The Implication of Spatial Statistics in Human Mesenchymal Stem Cell Response to Nanotubular Architectures

Alexander J Steeves,1,2 William Ho,1,2,* Maria Chiara Munisso,3,* David J Lomboni,1,2 Enara Larrañaga,4 Sidney Omelon,1,5 Elena Martínez,4,6,7 Davide Spinello,1 Fabio Variola1,2,8,9 1Faculty of Engineering, Department of Mechanical Engineering, University of Ottawa, Ottawa, ON,...

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Autores principales:	Steeves AJ, Ho W, Munisso MC, Lomboni DJ, Larrañaga E, Omelon S, Martínez E, Spinello D, Variola F
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2020
Materias:	nanotubes nanotopography spatial statistics stem cells bone quality Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/c94f2adfb8c04dd388370745157024b6
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id	oai:doaj.org-article:c94f2adfb8c04dd388370745157024b6
record_format	dspace
institution	DOAJ
collection	DOAJ
language	EN
topic	nanotubes nanotopography spatial statistics stem cells bone quality Medicine (General) R5-920
spellingShingle	nanotubes nanotopography spatial statistics stem cells bone quality Medicine (General) R5-920 Steeves AJ Ho W Munisso MC Lomboni DJ Larrañaga E Omelon S Martínez E Spinello D Variola F The Implication of Spatial Statistics in Human Mesenchymal Stem Cell Response to Nanotubular Architectures
description	Alexander J Steeves,1,2 William Ho,1,2,* Maria Chiara Munisso,3,* David J Lomboni,1,2 Enara Larrañaga,4 Sidney Omelon,1,5 Elena Martínez,4,6,7 Davide Spinello,1 Fabio Variola1,2,8,9 1Faculty of Engineering, Department of Mechanical Engineering, University of Ottawa, Ottawa, ON, Canada; 2Ottawa-Carleton Institute for Biomedical Engineering, Ottawa, Canada; 3Department of Plastic and Reconstructive Surgery, Kansai Medical University, Moriguchi, Japan; 4Institute for Bioengineering of Catalonia (IBEC), The Barcelona Institute of Science and Technology (BIST), Barcelona, Spain; 5Faculty of Engineering, Department of Mining and Materials Engineering, McGill University, Montreal, QC, Canada; 6Centro de Investigación Biomédica en Red (CIBER), Madrid, Spain; 7Department of Electronics and Biomedical Engineering, University of Barcelona, Barcelona, Spain; 8Faculty of Medicine, Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, ON, Canada; 9Children’s Hospital of Eastern Ontario (CHEO), Ottawa, ON, Canada*These authors contributed equally to this workCorrespondence: Fabio Variola Email fabio.variola@uottawa.caIntroduction: In recent years there has been ample interest in nanoscale modifications of synthetic biomaterials to understand fundamental aspects of cell-surface interactions towards improved biological outcomes. In this study, we aimed at closing in on the effects of nanotubular TiO2 surfaces with variable nanotopography on the response on human mesenchymal stem cells (hMSCs). Although the influence of TiO2 nanotubes on the cellular response, and in particular on hMSC activity, has already been addressed in the past, previous studies overlooked critical morphological, structural and physical aspects that go beyond the simple nanotube diameter, such as spatial statistics.Methods: To bridge this gap, we implemented an extensive characterization of nanotubular surfaces generated by anodization of titanium with a focus on spatial structural variables including eccentricity, nearest neighbour distance (NND) and Voronoi entropy, and associated them to the hMSC response. In addition, we assessed the biological potential of a two-tiered honeycomb nanoarchitecture, which allowed the detection of combinatory effects that this hierarchical structure has on stem cells with respect to conventional nanotubular designs. We have combined experimental techniques, ranging from Scanning Electron (SEM) and Atomic Force (AFM) microscopy to Raman spectroscopy, with computational simulations to characterize and model nanotubular surfaces. We evaluated the cell response at 6 hrs, 1 and 2 days by fluorescence microscopy, as well as bone mineral deposition by Raman spectroscopy, demonstrating substrate-induced differential biological cueing at both the short- and long-term.Results: Our work demonstrates that the nanotube diameter is not sufficient to comprehensively characterize nanotubular surfaces and equally important parameters, such as eccentricity and wall thickness, ought to be included since they all contribute to the overall spatial disorder which, in turn, dictates the overall bioactive potential. We have also demonstrated that nanotubular surfaces affect the quality of bone mineral deposited by differentiated stem cells. Lastly, we closed in on the integrated effects exerted by the superimposition of two dissimilar nanotubular arrays in the honeycomb architecture.Discussion: This work delineates a novel approach for the characterization of TiO2 nanotubes which supports the incorporation of critical spatial structural aspects that have been overlooked in previous research. This is a crucial aspect to interpret cellular behaviour on nanotubular substrates. Consequently, we anticipate that this strategy will contribute to the unification of studies focused on the use of such powerful nanostructured surfaces not only for biomedical applications but also in other technology fields, such as catalysis.Keywords: nanotubes, nanotopography, spatial statistics, stem cells, bone quality
format	article
author	Steeves AJ Ho W Munisso MC Lomboni DJ Larrañaga E Omelon S Martínez E Spinello D Variola F
author_facet	Steeves AJ Ho W Munisso MC Lomboni DJ Larrañaga E Omelon S Martínez E Spinello D Variola F
author_sort	Steeves AJ
