Dexamethasone-Loaded Beta-Cyclodextrin For Osteogenic Induction Of Mesenchymal Stem/Progenitor Cells And Bone Regeneration

Dexamethasone (DEX) is a glucocorticoid commonly used as anin vitroosteogenic inducer of mesenchymal stem/progenitor cells (abbreviated MSCs). However, several studies investigating the effects of glucocorticoids on bone regeneration through systemic injections have demonstrated negative impacts of the drugs at high concentration on the healing of hard tissues. These contrasting evidences suggest that application of glucocorticoids should be limited to low dosages but at the same time a long enough treatment period is preferred, which prompted us to evaluate the effects of different local release systems of DEX on MSC differentiation and bone repair. Two types of DEX-loaded beta-cyclodextrin (CD) complexes, including CD/DEX and CD/AD-DEX, were fabricatedviahost-guest interactions and characterized by FTIR, 1H-NMR, MS-ESI, and UV-vis. The results demonstrated that these CD-based assemblies released DEX in differentiated profiles, with CD/DEX releasing significantly faster than CD/AD-DEX. Although CD/DEX were slightly more powerful than CD/AD-DEX in inducing rat bone marrow MSCs (rBMSCs) into osteogenic lineagein vitro, CD/AD-DEX was advantageous over CD/DEX in accelerating bone regeneration over a time period of 4 weeks in a rat tibia defect model. The results suggest that DEX-loaded assembliesviahost-guest interactions are flexible in modulating DEX release patterns and have great potential in bone tissue engineering.