Novel bioprinted 3D model to human fibrosis investigation

Fibrosis is shared in multiple diseases with progressive tissue stiffening, organ failure and limited therapeutic options. This unmet need is also due to the lack of adequate pre-clinical models to mimic fibrosis and to be challenged novel by anti-fibrotic therapeutic venues. Here using bioprinting,...

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Main Authors: Tiziana Petrachi, Alberto Portone, Gaëlle Françoise Arnaud, Francesco Ganzerli, Valentina Bergamini, Elisa Resca, Luca Accorsi, Alberto Ferrari, Annalisa Delnevo, Luigi Rovati, Caterina Marra, Chiara Chiavelli, Massimo Dominici, Elena Veronesi
Format: Article
Language:English
Published: Elsevier 2023-09-01
Series:Biomedicine & Pharmacotherapy
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S075333222300937X
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author Tiziana Petrachi
Alberto Portone
Gaëlle Françoise Arnaud
Francesco Ganzerli
Valentina Bergamini
Elisa Resca
Luca Accorsi
Alberto Ferrari
Annalisa Delnevo
Luigi Rovati
Caterina Marra
Chiara Chiavelli
Massimo Dominici
Elena Veronesi
author_facet Tiziana Petrachi
Alberto Portone
Gaëlle Françoise Arnaud
Francesco Ganzerli
Valentina Bergamini
Elisa Resca
Luca Accorsi
Alberto Ferrari
Annalisa Delnevo
Luigi Rovati
Caterina Marra
Chiara Chiavelli
Massimo Dominici
Elena Veronesi
author_sort Tiziana Petrachi
collection DOAJ
description Fibrosis is shared in multiple diseases with progressive tissue stiffening, organ failure and limited therapeutic options. This unmet need is also due to the lack of adequate pre-clinical models to mimic fibrosis and to be challenged novel by anti-fibrotic therapeutic venues. Here using bioprinting, we designed a novel 3D model where normal human healthy fibroblasts have been encapsulated in type I collagen. After stimulation by Transforming Growth factor beta (TGFβ), embedded cells differentiated into myofibroblasts and enhanced the contractile activity, as confirmed by the high level of α − smooth muscle actin (αSMA) and F-actin expression. As functional assays, SEM analysis revealed that after TGFβ stimulus the 3D microarchitecture of the scaffold was dramatically remolded with an increased fibronectin deposition with an abnormal collagen fibrillar pattern. Picrius Sirius Red staining additionally revealed that TGFβ stimulation enhanced of two logarithm the collagen fibrils neoformation in comparison with control. These data indicate that by bioprinting technology, it is possible to generate a reproducible and functional 3D platform to mimic fibrosis as key tool for drug discovery and impacting on animal experimentation and reducing costs and time in addressing fibrosis.
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spelling doaj.art-831848e379964eceb921424d32e56e352023-08-13T04:52:45ZengElsevierBiomedicine & Pharmacotherapy0753-33222023-09-01165115146Novel bioprinted 3D model to human fibrosis investigationTiziana Petrachi0Alberto Portone1Gaëlle Françoise Arnaud2Francesco Ganzerli3Valentina Bergamini4Elisa Resca5Luca Accorsi6Alberto Ferrari7Annalisa Delnevo8Luigi Rovati9Caterina Marra10Chiara Chiavelli11Massimo Dominici12Elena Veronesi13Technopole “Mario Veronesi”, via 29 Maggio 6, 41037 Mirandola, ItalyTechnopole “Mario Veronesi”, via 29 Maggio 6, 41037 Mirandola, ItalyTechnopole “Mario Veronesi”, via 29 Maggio 6, 41037 Mirandola, Italy; Clinical and Experimental Medicine PhD program, University of Modena and Reggio Emilia, Italy; Department of Engineering ''Enzo Ferrari'', University of Modena and Reggio Emilia, via Vivarelli, 10, Building 26, 41124 Modena, Italy; Department of Medical and Surgical Sciences for Children & Adults, University of Modena and Reggio Emilia, Hospital of Modena, Via del Pozzo, 71, 44125 