| Stem cells are ideal seed cells for damaged tissue repair owing to their ability of self-renewal and multi-differentiation.Among them,mesenchymal stem cells(MSCs)are considered to be the most promising seed cell types for clinical treatment,because of easy harvest and mature in vitro culturing technology.The classical protocol for inducing the differentiation of MSCs into osteoblasts is involving chemical inducers,such as dexamethasone,?-glycerophosphate sodium,and vitamin C.Studies have shown that dexamethasone(DEX)has both promoting and inhibiting effects on osteogenic differentiation,depending on dose,time period of action,cell type and stage of the cell.The current view is that 10~-77 mol/L DEX has the most significant osteogenic effect,which can promote the differentiation of MSCs into osteoblasts,and promote matrix synthesis and calcification.Due to the high hydrophobicity of DEX,there is a technical challenge to maintain a constant concentration of it in an aqueous environment.In recent years,with the development of nanotechnology,more and more nanomaterials have been applied to the field of drug release.?-Cyclodextrin(?-CD)has a special cylindrical hydrophobic interior and hydrophilic outer rim structure,the cavity of which has good inclusion properties for many kinds of hydrophobic molecules by means of host-guest interactions.Therefore,?-CD has received more and more attention in the fields of nanometer self-assembly,drugs and gene carriers over recent years.However,to date no relevant literature or patent report on the application of?-CD as a DEX-loaded carrier for osteogenic differentiation of MSCs.In this study,?-CD was used as a drug-loading matrix,and two kinds of DEX controlled-release systems were prepared via host-guest interactions.The main research work is as follows:(1)The first type of DEX-loaded nanoparticles(CD/DEX)was obtained by simply loading DEX in?-CD through host-guest interaction.(2)Adamantane(AD)is a commonly used guest molecule,with a large inclusion constant to?-CD and the most stable structure with?-CD.AD-DEX complex can be formed by by esterification between DEX and adamantane formic acid(AD-COOH),and then the complexes were loaded into?-CD via host-guest reaction to obtain the second type of DEX-loaded nanoparticles(CD/AD-DEX).Fourier transform infrared spectroscopy(FT-IR),mass spectrometry(MS-ESI),nuclear magnetic resonance(~1H-NMR),ultraviolet-visible absorption spectroscopy(UV-vis),particle size distribution characterization results showed that both DEX and AD-DEX was successfully loaded on?-CD,with a high drug loading rate and a size of around hundred nanometers.In vitro drug release experiments showed that both DEX-loaded nanoparticles achieved controlled release of DEX.MTT experimental results showed that the drug-loaded matrix(?-CD)has good biocompatibility and the results of cell differentiation experiments proved that CD/AD-DEX,CD/DEX significantly enhanced the osteogenic differentiation of rBMSCs than free DEX drug.Based on the sustained release characteristics of CD/AD-DEX and CD/DEX and their high efficiency in inducing osteogenic differentiation,these two DEX-delivery systems have the potential to promote bone defect repair in vivo by achieving sustained release of DEX at the bone defect site and inducing the osteogenic differentiation of stem or progenitor cells. |
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