ArticleMaterials today. Bio2026
Skin organoid-derived exosomes in a hydrogel system potentiate skin wound healing.
Article in Materials today. Bio, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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10 authors.
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Abstract
Skin wounds, whether acute or chronic, remain a major clinical challenge due to their complex healing processes involving inflammation, angiogenesis, and tissue remodeling. While stem cell-derived exosomes offer a promising cell-free therapeutic approach, their clinical translation is limited by rapid clearance and insufficient tissue-specificity. In this study, we developed a novel strategy by integrating exosomes derived from skin organoids (SKO-Exo)-which mimic native skin heterogeneity-into a hydrogel-based sustained-release system (Exo-Gel) to enhance wound healing. Skin organoids were generated from human embryonic stem cells, and exosomes were isolated and characterized, revealing typical cup-shaped morphology and exosomal markers. The hydrogel, composed of polyvinyl alcohol/gelatin/boric acid, exhibited excellent self-healing, adhesion, and sustained exosome release with an initial burst. In vitro, SKO-Exo-loaded hydrogel (SKOexo-Gel) significantly promoted endothelial cell proliferation, migration, and tube formation, as well as fibroblast collagen III secretion, outperforming exosomes from 3D keratinocytes (KC-Exo). In a rat full-thickness wound model, SKOexo-Gel accelerated wound closure, enhanced angiogenesis, and increased collagen III deposition. miRNA sequencing identified Hsa-miR-125b-5p as a prominent SKO-Exo-enriched miRNA that activates the Wnt/β-catenin pathway to drive angiogenesis, validated by functional assays. These findings demonstrate that skin organoid-derived exosomes in a hydrogel system synergistically promote wound healing through tissue-specific cues, offering a next-generation therapy for refractory wounds.
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