Modena, ItalyTechnopole “Mario Veronesi”, via 29 Maggio 6, 41037 Mirandola, ItalyTechnopole “Mario Veronesi”, via 29 Maggio 6, 41037 Mirandola, Italy; Clinical and Experimental Medicine PhD program, University of Modena and Reggio Emilia, ItalyTechnopole “Mario Veronesi”, via 29 Maggio 6, 41037 Mirandola, ItalyTechnopole “Mario Veronesi”, via 29 Maggio 6, 41037 Mirandola, ItalyTechnopole “Mario Veronesi”, via 29 Maggio 6, 41037 Mirandola, Italy; Department of Engineering ''Enzo Ferrari'', University of Modena and Reggio Emilia, via Vivarelli, 10, Building 26, 41124 Modena, ItalyTechnopole “Mario Veronesi”, via 29 Maggio 6, 41037 Mirandola, ItalyDepartment of Engineering ''Enzo Ferrari'', University of Modena and Reggio Emilia, via Vivarelli, 10, Building 26, 41124 Modena, ItalyDepartment of Medical and Surgical Sciences for Children & Adults, University of Modena and Reggio Emilia, Hospital of Modena, Via del Pozzo, 71, 44125 Modena, ItalyDepartment of Medical and Surgical Sciences for Children & Adults, University of Modena and Reggio Emilia, Hospital of Modena, Via del Pozzo, 71, 44125 Modena, ItalyDepartment of Medical and Surgical Sciences for Children & Adults, University of Modena and Reggio Emilia, Hospital of Modena, Via del Pozzo, 71, 44125 Modena, ItalyTechnopole “Mario Veronesi”, via 29 Maggio 6, 41037 Mirandola, Italy; Corresponding author.Fibrosis is shared in multiple diseases with progressive tissue stiffening, organ failure and limited therapeutic options. This unmet need is also due to the lack of adequate pre-clinical models to mimic fibrosis and to be challenged novel by anti-fibrotic therapeutic venues. Here using bioprinting, we designed a novel 3D model where normal human healthy fibroblasts have been encapsulated in type I collagen. After stimulation by Transforming Growth factor beta (TGFβ), embedded cells differentiated into myofibroblasts and enhanced the contractile activity, as confirmed by the high level of α − smooth muscle actin (αSMA) and F-actin expression. As functional assays, SEM analysis revealed that after TGFβ stimulus the 3D microarchitecture of the scaffold was dramatically remolded with an increased fibronectin deposition with an abnormal collagen fibrillar pattern. Picrius Sirius Red staining additionally revealed that TGFβ stimulation enhanced of two logarithm the collagen fibrils neoformation in comparison with control. These data indicate that by bioprinting technology, it is possible to generate a reproducible and functional 3D platform to mimic fibrosis as key tool for drug discovery and impacting on animal experimentation and reducing costs and time in addressing fibrosis.http://www.sciencedirect.com/science/article/pii/S075333222300937XFibrosisBioprintingDisease modeling, testing, extracellular matrix
spellingShingle Tiziana Petrachi
Alberto Portone
Gaëlle Françoise Arnaud
Francesco Ganzerli
Valentina Bergamini
Elisa Resca
Luca Accorsi
Alberto Ferrari
Annalisa Delnevo
Luigi Rovati
Caterina Marra
Chiara Chiavelli
Massimo Dominici
Elena Veronesi
Novel bioprinted 3D model to human fibrosis investigation
Biomedicine & Pharmacotherapy
Fibrosis
Bioprinting
Disease modeling, testing, extracellular matrix
title Novel bioprinted 3D model to human fibrosis investigation
title_full Novel bioprinted 3D model to human fibrosis investigation
title_fullStr Novel bioprinted 3D model to human fibrosis investigation
title_full_unstemmed Novel bioprinted 3D model to human fibrosis investigation
title_short Novel bioprinted 3D model to human fibrosis investigation
title_sort novel bioprinted 3d model to human fibrosis investigation
topic Fibrosis
Bioprinting
Disease modeling, testing, extracellular matrix
url http://www.sciencedirect.com/science/article/pii/S075333222300937X
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