Journal
CHEMICAL ENGINEERING JOURNAL
Volume 471, Issue -, Pages -Publisher
ELSEVIER SCIENCE SA
DOI: 10.1016/j.cej.2023.144594
Keywords
MSCs; Exosomes; miR-26a; Osteoporosis; Bone targeting; Bone regeneration
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This study provides a feasible and effective strategy for modifying engineered exosomes to enhance bone regeneration.
Mesenchymal stem cell-derived exosomes (MSC-Exos) have shown great potential in the areas of bone regen-eration and treatment of age-related diseases. Engineered exosomes can integrate multiple functional compo-nents to achieve optimal, targeted therapeutic effects. This study combined large-scale generation, bone-targeting modification, and miR-26a loading for exosome-mimetics (EMs) to construct a cell-free delivery sys-tem that promotes bone regeneration with good biocompatibility. EMs were fabricated through sequential extrusion of MSCs and reached a 15-fold production yield compared to conventional exosome secretion. Systemic injection of Asp8-EM/miR-26a in mouse models accelerated bone-defect healing and prevented osteoporosis. The underlying mechanism involves miR-26a targeting glycogen synthase kinase-38 (GSK-38) to induce 8-catenin accumulation, thus activating Wnt signaling pathway and promoting bone regeneration. This study provides a feasible and effective strategy for modifying EMs to enhance bone regeneration.
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