3D-printed gelatin methacrylate scaffolds with controlled architecture and stiffness modulate the fibroblast phenotype towards dermal regeneration
Autor(a) principal: | |
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Data de Publicação: | 2021 |
Outros Autores: | , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/1822/74354 |
Resumo: | Impaired skin wound healing due to severe injury often leads to dysfunctional scar tissue formation as a result of excessive and persistent myofibroblast activation, characterised by the increased expression of α-smooth muscle actin (αSMA) and extracellular matrix (ECM) proteins. Yet, despite extensive research on impaired wound healing and the advancement in tissue-engineered skin substitutes, scar formation remains a significant clinical challenge. This study aimed to first investigate the effect of methacrylate gelatin (GelMA) biomaterial stiffness on human dermal fibroblast behaviour in order to then design a range of 3D-printed GelMA scaffolds with tuneable structural and mechanical properties and understand whether the introduction of pores and porosity would support fibroblast activity, while inhibiting myofibroblast-related gene and protein expression. Results demonstrated that increasing GelMA stiffness promotes myofibroblast activation through increased fibrosis-related gene and protein expression. However, the introduction of a porous architecture by 3D printing facilitated healthy fibroblast activity, while inhibiting myofibroblast activation. A significant reduction was observed in the gene and protein production of αSMA and the expression of ECM-related proteins, including fibronectin I and collagen III, across the range of porous 3D-printed GelMA scaffolds. These results show that the 3D-printed GelMA scaffolds have the potential to improve dermal skin healing, whilst inhibiting fibrosis and scar formation, therefore potentially offering a new treatment for skin repair. |
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3D-printed gelatin methacrylate scaffolds with controlled architecture and stiffness modulate the fibroblast phenotype towards dermal regenerationBiomaterial stiffnessPorosityWound healingGelMA3D printingFibroblastFibrosis inhibitionScience & TechnologyImpaired skin wound healing due to severe injury often leads to dysfunctional scar tissue formation as a result of excessive and persistent myofibroblast activation, characterised by the increased expression of α-smooth muscle actin (αSMA) and extracellular matrix (ECM) proteins. Yet, despite extensive research on impaired wound healing and the advancement in tissue-engineered skin substitutes, scar formation remains a significant clinical challenge. This study aimed to first investigate the effect of methacrylate gelatin (GelMA) biomaterial stiffness on human dermal fibroblast behaviour in order to then design a range of 3D-printed GelMA scaffolds with tuneable structural and mechanical properties and understand whether the introduction of pores and porosity would support fibroblast activity, while inhibiting myofibroblast-related gene and protein expression. Results demonstrated that increasing GelMA stiffness promotes myofibroblast activation through increased fibrosis-related gene and protein expression. However, the introduction of a porous architecture by 3D printing facilitated healthy fibroblast activity, while inhibiting myofibroblast activation. A significant reduction was observed in the gene and protein production of αSMA and the expression of ECM-related proteins, including fibronectin I and collagen III, across the range of porous 3D-printed GelMA scaffolds. These results show that the 3D-printed GelMA scaffolds have the potential to improve dermal skin healing, whilst inhibiting fibrosis and scar formation, therefore potentially offering a new treatment for skin repair.The authors acknowledge funding from Science Foundation Ireland under the M-ERA.NET program, Transnational Call 2016 (17/US/3437; Ireland), EU BlueHuman Interreg Atlantic Area Project (grant EAPA_151/2016) and Science Foundation Ireland, through the Advanced Materials and BioEngineering Research Centre (AMBER; grants 12/RC/2278 and 12/RC/2278_P2).Multidisciplinary Digital Publishing Institute (MDPI)Universidade do MinhoR. Ibañez, Rita I.do Amaral, Ronaldo J. F. C.Reis, R. L.Marques, A. P.Murphy, Ciara M.O’Brien, Fergal J.2021-07-302021-07-30T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/1822/74354engR. Ibañez, R.I.; do Amaral, R.J.F.C.; Reis, R.L.; Marques, A.P.; Murphy, C.M.; O’Brien, F.J. 3D-Printed Gelatin Methacrylate Scaffolds with Controlled Architecture and Stiffness Modulate the Fibroblast Phenotype towards Dermal Regeneration. Polymers 2021, 13, 2510. https://doi.org/10.3390/polym131525102073-436010.3390/polym13152510https://www.mdpi.com/2073-4360/13/15/2510info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-07-21T11:55:00Zoai:repositorium.sdum.uminho.pt:1822/74354Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T18:44:28.861190Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
