Self-Organizing 3D Culture–Derived Extracellular Vesicles Suppress Hypertrophic Scarring via the miR-26a-5p–CCNE2 Axis. (IMAGE)

Burns & Trauma

Self-Organizing 3D Culture–Derived Extracellular Vesicles Suppress Hypertrophic Scarring via the miR-26a-5p–CCNE2 Axis.

Caption

Self-Organizing 3D Culture–Derived Extracellular Vesicles Suppress Hypertrophic Scarring via the miR-26a-5p–CCNE2 Axis. Schematic illustration of the therapeutic mechanism by which self-feeder layer three-dimensional (SFL-3D) culture–derived dermal papilla cell extracellular vesicles (tdDPC-EVs) attenuate hypertrophic scarring. Dermal papilla cells isolated from hair follicles are reprogrammed into self-organizing spheroids using the SFL-3D culture system, enabling sustained production of tdDPC-EVs enriched in miR-26a-5p. Following local injection in a rabbit ear hypertrophic scar model, tdDPC-EVs are internalized by hypertrophic scar–derived fibroblasts (HSFs), where vesicle-delivered miR-26a-5p suppresses CCNE2 expression via the RNA-induced silencing complex (RISC). Downregulation of CCNE2 inhibits PI3K/AKT signaling, reduces α-smooth muscle actin (α-SMA) and collagen I expression, and ultimately limits fibroblast hyperactivation and pathological matrix deposition, promoting scar regression and scarless skin repair.

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Burns & Trauma

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