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Customized bioreactor enables the production of 3D diaphragmatic constructs influencing matrix remodeling and fibroblast overgrowth

The production of skeletal muscle constructs useful for replacing large defects in vivo, such as in congenital diaphragmatic hernia (CDH), is still considered a challenge. The standard application of prosthetic material presents major limitations, such as hernia recurrences in a remarkable number of...

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Autores principales: Maghin, Edoardo, Carraro, Eugenia, Boso, Daniele, Dedja, Arben, Giagante, Mattia, Caccin, Paola, Barna, Raluca Ana-Maria, Bresolin, Silvia, Cani, Alice, Borile, Giulia, Sandrin, Deborah, Romanato, Filippo, Cecchinato, Francesca, Urciuolo, Anna, Sandonà, Dorianna, De Coppi, Paolo, Pavan, Piero G., Piccoli, Martina
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9038738/
https://www.ncbi.nlm.nih.gov/pubmed/35468920
http://dx.doi.org/10.1038/s41536-022-00222-x
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author Maghin, Edoardo
Carraro, Eugenia
Boso, Daniele
Dedja, Arben
Giagante, Mattia
Caccin, Paola
Barna, Raluca Ana-Maria
Bresolin, Silvia
Cani, Alice
Borile, Giulia
Sandrin, Deborah
Romanato, Filippo
Cecchinato, Francesca
Urciuolo, Anna
Sandonà, Dorianna
De Coppi, Paolo
Pavan, Piero G.
Piccoli, Martina
author_facet Maghin, Edoardo
Carraro, Eugenia
Boso, Daniele
Dedja, Arben
Giagante, Mattia
Caccin, Paola
Barna, Raluca Ana-Maria
Bresolin, Silvia
Cani, Alice
Borile, Giulia
Sandrin, Deborah
Romanato, Filippo
Cecchinato, Francesca
Urciuolo, Anna
Sandonà, Dorianna
De Coppi, Paolo
Pavan, Piero G.
Piccoli, Martina
author_sort Maghin, Edoardo
collection PubMed
description The production of skeletal muscle constructs useful for replacing large defects in vivo, such as in congenital diaphragmatic hernia (CDH), is still considered a challenge. The standard application of prosthetic material presents major limitations, such as hernia recurrences in a remarkable number of CDH patients. With this work, we developed a tissue engineering approach based on decellularized diaphragmatic muscle and human cells for the in vitro generation of diaphragmatic-like tissues as a proof-of-concept of a new option for the surgical treatment of large diaphragm defects. A customized bioreactor for diaphragmatic muscle was designed to control mechanical stimulation and promote radial stretching during the construct engineering. In vitro tests demonstrated that both ECM remodeling and fibroblast overgrowth were positively influenced by the bioreactor culture. Mechanically stimulated constructs also increased tissue maturation, with the formation of new oriented and aligned muscle fibers. Moreover, after in vivo orthotopic implantation in a surgical CDH mouse model, mechanically stimulated muscles maintained the presence of human cells within myofibers and hernia recurrence did not occur, suggesting the value of this approach for treating diaphragm defects.
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spelling pubmed-90387382022-04-28 Customized bioreactor enables the production of 3D diaphragmatic constructs influencing matrix remodeling and fibroblast overgrowth Maghin, Edoardo Carraro, Eugenia Boso, Daniele Dedja, Arben Giagante, Mattia Caccin, Paola Barna, Raluca Ana-Maria Bresolin, Silvia Cani, Alice Borile, Giulia Sandrin, Deborah Romanato, Filippo Cecchinato, Francesca Urciuolo, Anna Sandonà, Dorianna De Coppi, Paolo Pavan, Piero G. Piccoli, Martina NPJ Regen Med Article The production of skeletal muscle constructs useful for replacing large defects in vivo, such as in congenital diaphragmatic hernia (CDH), is still considered a challenge. The standard application of prosthetic material presents major limitations, such as hernia recurrences in a remarkable number of CDH patients. With this work, we developed a tissue engineering approach based on decellularized diaphragmatic muscle and human cells for the in vitro generation of diaphragmatic-like tissues as a proof-of-concept of a new option for the surgical treatment of large diaphragm defects. A customized bioreactor for diaphragmatic muscle was designed to control mechanical stimulation and promote radial stretching during the construct engineering. In vitro tests demonstrated that both ECM remodeling and fibroblast overgrowth were positively influenced by the bioreactor culture. Mechanically stimulated constructs also increased tissue maturation, with the formation of new oriented and aligned muscle fibers. Moreover, after in vivo orthotopic implantation in a surgical CDH mouse model, mechanically stimulated muscles maintained the presence of human cells within myofibers and hernia recurrence did not occur, suggesting the value of this approach for treating diaphragm defects. Nature Publishing Group UK 2022-04-25 /pmc/articles/PMC9038738/ /pubmed/35468920 http://dx.doi.org/10.1038/s41536-022-00222-x Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Maghin, Edoardo
Carraro, Eugenia
Boso, Daniele
Dedja, Arben
Giagante, Mattia
Caccin, Paola
Barna, Raluca Ana-Maria
Bresolin, Silvia
Cani, Alice
Borile, Giulia
Sandrin, Deborah
Romanato, Filippo
Cecchinato, Francesca
Urciuolo, Anna
Sandonà, Dorianna
De Coppi, Paolo
Pavan, Piero G.
Piccoli, Martina
Customized bioreactor enables the production of 3D diaphragmatic constructs influencing matrix remodeling and fibroblast overgrowth
title Customized bioreactor enables the production of 3D diaphragmatic constructs influencing matrix remodeling and fibroblast overgrowth
title_full Customized bioreactor enables the production of 3D diaphragmatic constructs influencing matrix remodeling and fibroblast overgrowth
title_fullStr Customized bioreactor enables the production of 3D diaphragmatic constructs influencing matrix remodeling and fibroblast overgrowth
title_full_unstemmed Customized bioreactor enables the production of 3D diaphragmatic constructs influencing matrix remodeling and fibroblast overgrowth
title_short Customized bioreactor enables the production of 3D diaphragmatic constructs influencing matrix remodeling and fibroblast overgrowth
title_sort customized bioreactor enables the production of 3d diaphragmatic constructs influencing matrix remodeling and fibroblast overgrowth
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9038738/
https://www.ncbi.nlm.nih.gov/pubmed/35468920
http://dx.doi.org/10.1038/s41536-022-00222-x
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