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

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 100 μM 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.