| For enhanced osteoinductivity to treat effectively with bone defects,the design and fabrication of novel drug delivery systems remain a great challenge.Herein,we for the first time fabricated core-shell ZSM-5/chitosan ellipsoids loaded with pifithrin-?(ZSM-5/CS/PFT? ellipsoids)and SC79-loaded ZSM-5/chitosan(ZSM-5/CS/SC79)porous scaffolds via the freeze-drying synthesis of ZSM-5/CS porous scaffolds followed by loading SC79 drug molecules,respectively.The morphologies,phases pore structure of the powder and scaffolds were studied by means of SEM,TEM,EDS,XRD,FTIR,TG-DTA and so on.The ZSM-5 ellipsoids with long-axis lengths of ~400 nm and short-axis lengths of ~300 nm are constructed by many nanocrystals.The micropores and mesopores that exist respectively within and among the ZSM-5 nanocrystals serve as channels for loading PFT?.The CS on the ZSM-5/CS/PFT? ellipsoids increases drug loading efficiency up to 91.0%,and improves drug sustained release property.The ZSM-5/CS/PFT? ellipsoids possess excellent cytocompatibility,and promote the adhesion,spreading and proliferation of human bone mesenchymal stem cells(hBMSCs).Moreover,the released PFT? from the ZSM-5/CS/PFT? ellipsoids improves the ALP activity of hBMSCs,the mRNA relative expression levels of COL1,OCN and RUNX2,the ECM mineralization and the protein level of ?-catenin.The reason is attributed to the fact that the released PFT? as a p53 inhibitor disrupts the ubiquitinproteasome mediated degradation of ?-catenin,resulting in the significant accumulation of ?-catenin and the downstream transcription of genes involved in cell survival,proliferation and osteogenic differentiation.The excellent in vitro bioactivity,biocompatibility,osteoinductivity of ZSM-5/CS/PFT? ellipsoids suggest that they have great potential for bone impalnts.The ZSM-5/CS/SC79 scaffolds that were obtained in the SC79 solutions with original concentrations of 10,20 and 40 ?M were abbreviated to ZSM-5/CS/SC79 10?M,ZSM-5/CS/SC79 20?M and ZSM-5/CS/SC79 40?M.The ZSM-5/CS/SC79 10?M,ZSM-5/CS/SC79 20?M and ZSM-5/CS/SC79 40?M had the similar drug release trends.At the first 3 days,the SC79 released rapidly from the drug carries,and then the drug release rates decreased gradually with prolonging further time.The drug loading-release tests suggested that the ZSM-5/CS porous scaffolds were fit for drug delivery systems.The ZSM-5/CS scaffolds possessed three-dimensional(3D)interconnected pores,and ZSM-5 ellipsoids were uniformly dispersed on CS films.Both the ZSM-5/CS and ZSM-5/CS/SC79 scaffolds could promote the adhesion,spreading and proliferation of human bone mesenchymal stem cells(hBMSCs).Interestingly,the ZSM-5/CS/SC79 scaffolds had the appropriate drug loading-release properties,and the released SC79 enhanced remarkably the proliferation and osteogenic differentiation of hBMSCs.As compared with ZSM-5/CS control group,the ZSM-5/CS/SC79 scaffolds promoted the ALP activity of h BMSCs,improved the mRNA relative expression levels of osteocalcin(OCN),bone morphogenetic protein-2(BMP-2)and alkaline phosphatise(ALP),and increased the protein level of ?-catenin.The enhanced proliferation and osteogenic differentiation of hBMSCs contributed to the upregulation of Akt kinase by activated Wnt/?-catenin signaling pathway.Moreover,the released SC79 from the ZSM-5/CS/SC79 scaffolds promoted new bone regeneration in cranial defects.Therefore,ZSM-5/CS/SC79 scaffolds as novel and promising therapeutic scaffolds have great applications for defined local bone regeneration. |
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