3D-printed gelatin methacrylate scaffolds with controlled architecture and stiffness modulate the fibroblast phenotype towards dermal regeneration |
title |
3D-printed gelatin methacrylate scaffolds with controlled architecture and stiffness modulate the fibroblast phenotype towards dermal regeneration |
spellingShingle |
3D-printed gelatin methacrylate scaffolds with controlled architecture and stiffness modulate the fibroblast phenotype towards dermal regeneration R. Ibañez, Rita I. Biomaterial stiffness Porosity Wound healing GelMA 3D printing Fibroblast Fibrosis inhibition Science & Technology |
title_short |
3D-printed gelatin methacrylate scaffolds with controlled architecture and stiffness modulate the fibroblast phenotype towards dermal regeneration |
title_full |
3D-printed gelatin methacrylate scaffolds with controlled architecture and stiffness modulate the fibroblast phenotype towards dermal regeneration |
title_fullStr |
3D-printed gelatin methacrylate scaffolds with controlled architecture and stiffness modulate the fibroblast phenotype towards dermal regeneration |
title_full_unstemmed |
3D-printed gelatin methacrylate scaffolds with controlled architecture and stiffness modulate the fibroblast phenotype towards dermal regeneration |
title_sort |
3D-printed gelatin methacrylate scaffolds with controlled architecture and stiffness modulate the fibroblast phenotype towards dermal regeneration |
author |
R. Ibañez, Rita I. |
author_facet |
R. Ibañez, Rita I. do Amaral, Ronaldo J. F. C. Reis, R. L. Marques, A. P. Murphy, Ciara M. O’Brien, Fergal J. |
author_role |
author |
author2 |
do Amaral, Ronaldo J. F. C. Reis, R. L. Marques, A. P. Murphy, Ciara M. O’Brien, Fergal J. |
author2_role |
author author author author author |
dc.contributor.none.fl_str_mv |
Universidade do Minho |
dc.contributor.author.fl_str_mv |
R. Ibañez, Rita I. do Amaral, Ronaldo J. F. C. Reis, R. L. Marques, A. P. Murphy, Ciara M. O’Brien, Fergal J. |
dc.subject.por.fl_str_mv |
Biomaterial stiffness Porosity Wound healing GelMA 3D printing Fibroblast Fibrosis inhibition Science & Technology |
topic |
Biomaterial stiffness Porosity Wound healing GelMA 3D printing Fibroblast Fibrosis inhibition Science & Technology |
description |
Impaired skin wound healing due to severe injury often leads to dysfunctional scar tissue formation as a result of excessive and persistent myofibroblast activation, characterised by the increased expression of α-smooth muscle actin (αSMA) and extracellular matrix (ECM) proteins. Yet, despite extensive research on impaired wound healing and the advancement in tissue-engineered skin substitutes, scar formation remains a significant clinical challenge. This study aimed to first investigate the effect of methacrylate gelatin (GelMA) biomaterial stiffness on human dermal fibroblast behaviour in order to then design a range of 3D-printed GelMA scaffolds with tuneable structural and mechanical properties and understand whether the introduction of pores and porosity would support fibroblast activity, while inhibiting myofibroblast-related gene and protein expression. Results demonstrated that increasing GelMA stiffness promotes myofibroblast activation through increased fibrosis-related gene and protein expression. However, the introduction of a porous architecture by 3D printing facilitated healthy fibroblast activity, while inhibiting myofibroblast activation. A significant reduction was observed in the gene and protein production of αSMA and the expression of ECM-related proteins, including fibronectin I and collagen III, across the range of porous 3D-printed GelMA scaffolds. These results show that the 3D-printed GelMA scaffolds have the potential to improve dermal skin healing, whilst inhibiting fibrosis and scar formation, therefore potentially offering a new treatment for skin repair. |
publishDate |
2021 |
dc.date.none.fl_str_mv |
2021-07-30 2021-07-30T00:00:00Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/1822/74354 |
url |
http://hdl.handle.net/1822/74354 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
R. Ibañez, R.I.; do Amaral, R.J.F.C.; Reis, R.L.; Marques, A.P.; Murphy, C.M.; O’Brien, F.J. 3D-Printed Gelatin Methacrylate Scaffolds with Controlled Architecture and Stiffness Modulate the Fibroblast Phenotype towards Dermal Regeneration. Polymers 2021, 13, 2510. https://doi.org/10.3390/polym13152510 2073-4360 10.3390/polym13152510 https://www.mdpi.com/2073-4360/13/15/2510 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
Multidisciplinary Digital Publishing Institute (MDPI) |
publisher.none.fl_str_mv |
Multidisciplinary Digital Publishing Institute (MDPI) |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
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RCAAP |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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