Cell sheet technology-driven re-epithelialization and neovascularization of skin wounds
Autor(a) principal: | |
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Data de Publicação: | 2014 |
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/1822/35386 |
Resumo: | Skin regeneration remains a challenge, requiring a well-orchestrated interplay of cell–cell and cell–matrix signalling. Cell sheet (CS) engineering, which has the major advantage of allowing the retrieval of the intact cell layers along with their naturally organized extracellular matrix (ECM), has been poorly explored for the purpose of creating skin substitutes and skin regeneration. This work proposes the use of CS technology to engineer cellular constructs based on human keratinocytes (hKC), key players in wound re-epithelialization, dermal fibroblasts (hDFb), responsible for ECM remodelling, and dermal microvascular endothelial cells (hDMEC), part of the dermal vascular network and modulators of angiogenesis. Homotypic and heterotypic three-dimensional (3-D) CS-based constructs were developed simultaneously to target wound re-vascularization and re-epithelialization. After implantation of the constructs in murine full-thickness wounds, human cells were engrafted into the host wound bed and were present in the neotissue formed up to 14 days post-implantation. Different outcomes were obtained by varying the composition and organization of the 3-D constructs. Both hKC and hDMEC significantly contributed to re-epithelialization by promoting rapid wound closure and early epithelial coverage. Moreover, a significant increase in the density of vessels at day 7 and the incorporation of hDMEC in the neoformed vasculature confirmed its role over neotissue vacularization. As a whole, the obtained results confirmed that the proposed 3-D CS-based constructs provided the necessary cell machinery, when in a specific microenvironment, guiding both re-vascularization and re-epithelialization. Although dependent on the nature of the constructs, the results obtained sustain the hypothesis that different CS-based constructs lead to improved skin healing. |
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Cell sheet technology-driven re-epithelialization and neovascularization of skin woundsCell Sheet EngineeringSkin lineagesSkin regenerationWound healingScience & TechnologySkin regeneration remains a challenge, requiring a well-orchestrated interplay of cell–cell and cell–matrix signalling. Cell sheet (CS) engineering, which has the major advantage of allowing the retrieval of the intact cell layers along with their naturally organized extracellular matrix (ECM), has been poorly explored for the purpose of creating skin substitutes and skin regeneration. This work proposes the use of CS technology to engineer cellular constructs based on human keratinocytes (hKC), key players in wound re-epithelialization, dermal fibroblasts (hDFb), responsible for ECM remodelling, and dermal microvascular endothelial cells (hDMEC), part of the dermal vascular network and modulators of angiogenesis. Homotypic and heterotypic three-dimensional (3-D) CS-based constructs were developed simultaneously to target wound re-vascularization and re-epithelialization. After implantation of the constructs in murine full-thickness wounds, human cells were engrafted into the host wound bed and were present in the neotissue formed up to 14 days post-implantation. Different outcomes were obtained by varying the composition and organization of the 3-D constructs. Both hKC and hDMEC significantly contributed to re-epithelialization by promoting rapid wound closure and early epithelial coverage. Moreover, a significant increase in the density of vessels at day 7 and the incorporation of hDMEC in the neoformed vasculature confirmed its role over neotissue vacularization. As a whole, the obtained results confirmed that the proposed 3-D CS-based constructs provided the necessary cell machinery, when in a specific microenvironment, guiding both re-vascularization and re-epithelialization. Although dependent on the nature of the constructs, the results obtained sustain the hypothesis that different CS-based constructs lead to improved skin healing.The authors thank Hospital da Prelada (Porto), in particular Dr. Paulo Costa for lipoaspirate collection, and Skingineering (PTDC/SAU-OSM/099422/2008) for to financial support; a Portuguese Foundation for Science and Technology (FCT) funded project. The research leading to these results has also received funding from the European Union's Seventh Framework Programme (FP7/2007-2013) under grant agreement REGPOT-CT2012-316331-POLARIS.ElsevierUniversidade do MinhoCerqueira, M. T.Pirraco, Rogério P.Martins, A. R.Santos, T. C.Reis, R. L.Marques, A. P.2014-072014-07-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/1822/35386engCerqueira M. T., Pirraco R. P., Martins A. R., Santos T. C., Reis R. L., Marques A. P. Cell Sheet Technology-Driven Re-epithelialization and Neovascularization of Skin Wounds, Acta Biomaterialia, pp. pp 3145–3155, doi: 10.1016/j.actbio.2014.03.006. 20141742-706110.1016/j.actbio.2014.03.00624650971http://www.sciencedirect.com/science/article/pii/S1742706114001172#info: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:RCAAP2023-07-21T12:39:26Zoai:repositorium.sdum.uminho.pt:1822/35386Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T19:36:03.288740Repositório 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 |
