Exosome has been considered as an instructive supplement between complicated cell therapy and single gene/protein drug treatment in the field of regenerative medicine due to its excellent biocompatibility, efficient cellular internalization and large loading capacity. Nevertheless, one major issue that extremely restricts the potential application as gene/drug vehicles is the low yield of nanoscale exosome. Moreover, the intravenous injection of targeted exosomes may cause the obstruction of blood-rich organs. Thus, herein we fabricated a specific exosome-mimetics (EM) that can come true mass and fast production exhibits the similar size, morphology and membrane protein markers in comparison with conventional exosomes. To bypass the risk of intravenous injection and improve the efficiency of topical therapy, we simultaneously applied the engineered EM to design a gene-activated matrix (GAM) that could be locally released by encapsulating the plasmid of vascular endothelial growth factor (VEGF) and flexibly binding onto a core-shell nanofiber film. Our findings showed that the well-designed engineered EM-mediated GAM was able to sustainably deliver VEGF gene and significantly enhance the vascularized osteogenesis in vivo. The current work can not only consolidate the applied foundation of EMs through the breakthrough of high yield, but also provides a local and effective delivery of engineered EMs for the in-situ therapy.

外来体由于其优异的生物相容性，有效的细胞内在化和大的负载能力，在再生医学领域被认为是复杂细胞疗法和单基因/蛋白质药物治疗之间的有益指导。然而，作为基因/药物载体，极大地限制了其潜在应用的一个主要问题是纳米级外泌体的产量低。此外，静脉注射靶向的外来体可能会阻塞血液丰富的器官。因此，本文中我们制造了一种特定的外泌体模拟物（EM），它可以实现大规模生产，并且与常规外泌体相比，快速生产显示出相似的大小，形态和膜蛋白标记。为了绕过静脉注射的风险并提高局部治疗的效率，我们同时应用工程化的EM设计了一个基因激活基质（GAM），该基因可以通过包裹血管内皮生长因子（VEGF）的质粒并灵活结合到核-壳纳米纤维膜上而局部释放。我们的研究结果表明，精心设计的工程化EM介导的GAM能够持续递送VEGF基因，并显着增强体内血管化成骨作用。当前的工作不仅可以通过高产率的突破来巩固EM的应用基础，而且可以为局部治疗提供局部有效的工程化EM交付。我们的研究结果表明，精心设计的工程化EM介导的GAM能够持续递送VEGF基因，并显着增强体内血管化成骨作用。当前的工作不仅可以通过高产率的突破来巩固EM的应用基础，而且可以为局部治疗提供局部有效的工程化EM交付。我们的研究结果表明，精心设计的工程化EM介导的GAM能够持续递送VEGF基因，并显着增强体内血管化成骨作用。当前的工作不仅可以通过高产率的突破来巩固EM的应用基础，而且可以为局部治疗提供局部有效的工程化EM交付。