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Arginine-glycine-aspartic acid (RGD) dendrimer-based nanopatterns on poly(L-lactic acid) were used as bioactive substrates to evaluate the impact of the RGD local surface density on the chondrogenic induction of adult human mesenchymal stem cells. During chondrogenic commitment, active extracellular matrix (ECM) remodeling takes place, playing an instructive role in the differentiation process. Although three-dimensional environments such as pellet or micromass cultures are commonly used for in vitro chondrogenic differentiation, these cultures are rather limited with respect to their ability to interrogate cells in cell–ECM interactions. In the present study, the nanopatterns of the tunable RGD surface density were obtained as a function of the initial dendrimer concentration. The local RGD surface density was quantified through probability contour plots for the minimum interparticle distance, constructed from the corresponding atomic force microscopy images, and correlated with the cell adhesion and differentiation response. The results revealed that the local RGD surface density at the nanoscale acts as a regulator of chondrogenic commitment, and that intermediate adhesiveness of cells to the substrates favors mesenchymal cell condensation and early chondrogenic differentiation.


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Tailoring RGD local surface density at the nanoscale toward adult stem cell chondrogenic commitment

Show Author's information Anna Lagunas1,2( )Iro Tsintzou2Yolanda Vida3,4Daniel Collado3,4Ezequiel Pérez-Inestrosa3,4Cristina Rodríguez Pereira5Joana Magalhaes1,5José A. Andrades6,1Josep Samitier2,1,7
Networking Biomedical Research Center (CIBER)C/ Monforte de Lemos 3-5Pabellón 11 Planta 0Madrid28029Spain
Institute for Bioengineering of Catalonia (IBEC)Baldiri-Reixac 10-12Barcelona08028Spain
Instituto de Investigación Biomédica de Málaga (IBIMA)Department of Organic ChemistryUniversidad de Málaga (UMA)Málaga29071Spain
Andalusian Centre for Nanomedicine and Biotechnology-BIONANDParque Tecnológico de AndalucíaMálaga29590Spain
Unidad de Bioingeniería Tisular y Terapia Celular (GBTTC-CHUAC)Grupo de ReumatologíaInstituto de Investigación Biomédica de A Coruña (INIBIC)Complexo Hospitalario Universitario de A Coruña (CHUAC)Sergas, Universidade da Coruña (UDC), As Xubias, 84Coruña15006Spain
Cell BiologyGenetics and Physiology DepartmentUniversity de Málaga (UMA)Campus TeatinosMálaga29071Spain
Department of Engineering ElectronicsUniversity of Barcelona (UB)Martí i Franquès 1-11Barcelona08028Spain

Abstract

Arginine-glycine-aspartic acid (RGD) dendrimer-based nanopatterns on poly(L-lactic acid) were used as bioactive substrates to evaluate the impact of the RGD local surface density on the chondrogenic induction of adult human mesenchymal stem cells. During chondrogenic commitment, active extracellular matrix (ECM) remodeling takes place, playing an instructive role in the differentiation process. Although three-dimensional environments such as pellet or micromass cultures are commonly used for in vitro chondrogenic differentiation, these cultures are rather limited with respect to their ability to interrogate cells in cell–ECM interactions. In the present study, the nanopatterns of the tunable RGD surface density were obtained as a function of the initial dendrimer concentration. The local RGD surface density was quantified through probability contour plots for the minimum interparticle distance, constructed from the corresponding atomic force microscopy images, and correlated with the cell adhesion and differentiation response. The results revealed that the local RGD surface density at the nanoscale acts as a regulator of chondrogenic commitment, and that intermediate adhesiveness of cells to the substrates favors mesenchymal cell condensation and early chondrogenic differentiation.

Keywords: dendrimer, nanopattern, arginine-glycine-aspartic acid (RGD), human mesenchymal stem cells (hMSCs), chondrogenesis

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Publication history
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Acknowledgements

Publication history

Received: 14 June 2016
Revised: 17 November 2016
Accepted: 21 November 2016
Published: 29 December 2016
Issue date: June 2017

Copyright

© Tsinghua University Press and Springer-Verlag Berlin Heidelberg 2016

Acknowledgements

Acknowledgements

Authors acknowledge Prof. Pau Gorostiza for its help in STM experiments, Albert G. Castaño for his help in dmin quantification, and Dr. David Caballero for his support in microscopy video recording. This work was supported by Networking Biomedical Research Center (CIBER), Spain. CIBER is an initiative funded by the Ⅵ National R & D & i Plan 2008-2011, Iniciativa Ingenio 2010, Consolider Program, CIBER Actions, and the Instituto de Salud Carlos Ⅲ, with the support of the European Regional Development Fund. This work has been financially supported by the Commission for Universities and Research of the Department of Innovation, Universities, and Enterprise of the Generalitat de Catalunya (2014 SGR 1442). This work was funded by the project OLIGOCODES (No. MAT2012-38573-C02) and by the project CTQ2013-41339-P, awarded by the Spanish Ministry of Economy and Competitiveness. C. R. P. acknowledges financial support from the Spanish Ministry of Economy and Competitiveness grant (No. IFI15/00151).

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