Graphene oxide-induced multiple iPSC spheroid formation for enhanced production of angiogenic exosomes accelerating tissue regeneration.
4 affiliations
- 1Department of Convergence Biosystems Engineering, Chonnam National University, Gwangju, 61186, Republic of Korea.
- 2Department of Rural and Biosystems Engineering, Chonnam National University, Gwangju, 61186, Republic of Korea.
- 3Interdisciplinary Program in IT-Bio Convergence System, Chonnam National University, Gwangju, 61186, Republic of Korea.
- 4Institute of Nano-Stem Cells Therapeutics, NANOBIOSYSTEM Co., Ltd., Gwangju, 61003, Republic of Korea.
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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BibTeX
@article{kim2026graphene,
title = {{Graphene oxide-induced multiple iPSC spheroid formation for enhanced production of angiogenic exosomes accelerating tissue regeneration.}},
author = {Woochan Kim and Harshita Sharma and Dream Kim and Shinyull Lee and Sefali Bhakuni and Jangho Kim},
journal = {Materials today. Bio},
year = {2026},
month = oct,
doi = {10.1016/j.mtbio.2026.103723},
url = {https://europepmc.org/article/MED/42903656},
note = {CC BY},
}
RIS
TY - JOUR
TI - Graphene oxide-induced multiple iPSC spheroid formation for enhanced production of angiogenic exosomes accelerating tissue regeneration.
AU - Woochan Kim
AU - Harshita Sharma
AU - Dream Kim
AU - Shinyull Lee
AU - Sefali Bhakuni
AU - Jangho Kim
PY - 2026
DA - 2026/10/05
JO - Materials today. Bio
DO - 10.1016/j.mtbio.2026.103723
UR - https://europepmc.org/article/MED/42903656
AB - 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.
SN - 2590-0064
ER -