Integrin-specific hydrogels for growth factor-free vasculogenesis
Autor(a) principal: | |
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Data de Publicação: | 2022 |
Outros Autores: | , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | https://hdl.handle.net/1822/81629 |
Resumo: | Integrin-binding biomaterials have been extensively evaluated for their capacity to enable de novo formation of capillary-like structures/vessels, ultimately supporting neovascularization in vivo. Yet, the role of integrins as vascular initiators in engineered materials is still not well understood. Here, we show that αvβ3 integrin-specific 3D matrices were able to retain PECAM1+ cells from the stromal vascular fraction (SVF) of adipose tissue, triggering vasculogenesis in vitro in the absence of extrinsic growth factors. Our results suggest that αvβ3-RGD-driven signaling in the formation of capillary-like structures prevents the activation of the caspase 8 pathway and activates the FAK/paxillin pathway, both responsible for endothelial cells (ECs) survival and migration. We also show that prevascularized αvβ3 integrin-specific constructs inosculate with the host vascular system fostering in vivo neovascularization. Overall, this work demonstrates the ability of the biomaterial to trigger vasculogenesis in an integrin-specific manner, by activating essential pathways for EC survival and migration within a self-regulatory growth factor microenvironment. This strategy represents an improvement to current vascularization routes for Tissue Engineering constructs, potentially enhancing their clinical applicability. |
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Integrin-specific hydrogels for growth factor-free vasculogenesisBiomaterialsStromal vascular fractionVascularizationVasculogenesisScience & TechnologyIntegrin-binding biomaterials have been extensively evaluated for their capacity to enable de novo formation of capillary-like structures/vessels, ultimately supporting neovascularization in vivo. Yet, the role of integrins as vascular initiators in engineered materials is still not well understood. Here, we show that αvβ3 integrin-specific 3D matrices were able to retain PECAM1+ cells from the stromal vascular fraction (SVF) of adipose tissue, triggering vasculogenesis in vitro in the absence of extrinsic growth factors. Our results suggest that αvβ3-RGD-driven signaling in the formation of capillary-like structures prevents the activation of the caspase 8 pathway and activates the FAK/paxillin pathway, both responsible for endothelial cells (ECs) survival and migration. We also show that prevascularized αvβ3 integrin-specific constructs inosculate with the host vascular system fostering in vivo neovascularization. Overall, this work demonstrates the ability of the biomaterial to trigger vasculogenesis in an integrin-specific manner, by activating essential pathways for EC survival and migration within a self-regulatory growth factor microenvironment. This strategy represents an improvement to current vascularization routes for Tissue Engineering constructs, potentially enhancing their clinical applicability.The authors would like to acknowledge the financial support from the Consolidator Grant “ECM_INK” (ERC-2016-COG-726061) and the Starting Grant “CapBed” (ERC2018-STG-805411), to the FSE/POCH (Fundo Social Europeu através do Programa Operacional do Capital Humano) under the scope of the PD/169/2013, NORTE-08- 5369-FSE-000037 (H.R.M.), and to FCT/MCTES (Fundação para a Ciência e a Tecnologia/ Ministério da Ciência, Tecnologia, e Ensino Superior) through the grants SFRH/BD/119756/2016 (D.B.R.), Ph.D. grant PD/BD/135252/2017 (S.F.R.) and IF/00347/ 2015 (R.P.P.).Springer NatureUniversidade do MinhoMoreira, Helena R.Rodrigues, Daniel BarreiraRibeiro, Sara FreitasSilva, Lucília PereiraMorais, Alain da S.Jarnalo, MarianaHorta, RicardoReis, R. L.Pirraco, Rogério P.Marques, A. P.2022-092022-09-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/1822/81629engMoreira H. R., Rodrigues D. B., Freitas-Ribeiro S., da Silva L. P., Morais A., Jalano M., Horta R., Reis R. L., Pirraco R. P., Marques A. P. Integrin-specific hydrogels for growth factor-free vasculogenesis, npj Regenerative Medicine, Vol. 7, pp. 57, doi:10.1038/s41536-022-00253-4, 20222057-399510.1038/s41536-022-00253-457https://www.nature.com/articles/s41536-022-00253-4info: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:RCAAP2023-07-21T12:44:20Zoai:repositorium.sdum.uminho.pt:1822/81629Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T19:42:00.618019Repositório 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 |
