Screening of perfused combinatorial 3D microenvironments for cell culture
Autor(a) principal: | |
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Data de Publicação: | 2019 |
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/1822/63448 |
Resumo: | Biomaterials combining biochemical and biophysical cues to establish close-to-extracellular matrix (ECM) models have been explored for cell expansion and differentiation purposes. Multivariate arrays are used as material-saving and rapid-to-analyze platforms, which enable selecting hit-spotted formulations targeting specific cellular responses. However, these systems often lack the ability to emulate dynamic mechanical aspects that occur in specific biological milieus and affect physiological phenomena including stem cells differentiation, tumor progression, or matrix modulation. We report a tailor-made strategy to address the combined effect of flow and biochemical composition of three-dimensional (3D) biomaterials on cellular response. We suggest a simple-to-implement device comprising (i) a perforated platform accommodating miniaturized 3D biomaterials and (ii) a bioreactor that enables the incorporation of the biomaterial-containing array into a disposable perfusion chamber. The system was upscaled to parallelizable setups, increasing the number of analyzed platforms per independent experiment. As a proof-of-concept, porous chitosan scaffolds with 1 mm diameter were functionalized with combinations of 5 ECM and cell-cell contact-mediating proteins, relevant for bone and dental regeneration, corresponding to 32 protein combinatorial formulations. Mesenchymal stem cells adhesion and production of an early osteogenic marker were assessed on-chip on static and under-flow dynamic perfusion conditions. Different hit-spotted biomaterial formulations were detected for the different flow regimes using direct image analysis. Cell-binding proteins still poorly explored as biomaterials components amelogenin and E-cadherin - were here shown as relevant cell response modulators. Their combination with ECM cell-binding proteins - fibronectin, vitronectin, and type 1 collagen - rendered specific biomaterial combinations with high cell adhesion and ALP production under flow. The developed versatile system may be targeted at w |
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Screening of perfused combinatorial 3D microenvironments for cell cultureFlow perfusionHigh-throughput screening3D microenvironmentsStem cell differentiationCell-matrix interactionsScience & TechnologyBiomaterials combining biochemical and biophysical cues to establish close-to-extracellular matrix (ECM) models have been explored for cell expansion and differentiation purposes. Multivariate arrays are used as material-saving and rapid-to-analyze platforms, which enable selecting hit-spotted formulations targeting specific cellular responses. However, these systems often lack the ability to emulate dynamic mechanical aspects that occur in specific biological milieus and affect physiological phenomena including stem cells differentiation, tumor progression, or matrix modulation. We report a tailor-made strategy to address the combined effect of flow and biochemical composition of three-dimensional (3D) biomaterials on cellular response. We suggest a simple-to-implement device comprising (i) a perforated platform accommodating miniaturized 3D biomaterials and (ii) a bioreactor that enables the incorporation of the biomaterial-containing array into a disposable perfusion chamber. The system was upscaled to parallelizable setups, increasing the number of analyzed platforms per independent experiment. As a proof-of-concept, porous chitosan scaffolds with 1 mm diameter were functionalized with combinations of 5 ECM and cell-cell contact-mediating proteins, relevant for bone and dental regeneration, corresponding to 32 protein combinatorial formulations. Mesenchymal stem cells adhesion and production of an early osteogenic marker were assessed on-chip on static and under-flow dynamic perfusion conditions. Different hit-spotted biomaterial formulations were detected for the different flow regimes using direct image analysis. Cell-binding proteins still poorly explored as biomaterials components amelogenin and E-cadherin - were here shown as relevant cell response modulators. Their combination with ECM cell-binding proteins - fibronectin, vitronectin, and type 1 collagen - rendered specific biomaterial combinations with high cell adhesion and ALP production under flow. The developed versatile system may be targeted at wM.B. Oliveira acknowledges the financial support from Portuguese Foundation for Science and Technology- FCT (Grant SFRH/BPD/111354/2015). This work was developed within the scope of the projects CICECO-Aveiro Institute of Materials, POCI-01-0145-FEDER-007679 (FCT Ref. UID/CTM/50011/2013) and IPC/i3N Minho (FCT Ref. UID/CTM/50025/2013), financed by national funds through the FCT/MEC and when appropriate co-financed by FEDER under the PT2020 Partnership Agreement. This work was also supported by European Research Council grant agreement ERC-2014-ADG-669858 (project ATLAS).ElsevierUniversidade do MinhoLopes, DianaFernandes, C.Miguel Nobrega, J.Patricio, Sonia G.Oliveira, Mariana BragaMano, J. F.2019-09-152019-09-15T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/1822/63448eng1742-706110.1016/j.actbio.2019.06.04731255663https://www.sciencedirect.com/science/article/pii/S1742706119304696?via%3Dihubinfo: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:RCAAP2023-07-21T12:43:41Zoai:repositorium.sdum.uminho.pt:1822/63448Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T19:41:13.494375Repositório 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 |
