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- W3152258907 endingPage "120718" @default.
- W3152258907 startingPage "120718" @default.
- W3152258907 abstract "Mesenchymal stem cell-derived exosomes (MSC-exos), with its inherent capacity to modulate cellular behavior, are emerging as a novel cell-free therapy for bone regeneration. Herein, focusing on practical applying problems, the osteoinductivity of MSC-exos produced by different stem cell sources (rBMSCs/rASCs) and culture conditions (osteoinductive/common) were systematically compared to screen out an optimized osteogenic exosome (BMSC-OI-exo). Via bioinformatic analyses by miRNA microarray and in vitro pathway verification by gene silencing and miRNA transfection, we first revealed that the osteoinductivity of BMSC-OI-exo was attributed to multi-component exosomal miRNAs (let-7a-5p, let-7c-5p, miR-328a-5p and miR-31a-5p). These miRNAs targeted Acvr2b/Acvr1 and regulated the competitive balance of Bmpr2/Acvr2b toward Bmpr-elicited Smad1/5/9 phosphorylation. On these bases, lyophilized delivery of BMSC-OI-exo on hierarchical mesoporous bioactive glass (MBG) scaffold was developed to realize bioactivity maintenance and sustained release by entrapment in the surface microporosity of the scaffold. In a rat cranial defect model, the loading of BMSC-OI-exo efficiently enhanced the bone forming capacity of the scaffold and induced rapid initiation of bone regeneration. This paper could provide empirical bases of MSC-exo-based therapy for bone regeneration and theoretical bases of MSC-exo-induced osteogenesis mechanism. The BMSC-OI-exo-loaded MBG scaffold developed here represented a promising bone repairing strategy for future clinical application." @default.
- W3152258907 created "2021-04-13" @default.
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- W3152258907 date "2021-05-01" @default.
- W3152258907 modified "2023-10-17" @default.
- W3152258907 title "Optimized BMSC-derived osteoinductive exosomes immobilized in hierarchical scaffold via lyophilization for bone repair through Bmpr2/Acvr2b competitive receptor-activated Smad pathway" @default.
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- W3152258907 doi "https://doi.org/10.1016/j.biomaterials.2021.120718" @default.
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