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

(1) 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...

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Main Authors: Chiara Gardin, Letizia Ferroni, Yaşar Kemal Erdoğan, Federica Zanotti, Francesco De Francesco, Martina Trentini, Giulia Brunello, Batur Ercan, Barbara Zavan
Format: Article
Language:English
Published: MDPI AG 2021-12-01
Series:Nanomaterials
Subjects:
Online Access:https://www.mdpi.com/2079-4991/11/12/3452
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author Chiara Gardin
Letizia Ferroni
Yaşar Kemal Erdoğan
Federica Zanotti
Francesco De Francesco
Martina Trentini
Giulia Brunello
Batur Ercan
Barbara Zavan
author_facet Chiara Gardin
Letizia Ferroni
Yaşar Kemal Erdoğan
Federica Zanotti
Francesco De Francesco
Martina Trentini
Giulia Brunello
Batur Ercan
Barbara Zavan
author_sort Chiara Gardin
collection DOAJ
description (1) 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) 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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spelling doaj.art-e5270ba097ca4ce8ad23005ef5169fc22023-11-23T09:52:47ZengMDPI AGNanomaterials2079-49912021-12-011112345210.3390/nano11123452Nanostructured Modifications of Titanium Surfaces Improve Vascular Regenerative Properties of Exosomes Derived from Mesenchymal Stem Cells: Preliminary In Vitro ResultsChiara Gardin0Letizia Ferroni1Yaşar Kemal Erdoğan2Federica Zanotti3Francesco De Francesco4Martina Trentini5Giulia Brunello6Batur Ercan7Barbara Zavan8Maria Cecilia Hospital, GVM Care & Research, Cotignola, 48033 Ravenna, ItalyMaria Cecilia Hospital, GVM Care & Research, Cotignola, 48033 Ravenna, ItalyBiomedical Engineering Program, Middle East Technical University, Ankara 06800, TurkeyDepartment of Translational Medicine, University of Ferrara, 44121 Ferrara, ItalyDepartment of Plastic and Reconstructive Surgery-Hand Surgery Unit, Azienda ‘Ospedali Riuniti’, 60126 Ancona, ItalyDepartment of Translational Medicine, University of Ferrara, 44121 Ferrara, ItalyDepartment of Neurosciences, Dentistry Section, University of Padova, 35128 Padova, ItalyBiomedical Engineering Program, Middle East Technical University, Ankara 06800, TurkeyDepartment of Translational Medicine, University of Ferrara, 44121 Ferrara, Italy(1) 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) 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.https://www.mdpi.com/2079-4991/11/12/3452titanium nanotubesendothelializationmesenchymal stem cellsendothelial cellsangiogenesiscardiovascular metal stents
spellingShingle Chiara Gardin
Letizia Ferroni
Yaşar Kemal Erdoğan
Federica Zanotti
Francesco De Francesco
Martina Trentini
Giulia Brunello
Batur Ercan
Barbara Zavan
Nanostructured Modifications of Titanium Surfaces Improve Vascular Regenerative Properties of Exosomes Derived from Mesenchymal Stem Cells: Preliminary In Vitro Results
Nanomaterials
titanium nanotubes
endothelialization
mesenchymal stem cells
endothelial cells
angiogenesis
cardiovascular metal stents
title Nanostructured Modifications of Titanium Surfaces Improve Vascular Regenerative Properties of Exosomes Derived from Mesenchymal Stem Cells: Preliminary In Vitro Results
title_full Nanostructured Modifications of Titanium Surfaces Improve Vascular Regenerative Properties of Exosomes Derived from Mesenchymal Stem Cells: Preliminary In Vitro Results
title_fullStr Nanostructured Modifications of Titanium Surfaces Improve Vascular Regenerative Properties of Exosomes Derived from Mesenchymal Stem Cells: Preliminary In Vitro Results
title_full_unstemmed Nanostructured Modifications of Titanium Surfaces Improve Vascular Regenerative Properties of Exosomes Derived from Mesenchymal Stem Cells: Preliminary In Vitro Results
title_short Nanostructured Modifications of Titanium Surfaces Improve Vascular Regenerative Properties of Exosomes Derived from Mesenchymal Stem Cells: Preliminary In Vitro Results
title_sort nanostructured modifications of titanium surfaces improve vascular regenerative properties of exosomes derived from mesenchymal stem cells preliminary in vitro results
topic titanium nanotubes
endothelialization
mesenchymal stem cells
endothelial cells
angiogenesis
cardiovascular metal stents
url https://www.mdpi.com/2079-4991/11/12/3452
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