miR-423-5p-enriched small extracellular vesicles drive periodontal regeneration via Sfrp2+ cell expansion

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Small extracellular vesicles (sEVs) show therapeutic potential for periodontitis but functional components remain unclear, limiting clinical periodontal therapy application. Identifying key bioactive molecules and enhancing their functions via engineering strategies may overcome these limitations. By comparing the periodontal tropism of sEVs from different stem cells and conducting functional miRNA profiling, we identified miR-423-5p as a key component for periodontal ligament cell (PDLC) osteogenic differentiation by targeting PLCB1 (Phospholipase C Beta 1). We engineered miR-423-5p-enriched sEVs (sEVs miR-423-5p ) with miRNA loading levels up to 100,000-fold higher than those of native sEVs. Compared with unmodified sEVs, sEVs miR-423-5p promoted the formation of Sfrp2 + osteogenic fibroblasts at periodontal defect sites, ultimately facilitating early osteogenesis and regeneration of a native-like cementum-PDL-alveolar bone complex. These findings establish miR-423-5p as a pivotal osteoinductive effector in sEVs and demonstrate that its targeted enrichment markedly amplifies the regenerative capacity of sEVs, laying the groundwork for personalized nanovesicle-based regenerative therapies.

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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