Screening of perfused combinatorial 3D microenvironments for cell culture |
title |
Screening of perfused combinatorial 3D microenvironments for cell culture |
spellingShingle |
Screening of perfused combinatorial 3D microenvironments for cell culture Lopes, Diana Flow perfusion High-throughput screening 3D microenvironments Stem cell differentiation Cell-matrix interactions Science & Technology |
title_short |
Screening of perfused combinatorial 3D microenvironments for cell culture |
title_full |
Screening of perfused combinatorial 3D microenvironments for cell culture |
title_fullStr |
Screening of perfused combinatorial 3D microenvironments for cell culture |
title_full_unstemmed |
Screening of perfused combinatorial 3D microenvironments for cell culture |
title_sort |
Screening of perfused combinatorial 3D microenvironments for cell culture |
author |
Lopes, Diana |
author_facet |
Lopes, Diana Fernandes, C. Miguel Nobrega, J. Patricio, Sonia G. Oliveira, Mariana Braga Mano, J. F. |
author_role |
author |
author2 |
Fernandes, C. Miguel Nobrega, J. Patricio, Sonia G. Oliveira, Mariana Braga Mano, J. F. |
author2_role |
author author author author author |
dc.contributor.none.fl_str_mv |
Universidade do Minho |
dc.contributor.author.fl_str_mv |
Lopes, Diana Fernandes, C. Miguel Nobrega, J. Patricio, Sonia G. Oliveira, Mariana Braga Mano, J. F. |
dc.subject.por.fl_str_mv |
Flow perfusion High-throughput screening 3D microenvironments Stem cell differentiation Cell-matrix interactions Science & Technology |
topic |
Flow perfusion High-throughput screening 3D microenvironments Stem cell differentiation Cell-matrix interactions Science & Technology |
description |
Biomaterials combining biochemical and biophysical cues to establish close-to-extracellular matrix (ECM) models have been explored for cell expansion and differentiation purposes. Multivariate arrays are used as material-saving and rapid-to-analyze platforms, which enable selecting hit-spotted formulations targeting specific cellular responses. However, these systems often lack the ability to emulate dynamic mechanical aspects that occur in specific biological milieus and affect physiological phenomena including stem cells differentiation, tumor progression, or matrix modulation. We report a tailor-made strategy to address the combined effect of flow and biochemical composition of three-dimensional (3D) biomaterials on cellular response. We suggest a simple-to-implement device comprising (i) a perforated platform accommodating miniaturized 3D biomaterials and (ii) a bioreactor that enables the incorporation of the biomaterial-containing array into a disposable perfusion chamber. The system was upscaled to parallelizable setups, increasing the number of analyzed platforms per independent experiment. As a proof-of-concept, porous chitosan scaffolds with 1 mm diameter were functionalized with combinations of 5 ECM and cell-cell contact-mediating proteins, relevant for bone and dental regeneration, corresponding to 32 protein combinatorial formulations. Mesenchymal stem cells adhesion and production of an early osteogenic marker were assessed on-chip on static and under-flow dynamic perfusion conditions. Different hit-spotted biomaterial formulations were detected for the different flow regimes using direct image analysis. Cell-binding proteins still poorly explored as biomaterials components amelogenin and E-cadherin - were here shown as relevant cell response modulators. Their combination with ECM cell-binding proteins - fibronectin, vitronectin, and type 1 collagen - rendered specific biomaterial combinations with high cell adhesion and ALP production under flow. The developed versatile system may be targeted at w |
publishDate |
2019 |
dc.date.none.fl_str_mv |
2019-09-15 2019-09-15T00:00:00Z |
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/1822/63448 |
url |
http://hdl.handle.net/1822/63448 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
1742-7061 10.1016/j.actbio.2019.06.047 31255663 https://www.sciencedirect.com/science/article/pii/S1742706119304696?via%3Dihub |
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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RCAAP |
institution |
RCAAP |
reponame_str |
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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