Nanostructured Modifications of Titanium Surfaces Improve Vascular Regenerative Properties of Exosomes Derived from Mesenchymal Stem Cells: Preliminary In Vitro Results

钛表面的纳米结构修饰可改善间充质干细胞外泌体的血管再生特性:初步体外结果

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作者:Chiara Gardin, Letizia Ferroni, Yaşar Kemal Erdoğan, Federica Zanotti, Francesco De Francesco, Martina Trentini, Giulia Brunello, Batur Ercan, Barbara Zavan

Background

Implantation of metal-based scaffolds is a common procedure for treating several diseases. However, the success of the long-term application is limited by an insufficient endothelialization of the material surface. Nanostructured modifications of metal scaffolds represent a promising approach to faster biomaterial osteointegration through increasing of endothelial commitment of the mesenchymal stem cells (MSC). (2)

Conclusions

Preconditioning of hMSCs on TNs induced elevated exosomes secretion that stimulated in vitro endothelial and cell activity, which might improve in vivo angiogenesis, supporting faster scaffold integration.

Methods

Three different nanotubular Ti surfaces (TNs manufactured by electrochemical anodization with diameters of 25, 80, or 140 nm) were seeded with human MSCs (hMSCs) and their exosomes were isolated and tested with human umbilical vein endothelial cells (HUVECs) to assess whether TNs can influence the secretory functions of hMSCs and whether these in turn affect endothelial and osteogenic cell activities in vitro. (3)

Results

The hMSCs adhered on all TNs and significantly expressed angiogenic-related factors after 7 days of culture when compared to untreated Ti substrates. Nanomodifications of Ti surfaces significantly improved the release of hMSCs exosomes, having dimensions below 100 nm and expressing CD63 and CD81 surface markers. These hMSC-derived exosomes were efficiently internalized by HUVECs, promoting their migration and differentiation. In addition, they selectively released a panel of miRNAs directly or indirectly related to angiogenesis. (4) Conclusions: Preconditioning of hMSCs on TNs induced elevated exosomes secretion that stimulated in vitro endothelial and cell activity, which might improve in vivo angiogenesis, supporting faster scaffold integration.

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