Integrin-specific hydrogels for growth factor-free vasculogenesis |
title |
Integrin-specific hydrogels for growth factor-free vasculogenesis |
spellingShingle |
Integrin-specific hydrogels for growth factor-free vasculogenesis Moreira, Helena R. Biomaterials Stromal vascular fraction Vascularization Vasculogenesis Science & Technology |
title_short |
Integrin-specific hydrogels for growth factor-free vasculogenesis |
title_full |
Integrin-specific hydrogels for growth factor-free vasculogenesis |
title_fullStr |
Integrin-specific hydrogels for growth factor-free vasculogenesis |
title_full_unstemmed |
Integrin-specific hydrogels for growth factor-free vasculogenesis |
title_sort |
Integrin-specific hydrogels for growth factor-free vasculogenesis |
author |
Moreira, Helena R. |
author_facet |
Moreira, Helena R. Rodrigues, Daniel Barreira Ribeiro, Sara Freitas Silva, Lucília Pereira Morais, Alain da S. Jarnalo, Mariana Horta, Ricardo Reis, R. L. Pirraco, Rogério P. Marques, A. P. |
author_role |
author |
author2 |
Rodrigues, Daniel Barreira Ribeiro, Sara Freitas Silva, Lucília Pereira Morais, Alain da S. Jarnalo, Mariana Horta, Ricardo Reis, R. L. Pirraco, Rogério P. Marques, A. P. |
author2_role |
author author author author author author author author author |
dc.contributor.none.fl_str_mv |
Universidade do Minho |
dc.contributor.author.fl_str_mv |
Moreira, Helena R. Rodrigues, Daniel Barreira Ribeiro, Sara Freitas Silva, Lucília Pereira Morais, Alain da S. Jarnalo, Mariana Horta, Ricardo Reis, R. L. Pirraco, Rogério P. Marques, A. P. |
dc.subject.por.fl_str_mv |
Biomaterials Stromal vascular fraction Vascularization Vasculogenesis Science & Technology |
topic |
Biomaterials Stromal vascular fraction Vascularization Vasculogenesis Science & Technology |
description |
Integrin-binding biomaterials have been extensively evaluated for their capacity to enable de novo formation of capillary-like structures/vessels, ultimately supporting neovascularization in vivo. Yet, the role of integrins as vascular initiators in engineered materials is still not well understood. Here, we show that αvβ3 integrin-specific 3D matrices were able to retain PECAM1+ cells from the stromal vascular fraction (SVF) of adipose tissue, triggering vasculogenesis in vitro in the absence of extrinsic growth factors. Our results suggest that αvβ3-RGD-driven signaling in the formation of capillary-like structures prevents the activation of the caspase 8 pathway and activates the FAK/paxillin pathway, both responsible for endothelial cells (ECs) survival and migration. We also show that prevascularized αvβ3 integrin-specific constructs inosculate with the host vascular system fostering in vivo neovascularization. Overall, this work demonstrates the ability of the biomaterial to trigger vasculogenesis in an integrin-specific manner, by activating essential pathways for EC survival and migration within a self-regulatory growth factor microenvironment. This strategy represents an improvement to current vascularization routes for Tissue Engineering constructs, potentially enhancing their clinical applicability. |
publishDate |
2022 |
dc.date.none.fl_str_mv |
2022-09 2022-09-01T00:00:00Z |
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 |
https://hdl.handle.net/1822/81629 |
url |
https://hdl.handle.net/1822/81629 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Moreira H. R., Rodrigues D. B., Freitas-Ribeiro S., da Silva L. P., Morais A., Jalano M., Horta R., Reis R. L., Pirraco R. P., Marques A. P. Integrin-specific hydrogels for growth factor-free vasculogenesis, npj Regenerative Medicine, Vol. 7, pp. 57, doi:10.1038/s41536-022-00253-4, 2022 2057-3995 10.1038/s41536-022-00253-4 57 https://www.nature.com/articles/s41536-022-00253-4 |
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 |
Springer Nature |
publisher.none.fl_str_mv |
Springer Nature |
dc.source.none.fl_str_mv |
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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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1799132971555356672 |