Exosomal mRNAs for Angiogenic–Osteogenic Coupled Bone Repair

Yifan Ma, Lili Sun, Jingjing Zhang, Chi ling Chiang, Junjie Pan, Xinyu Wang, Kwang Joo Kwak, Hong Li, Renliang Zhao, Xilal Y. Rima, Chi Zhang, Anan Zhang, Yutong Liu, Zirui He, Derek Hansford, Eduardo Reategui, Changsheng Liu, Andrew S. Lee, Yuan Yuan*, Ly James Lee*

*此作品的通信作者

研究成果: Article同行評審

20 引文 斯高帕斯(Scopus)

摘要

Regenerative medicine in tissue engineering often relies on stem cells and specific growth factors at a supraphysiological dose. These approaches are costly and may cause severe side effects. Herein, therapeutic small extracellular vesicles (t-sEVs) endogenously loaded with a cocktail of human vascular endothelial growth factor A (VEGF-A) and human bone morphogenetic protein 2 (BMP-2) mRNAs within a customized injectable PEGylated poly (glycerol sebacate) acrylate (PEGS-A) hydrogel for bone regeneration in rats with challenging femur critical-size defects are introduced. Abundant t-sEVs are produced by a facile cellular nanoelectroporation system based on a commercially available track-etched membrane (TM-nanoEP) to deliver plasmid DNAs to human adipose-derived mesenchymal stem cells (hAdMSCs). Upregulated microRNAs associated with the therapeutic mRNAs are enriched in t-sEVs for enhanced angiogenic–osteogenic regeneration. Localized and controlled release of t-sEVs within the PEGS-A hydrogel leads to the retention of therapeutics in the defect site for highly efficient bone regeneration with minimal low accumulation in other organs.

原文English
文章編號2302622
期刊Advanced Science
10
發行號33
DOIs
出版狀態Published - 24 11月 2023

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