In Vitro Anti-Inflammation and Chondrogenic Differentiation Effects of Inclusion Nanocomplexes of Hyaluronic Acid-Beta Cyclodextrin and Simvastatin

  • Tae-Hoon Kim
  • Young-Pil Yun
  • Kyu-Sik Shim
  • Hak-Jun Kim
  • Sung Eun KimEmail author
  • Kyeongsoon ParkEmail author
  • Hae-Ryong SongEmail author
Original Article


The aim of this study was to prepare inclusion nanocomplexes of hyaluronic acid-β-cyclodextrin and simvastatin (HA-β-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 β-CD moieties in HA-β-CD could incorporate SIM to form HA-β-CD/SIM nanocomplexes with diameters of 297–350 nm. HA-β-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-β-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-α) in LPS-stimulated synoviocytes. HA-β-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-β-CD/SIM greatly induced the chondrogenic differentiation of rADSCs. Conclusively, HA-β-CD/SIM nanocomplexes will be a promising therapeutic material to alleviate inflammation as well as promote chondrogenesis.


Hyaluronic acid-β-cyclodextrin Simvastatin Chondrogenesis Adipose-derived stem cells 



This study was supported by the grants provided by the Bio and Medical Technology Development Program of NRF funded by the Korean government, MSIP (NRF-2017M3A9F5030273 and NRF-2017M3A9B3063640) and a grant provided by the Korea Health Technology R&D Project, Ministry of Health and Welfare, Republic of Korea (HI15C1665).

Compliance with ethical standards

Conflict of interest

The authors declare no conflict of interest.

Ethical statement

Animal experimental procedures were approved by the Institutional Animal Care and Use Committee of the Korea University Medical Center (KUIACUC-2014-268 and KUIACUC-2014-5).


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Copyright information

© The Korean Tissue Engineering and Regenerative Medicine Society and Springer Science+Business Media B.V., part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Orthopedic SurgeryKonkuk University School of MedicineSeoulKorea
  2. 2.Department of Orthopedic Surgery and Rare Diseases Institute, Korea University Guro HospitalKorea University College of MedicineSeoulKorea
  3. 3.Department of Biomedical Science, Korea University College of MedicineKorea UniversitySeoulKorea
  4. 4.Department of Systems Biotechnology, College of Biotechnology and Natural ResourcesChung-Ang UniversityAnseong-siKorea

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