title	The Implication of Spatial Statistics in Human Mesenchymal Stem Cell Response to Nanotubular Architectures
title_short	The Implication of Spatial Statistics in Human Mesenchymal Stem Cell Response to Nanotubular Architectures
title_full	The Implication of Spatial Statistics in Human Mesenchymal Stem Cell Response to Nanotubular Architectures
title_fullStr	The Implication of Spatial Statistics in Human Mesenchymal Stem Cell Response to Nanotubular Architectures
title_full_unstemmed	The Implication of Spatial Statistics in Human Mesenchymal Stem Cell Response to Nanotubular Architectures
title_sort	implication of spatial statistics in human mesenchymal stem cell response to nanotubular architectures
publisher	Dove Medical Press
publishDate	2020
url	https://doaj.org/article/c94f2adfb8c04dd388370745157024b6
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spelling	oai:doaj.org-article:c94f2adfb8c04dd388370745157024b62021-12-02T08:48:12ZThe Implication of Spatial Statistics in Human Mesenchymal Stem Cell Response to Nanotubular Architectures1178-2013https://doaj.org/article/c94f2adfb8c04dd388370745157024b62020-03-01T00:00:00Zhttps://www.dovepress.com/the-implication-of-spatial-statistics-in-human-mesenchymal-stem-cell-r-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Alexander J Steeves,1,2 William Ho,1,2,* Maria Chiara Munisso,3,* David J Lomboni,1,2 Enara Larrañaga,4 Sidney Omelon,1,5 Elena Martínez,4,6,7 Davide Spinello,1 Fabio Variola1,2,8,9 1Faculty of Engineering, Department of Mechanical Engineering, University of Ottawa, Ottawa, ON, Canada; 2Ottawa-Carleton Institute for Biomedical Engineering, Ottawa, Canada; 3Department of Plastic and Reconstructive Surgery, Kansai Medical University, Moriguchi, Japan; 4Institute for Bioengineering of Catalonia (IBEC), The Barcelona Institute of Science and Technology (BIST), Barcelona, Spain; 5Faculty of Engineering, Department of Mining and Materials Engineering, McGill University, Montreal, QC, Canada; 6Centro de Investigación Biomédica en Red (CIBER), Madrid, Spain; 7Department of Electronics and Biomedical Engineering, University of Barcelona, Barcelona, Spain; 8Faculty of Medicine, Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, ON, Canada; 9Children’s Hospital of Eastern Ontario (CHEO), Ottawa, ON, Canada*These authors contributed equally to this workCorrespondence: Fabio Variola Email fabio.variola@uottawa.caIntroduction: In recent years there has been ample interest in nanoscale modifications of synthetic biomaterials to understand fundamental aspects of cell-surface interactions towards improved biological outcomes. In this study, we aimed at closing in on the effects of nanotubular TiO2 surfaces with variable nanotopography on the response on human mesenchymal stem cells (hMSCs). Although the influence of TiO2 nanotubes on the cellular response, and in particular on hMSC activity, has already been addressed in the past, previous studies overlooked critical morphological, structural and physical aspects that go beyond the simple nanotube diameter, such as spatial statistics.Methods: To bridge this gap, we implemented an extensive characterization of nanotubular surfaces generated by anodization of titanium with a focus on spatial structural variables including eccentricity, nearest neighbour distance (NND) and Voronoi entropy, and associated them to the hMSC response. In addition, we assessed the biological potential of a two-tiered honeycomb nanoarchitecture, which allowed the detection of combinatory effects that this hierarchical structure has on stem cells with respect to conventional nanotubular designs. We have combined experimental techniques, ranging from Scanning Electron (SEM) and Atomic Force (AFM) microscopy to Raman spectroscopy, with computational simulations to characterize and model nanotubular surfaces. We evaluated the cell response at 6 hrs, 1 and 2 days by fluorescence microscopy, as well as bone mineral deposition by Raman spectroscopy, demonstrating substrate-induced differential biological cueing at both the short- and long-term.Results: Our work demonstrates that the nanotube diameter is not sufficient to comprehensively characterize nanotubular surfaces and equally important parameters, such as eccentricity and wall thickness, ought to be included since they all contribute to the overall spatial disorder which, in turn, dictates the overall bioactive potential. We have also demonstrated that nanotubular surfaces affect the quality of bone mineral deposited by differentiated stem cells. Lastly, we closed in on the integrated effects exerted by the superimposition of two dissimilar nanotubular arrays in the honeycomb architecture.Discussion: This work delineates a novel approach for the characterization of TiO2 nanotubes which supports the incorporation of critical spatial structural aspects that have been overlooked in previous research. This is a crucial aspect to interpret cellular behaviour on nanotubular substrates. Consequently, we anticipate that this strategy will contribute to the unification of studies focused on the use of such powerful nanostructured surfaces not only for biomedical applications but also in other technology fields, such as catalysis.Keywords: nanotubes, nanotopography, spatial statistics, stem cells, bone qualitySteeves AJHo WMunisso MCLomboni DJLarrañaga EOmelon SMartínez ESpinello DVariola FDove Medical Pressarticlenanotubesnanotopographyspatial statisticsstem cellsbone qualityMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 15, Pp 2151-2169 (2020)

The Implication of Spatial Statistics in Human Mesenchymal Stem Cell Response to Nanotubular Architectures

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