Cell sheet technology-driven re-epithelialization and neovascularization of skin wounds |
title |
Cell sheet technology-driven re-epithelialization and neovascularization of skin wounds |
spellingShingle |
Cell sheet technology-driven re-epithelialization and neovascularization of skin wounds Cerqueira, M. T. Cell Sheet Engineering Skin lineages Skin regeneration Wound healing Science & Technology |
title_short |
Cell sheet technology-driven re-epithelialization and neovascularization of skin wounds |
title_full |
Cell sheet technology-driven re-epithelialization and neovascularization of skin wounds |
title_fullStr |
Cell sheet technology-driven re-epithelialization and neovascularization of skin wounds |
title_full_unstemmed |
Cell sheet technology-driven re-epithelialization and neovascularization of skin wounds |
title_sort |
Cell sheet technology-driven re-epithelialization and neovascularization of skin wounds |
author |
Cerqueira, M. T. |
author_facet |
Cerqueira, M. T. Pirraco, Rogério P. Martins, A. R. Santos, T. C. Reis, R. L. Marques, A. P. |
author_role |
author |
author2 |
Pirraco, Rogério P. Martins, A. R. Santos, T. C. Reis, R. L. Marques, A. P. |
author2_role |
author author author author author |
dc.contributor.none.fl_str_mv |
Universidade do Minho |
dc.contributor.author.fl_str_mv |
Cerqueira, M. T. Pirraco, Rogério P. Martins, A. R. Santos, T. C. Reis, R. L. Marques, A. P. |
dc.subject.por.fl_str_mv |
Cell Sheet Engineering Skin lineages Skin regeneration Wound healing Science & Technology |
topic |
Cell Sheet Engineering Skin lineages Skin regeneration Wound healing Science & Technology |
description |
Skin regeneration remains a challenge, requiring a well-orchestrated interplay of cell–cell and cell–matrix signalling. Cell sheet (CS) engineering, which has the major advantage of allowing the retrieval of the intact cell layers along with their naturally organized extracellular matrix (ECM), has been poorly explored for the purpose of creating skin substitutes and skin regeneration. This work proposes the use of CS technology to engineer cellular constructs based on human keratinocytes (hKC), key players in wound re-epithelialization, dermal fibroblasts (hDFb), responsible for ECM remodelling, and dermal microvascular endothelial cells (hDMEC), part of the dermal vascular network and modulators of angiogenesis. Homotypic and heterotypic three-dimensional (3-D) CS-based constructs were developed simultaneously to target wound re-vascularization and re-epithelialization. After implantation of the constructs in murine full-thickness wounds, human cells were engrafted into the host wound bed and were present in the neotissue formed up to 14 days post-implantation. Different outcomes were obtained by varying the composition and organization of the 3-D constructs. Both hKC and hDMEC significantly contributed to re-epithelialization by promoting rapid wound closure and early epithelial coverage. Moreover, a significant increase in the density of vessels at day 7 and the incorporation of hDMEC in the neoformed vasculature confirmed its role over neotissue vacularization. As a whole, the obtained results confirmed that the proposed 3-D CS-based constructs provided the necessary cell machinery, when in a specific microenvironment, guiding both re-vascularization and re-epithelialization. Although dependent on the nature of the constructs, the results obtained sustain the hypothesis that different CS-based constructs lead to improved skin healing. |
publishDate |
2014 |
dc.date.none.fl_str_mv |
2014-07 2014-07-01T00:00:00Z |
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 |
http://hdl.handle.net/1822/35386 |
url |
http://hdl.handle.net/1822/35386 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Cerqueira M. T., Pirraco R. P., Martins A. R., Santos T. C., Reis R. L., Marques A. P. Cell Sheet Technology-Driven Re-epithelialization and Neovascularization of Skin Wounds, Acta Biomaterialia, pp. pp 3145–3155, doi: 10.1016/j.actbio.2014.03.006. 2014 1742-7061 10.1016/j.actbio.2014.03.006 24650971 http://www.sciencedirect.com/science/article/pii/S1742706114001172# |
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 |
Elsevier |
publisher.none.fl_str_mv |
Elsevier |
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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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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