ArticleMaterials today. Bio2026
Graphene oxide-induced multiple iPSC spheroid formation for enhanced production of angiogenic exosomes accelerating tissue regeneration.
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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6 authors.
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Abstract
Exosome-based therapeutics have emerged as a promising cell-free strategy for tissue regeneration by coordinating angiogenesis and tissue repair. Induced pluripotent stem cell (iPSC)-derived exosomes are particularly attractive because of their regenerative potential and scalability; however, the reproducible and scalable production of functionally potent exosomes remains a major barrier to clinical translation. Here, we developed a graphene oxide (GO)-mediated nanoengineering strategy to establish a multi-spheroid platform that simultaneously regulates spheroid architecture, enhances exosome production, and improves angiogenic functionality in both iPSC spheroids and iPSC-derived vascular endothelial cell (vEC) spheroids. GO reproducibly reorganized cellular aggregation from a single dominant spheroid into multiple uniformly sized spheroids per well and increased exosome production while preserving characteristic vesicle properties. GO-engineered iPSC spheroid-derived exosomes exhibited distinct angiogenesis-related miRNA profiles and significantly enhanced endothelial cell migration and capillary-like network formation in vitro. Extending this strategy to iPSC-vEC spheroids further enhanced endothelial differentiation and generated lineage-specific exosomes with greater pro-angiogenic activity. In a rat full-thickness skin wound model, GO-engineered spheroid-derived exosomes accelerated wound closure and promoted vascularized skin regeneration. Collectively, these findings establish GO-mediated spheroid nanoengineering as a reproducible and potentially scalable strategy for producing therapeutically potent exosomes. By integrating controlled spheroid formation, enhanced exosome productivity, preserved vesicle characteristics, and improved angiogenic efficacy, this platform provides a practical framework for standardized exosome manufacturing and supports its future clinical translation toward vascular regenerative therapies.
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