Self-Organizing 3D Dermal Papilla Cell Spheroids Yield Therapeutic Extracellular Vesicles that Target Hypertrophic Scar Regression via the miR-26a-5p/CCNE2 Axis

    July 2025 in “ Burns & Trauma ”
    Yunwei Wang, Luyang Zhao, Hao Ma, Ao Shi, Peng Cao, Feiyu Cai, Ruomei Zhao, Gang Wang, Zhihan Hu, Jiatong Wang, Yuchen Kang, Xiaoyu Di, Qingyi Zhang, Hao Zhang, Shuguang Hou, Babo Zhang, Han Wang, Yi Liu, Hao Guan
    TLDR 3D cell spheroids can help reduce scars by delivering therapeutic vesicles.
    This study demonstrates that self-organizing 3D dermal papilla cell spheroids (tdDPCs) can produce extracellular vesicles (EVs) with therapeutic potential for hypertrophic scar regression. Using a novel SFL-3D platform, tdDPCs were expanded and maintained high viability, overcoming limitations of traditional cultures. The tdDPC-derived EVs, enriched with miR-26a-5p, effectively reduced fibrosis by silencing CCNE2 and inhibiting PI3K/AKT-driven collagen production, as well as suppressing myofibroblast differentiation. In a rabbit ear model, these EVs significantly improved scar characteristics, suggesting their potential as a scalable, acellular therapy for hypertrophic scar management.
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