Nano-vibration exciter: Hypoxia-inducible factor 1 signaling pathway-mediated extracellular vesicles as bioactive glass substitutes for bone regeneration

• Published in: Bioactive materials Vol. 40; pp. 460 - 473
• Main Authors: Wang, Zetao, Dai, Qiyuan, Luo, Huitong, Han, Xiyuan, Feng, Qi, Cao, Xiaodong
• Format: Journal Article
• Language: English
• Published: China Elsevier B.V 01-10-2024; KeAi Publishing Communications Ltd; KeAi Communications Co., Ltd
• Subjects: Angiogenesis; Apoptosis; Autophagy; Biocompatibility; Bioglass; Biological activity; Biological products; Bone growth; Bone healing; Bone regeneration; Copper; Copper converters; Copper-doped bioactive glass; Cytotoxicity; Extracellular vesicles; HIF-1α; Hypoxia; Hypoxia-inducible factor 1; Long bone; Mesenchymal stem cells; Metal ions; MicroRNAs; Nanoparticles; Osteogenesis; Regeneration; Regeneration (physiology); Signal transduction; Stem cells; Tissue engineering; Trauma; Vascular endothelial growth factor; Vascularization; Vesicles; Vibration; Copper-doped bioactive glass; Extracellular vesicles; HIF-1α; Bone regeneration
• ISSN: 2452-199X; 2097-1192; 2452-199X
• DOI: 10.1016/j.bioactmat.2024.06.023

Bioactive glasses (BG) play a vital role in angiogenesis and osteogenesis through releasing functional ions. However, the rapid ion release in the early stage will cause excessive accumulation of metal ions, which in turn leads to obvious cytotoxicity, long-term inflammation, and bone repair failure. Inspired by the vibration exciter, small extracellular vesicles (sEVs) obtained by treating mesenchymal stem cells with copper-doped bioactive glass (CuBG-sEVs), is prepared as a nano-vibration exciter. The nano-vibration exciter can convert the ion signals of CuBG into biochemical factor signals through hypoxia-inducible factor 1 (HIF-1) signaling pathway and its activated autophagy, so as to better exert the osteogenic activity of BG. The results showed that CuBG extracts could significantly improve the enrichment of key miRNAs and increase the yield of CuBG-sEVs by activating HIF-1 signaling pathway and its activated autophagy. Cell experiments showed that CuBG-sEVs are favor to cell recruitment, vascularization and osteogenesis as the enrichment of key miRNAs. The animal experiments results showed that CuBG-sEVs stimulated angiogenesis mediated by CD31 and promoted bone regeneration by activating signaling pathways related to osteogenesis. These findings underscored the significant potential of sEVs as alternative strategies to better roles of BG.
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•The CuBG stimulates BMSCs to increase sEVs activity and yields.•The activation of HIF-1 signaling pathway by CuBG increases miR-210 content in sEVs.•The CuBG-sEVs promote vascularized bone regeneration.