COX-2), a disintegrin and metalloproteinase with thrombospondin motifs-5 (ADAMTS-5), interleukin-6 (IL-6), and tumor necrosis factor (TNF-¥á) in LPS-stimulated synoviocytes. HA-¥â-CD/SIM-treated rADSCs significantly and dose-dependently enhanced mRNA expressions of aggrecan, collagen type II (COL2A1), and collagen type X (COL10A1), implying that HA-¥â-CD/SIM greatly induced the chondrogenic differentiation of rADSCs. Conclusively, HA-¥â-CD/SIM nanocomplexes will be a promising therapeutic material to alleviate inflammation as well as promote chondrogenesis.
KEYWORD
Hyaluronic acid-¥â-cyclodextrin, Simvastatin, Chondrogenesis, Adipose-derived stem cells
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