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Sr-Containing Mesoporous Bioactive Glasses Bio-Functionalized with Recombinant ICOS-Fc: An In Vitro Study

Osteoporotic bone fractures represent a critical clinical issue and require personalized and specific treatments in order to stimulate compromised bone tissue regeneration. In this clinical context, the development of smart nano-biomaterials able to synergistically combine chemical and biological cu...

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Autores principales: Fiorilli, Sonia, Pagani, Mattia, Boggio, Elena, Gigliotti, Casimiro Luca, Dianzani, Chiara, Gauthier, Rémy, Pontremoli, Carlotta, Montalbano, Giorgia, Dianzani, Umberto, Vitale-Brovarone, Chiara
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7911784/
https://www.ncbi.nlm.nih.gov/pubmed/33513769
http://dx.doi.org/10.3390/nano11020321
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author Fiorilli, Sonia
Pagani, Mattia
Boggio, Elena
Gigliotti, Casimiro Luca
Dianzani, Chiara
Gauthier, Rémy
Pontremoli, Carlotta
Montalbano, Giorgia
Dianzani, Umberto
Vitale-Brovarone, Chiara
author_facet Fiorilli, Sonia
Pagani, Mattia
Boggio, Elena
Gigliotti, Casimiro Luca
Dianzani, Chiara
Gauthier, Rémy
Pontremoli, Carlotta
Montalbano, Giorgia
Dianzani, Umberto
Vitale-Brovarone, Chiara
author_sort Fiorilli, Sonia
collection PubMed
description Osteoporotic bone fractures represent a critical clinical issue and require personalized and specific treatments in order to stimulate compromised bone tissue regeneration. In this clinical context, the development of smart nano-biomaterials able to synergistically combine chemical and biological cues to exert specific therapeutic effects (i.e., pro-osteogenic, anti-clastogenic) can allow the design of effective medical solutions. With this aim, in this work, strontium-containing mesoporous bioactive glasses (MBGs) were bio-functionalized with ICOS-Fc, a molecule able to reversibly inhibit osteoclast activity by binding the respective ligand (ICOS-L) and to induce a decrease of bone resorption activity. N(2) adsorption analysis and FT-IR spectroscopy were used to assess the successful grafting of ICOS-Fc on the surface of Sr-containing MBGs, which were also proved to retain the peculiar ability to release osteogenic strontium ions and an excellent bioactivity after functionalization. An ELISA-like assay allowed to confirm that grafted ICOS-Fc molecules were able to bind ICOS-L (the ICOS binding ligand) and to investigate the stability of the amide binding to hydrolysis in aqueous environment up to 21 days. In analogy to the free form of the molecule, the inhibitory effect of grafted ICOS-Fc on cell migratory activity was demonstrated by using ICOSL positive cell lines and the ability to inhibit osteoclast differentiation and function was confirmed by monitoring the differentiation of monocyte-derived osteoclasts (MDOCs), which revealed a strong inhibitory effect, also proven by the downregulation of osteoclast differentiation genes. The obtained results showed that the combination of ICOS-Fc with the intrinsic properties of Sr-containing MBGs represents a very promising approach to design personalized solutions for patients affected by compromised bone remodeling (i.e., osteoporosis fractures).
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spelling pubmed-79117842021-02-28 Sr-Containing Mesoporous Bioactive Glasses Bio-Functionalized with Recombinant ICOS-Fc: An In Vitro Study Fiorilli, Sonia Pagani, Mattia Boggio, Elena Gigliotti, Casimiro Luca Dianzani, Chiara Gauthier, Rémy Pontremoli, Carlotta Montalbano, Giorgia Dianzani, Umberto Vitale-Brovarone, Chiara Nanomaterials (Basel) Article Osteoporotic bone fractures represent a critical clinical issue and require personalized and specific treatments in order to stimulate compromised bone tissue regeneration. In this clinical context, the development of smart nano-biomaterials able to synergistically combine chemical and biological cues to exert specific therapeutic effects (i.e., pro-osteogenic, anti-clastogenic) can allow the design of effective medical solutions. With this aim, in this work, strontium-containing mesoporous bioactive glasses (MBGs) were bio-functionalized with ICOS-Fc, a molecule able to reversibly inhibit osteoclast activity by binding the respective ligand (ICOS-L) and to induce a decrease of bone resorption activity. N(2) adsorption analysis and FT-IR spectroscopy were used to assess the successful grafting of ICOS-Fc on the surface of Sr-containing MBGs, which were also proved to retain the peculiar ability to release osteogenic strontium ions and an excellent bioactivity after functionalization. An ELISA-like assay allowed to confirm that grafted ICOS-Fc molecules were able to bind ICOS-L (the ICOS binding ligand) and to investigate the stability of the amide binding to hydrolysis in aqueous environment up to 21 days. In analogy to the free form of the molecule, the inhibitory effect of grafted ICOS-Fc on cell migratory activity was demonstrated by using ICOSL positive cell lines and the ability to inhibit osteoclast differentiation and function was confirmed by monitoring the differentiation of monocyte-derived osteoclasts (MDOCs), which revealed a strong inhibitory effect, also proven by the downregulation of osteoclast differentiation genes. The obtained results showed that the combination of ICOS-Fc with the intrinsic properties of Sr-containing MBGs represents a very promising approach to design personalized solutions for patients affected by compromised bone remodeling (i.e., osteoporosis fractures). MDPI 2021-01-27 /pmc/articles/PMC7911784/ /pubmed/33513769 http://dx.doi.org/10.3390/nano11020321 Text en © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Fiorilli, Sonia
Pagani, Mattia
Boggio, Elena
Gigliotti, Casimiro Luca
Dianzani, Chiara
Gauthier, Rémy
Pontremoli, Carlotta
Montalbano, Giorgia
Dianzani, Umberto
Vitale-Brovarone, Chiara
Sr-Containing Mesoporous Bioactive Glasses Bio-Functionalized with Recombinant ICOS-Fc: An In Vitro Study
title Sr-Containing Mesoporous Bioactive Glasses Bio-Functionalized with Recombinant ICOS-Fc: An In Vitro Study
title_full Sr-Containing Mesoporous Bioactive Glasses Bio-Functionalized with Recombinant ICOS-Fc: An In Vitro Study
title_fullStr Sr-Containing Mesoporous Bioactive Glasses Bio-Functionalized with Recombinant ICOS-Fc: An In Vitro Study
title_full_unstemmed Sr-Containing Mesoporous Bioactive Glasses Bio-Functionalized with Recombinant ICOS-Fc: An In Vitro Study
title_short Sr-Containing Mesoporous Bioactive Glasses Bio-Functionalized with Recombinant ICOS-Fc: An In Vitro Study
title_sort sr-containing mesoporous bioactive glasses bio-functionalized with recombinant icos-fc: an in vitro study
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7911784/
https://www.ncbi.nlm.nih.gov/pubmed/33513769
http://dx.doi.org/10.3390/nano11020321
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