Effects of thermosensitive chitosan-gelatin based hydrogel containing glutathione on Cisd2-deficient chondrocytes under oxidative stress

Yung-Hsin Cheng; Eddy Chavez; Kun-Ling Tsai; Kai-Chiang Yang; Wei-Ting Kuo; Yi-Ping Yang; Shih-Hwa Chiou; Feng-Huei Lin

doi:10.1016/j.carbpol.2017.05.069

Effects of thermosensitive chitosan-gelatin based hydrogel containing glutathione on Cisd2-deficient chondrocytes under oxidative stress

Carbohydr Polym. 2017 Oct 1:173:17-27. doi: 10.1016/j.carbpol.2017.05.069. Epub 2017 May 29.

Authors

Yung-Hsin Cheng¹, Eddy Chavez², Kun-Ling Tsai³, Kai-Chiang Yang⁴, Wei-Ting Kuo⁵, Yi-Ping Yang⁶, Shih-Hwa Chiou⁷, Feng-Huei Lin⁸

Affiliations

¹ Department of Education and Research, Taipei City Hospital, Taipei, Taiwan; Department and Institute of Pharmacology, National Yang-Ming University, Taipei, Taiwan. Electronic address: yunghsin@ym.edu.tw.
² Institute of Biomedical Engineering, College of Engineering and College of Medicine, National Taiwan University, Taipei, Taiwan. Electronic address: eddydake@hotmail.com.
³ Department of Physical Therapy, College of Medicine, National Cheng Kung University, Tainan, Taiwan. Electronic address: kunlingtsai@mail.ncku.edu.tw.
⁴ School of Dental Technology, College of Oral Medicine, Taipei Medical University, Taipei, Taiwan. Electronic address: pumpkin@tmu.edu.tw.
⁵ Institute of Biomedical Engineering, College of Engineering and College of Medicine, National Taiwan University, Taipei, Taiwan. Electronic address: u9783854@cmu.edu.tw.
⁶ Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan. Electronic address: molly0103@gmail.com.
⁷ Department and Institute of Pharmacology, National Yang-Ming University, Taipei, Taiwan. Electronic address: shchiou@vghtpe.gov.tw.
⁸ Institute of Biomedical Engineering, College of Engineering and College of Medicine, National Taiwan University, Taipei, Taiwan; Institute of Biomedical Engineering and Nanomedicine, National Health Research Institutes, Miaoli, Taiwan. Electronic address: double@ntu.edu.tw.

PMID: 28732855
DOI: 10.1016/j.carbpol.2017.05.069

Abstract

Aging is considered as a primary risk factor in the development of osteoarthritis (OA) which associated with mitochondrial dysfunction and oxidative stress. CDGSH iron sulfur domain 2 (Cisd2) deficiency causes mitochondrial dysfunction and drive premature aging. In the present study, thermosensitive chitosan-gelatin based hydrogel containing glutathione was developed as injectable drug delivery system for administration by minimal invasive surgery for the treatment of OA. Cisd2 deficiency (Cisd2^-/-) mouse induced pluripotent stem cells-derived chondrocytes were established and characterized. The results suggested that 100μM of glutathione may be an optimal concentration to treat Cisd2^-/- chondrocytes without cytotoxicity. The developed hydrogel showed sustained release profile of the glutathione and could decrease the reactive oxygen species level. Post-treatment of glutathione-loaded hydrogel could rescue Cisd2^-/- chondrocytes from oxidative damage via increasing catalase activity, down-regulation of inflammation, and decreasing apoptosis. These results suggest that thermosensitive glutathione-loaded hydrogel may be a potential antioxidant therapeutic strategy for treating Cisd2^-/- chondrocytes in the near future.

Keywords: CDGSH iron sulfur domain 2; Glutathione; Hydrogel; Oxidative stress.

MeSH terms

Animals
Autophagy-Related Proteins
Carrier Proteins
Chitosan / chemistry*
Chondrocytes / drug effects*
Drug Delivery Systems
Gelatin / chemistry*
Gene Knockout Techniques
Glutathione / chemistry*
Hydrogels / chemistry*
Mice
Nerve Tissue Proteins / deficiency
Oxidative Stress*

Substances

Autophagy-Related Proteins
Carrier Proteins
Hydrogels
Nerve Tissue Proteins
Noxp70 protein, mouse
Gelatin
Chitosan
Glutathione