Microfluidic 3D platform to evaluate endothelial progenitor cell recruitment by bioactive materials

Most of the conventional in vitro models to test biomaterial-driven vascularization are too simplistic to recapitulate the complex interactions taking place in the actual cell microenvironment, which results in a poor prediction of the in vivo performance of the material. However, during the last de...

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Autores: Lopez-Canosa, Adrián, Perez-Amodio, Soledad, Engel, Elisabeth, Castaño Linares, Óscar
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2022
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/219546
Acceso en línea:https://hdl.handle.net/2445/219546
Access Level:acceso abierto
Palabra clave:Microfluídica
Cèl·lules
Calci
Teixit ossi
Microfluidics
Cells
Calcium
Bone
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spelling Microfluidic 3D platform to evaluate endothelial progenitor cell recruitment by bioactive materialsLopez-Canosa, AdriánPerez-Amodio, SoledadEngel, ElisabethCastaño Linares, ÓscarMicrofluídicaCèl·lulesCalciTeixit ossiMicrofluidicsCellsCalciumBoneMost of the conventional in vitro models to test biomaterial-driven vascularization are too simplistic to recapitulate the complex interactions taking place in the actual cell microenvironment, which results in a poor prediction of the in vivo performance of the material. However, during the last decade, cell culture models based on microfluidic technology have allowed attaining unprecedented levels of tissue biomimicry. In this work, we propose a microfluidic-based 3D model to evaluate the effect of bioactive biomaterials capable of releasing signaling cues (such as ions or proteins) in the recruitment of endogenous endothelial progenitor cells, a key step in the vascularization process. The usability of the platform is demonstrated using experimentally-validated finite element models and migration and proliferation studies with rat endothelial progenitor cells (rEPCs) and bone marrow-derived rat mesenchymal stromal cells (BM-rMSCs). As a proof of concept of biomaterial evaluation, the response of rEPCs to an electrospun composite made of polylactic acid with calcium phosphates nanoparticles (PLA+CaP) was compared in a co-culture microenvironment with BM-rMSC to a regular PLA control. Our results show a significantly higher rEPCs migration and the upregulation of several pro-inflammatory and proangiogenic proteins in the case of the PLA+CaP. The effects of osteopontin (OPN) on the rEPCs migratory response were also studied using this platform, suggesting its important role in mediating their recruitment to a calcium-rich microenvironment. This new tool could be applied to screen the capacity of a variety of bioactive scaffolds to induce vascularization and accelerate the preclinical testing of biomaterials. STATEMENT OF SIGNIFICANCE: For many years researchers have used neovascularization models to evaluate bioactive biomaterials both in vitro, with low predictive results due to their poor biomimicry and minimal control over cell cues such as spatiotemporal biomolecule signaling, and in vivo models, presenting drawbacks such as being highly costly, time-consuming, poor human extrapolation, and ethically controversial. We describe a compact microphysiological platform designed for the evaluation of proangiogenesis in biomaterials through the quantification of the level of sprouting in a mimicked endothelium able to react to gradients of biomaterial-released signals in a fibrin-based extracellular matrix. This model is a useful tool to perform preclinical trustworthy studies in tissue regeneration and to better understand the different elements involved in the complex process of vascularization.Elsevier B.V.2025202520222025info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion14 p.application/pdfapplication/pdfhttps://hdl.handle.net/2445/219546Articles publicats en revistes (Enginyeria Electrònica i Biomèdica)reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésReproducció del document publicat a: https://doi.org/10.1016/j.actbio.2022.08.019Acta Biomaterialia, 2022, vol. 151, p. 264-277https://doi.org/10.1016/j.actbio.2022.08.019cc-by-nc-nd (c) Lopez-Canosa, Adrián et al., 2022http://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:recercat.cat:2445/2195462026-05-29T05:05:01Z
dc.title.none.fl_str_mv Microfluidic 3D platform to evaluate endothelial progenitor cell recruitment by bioactive materials
title Microfluidic 3D platform to evaluate endothelial progenitor cell recruitment by bioactive materials
spellingShingle Microfluidic 3D platform to evaluate endothelial progenitor cell recruitment by bioactive materials
Lopez-Canosa, Adrián
Microfluídica
Cèl·lules
Calci
Teixit ossi
Microfluidics
Cells
Calcium
Bone
title_short Microfluidic 3D platform to evaluate endothelial progenitor cell recruitment by bioactive materials
title_full Microfluidic 3D platform to evaluate endothelial progenitor cell recruitment by bioactive materials
title_fullStr Microfluidic 3D platform to evaluate endothelial progenitor cell recruitment by bioactive materials
title_full_unstemmed Microfluidic 3D platform to evaluate endothelial progenitor cell recruitment by bioactive materials
title_sort Microfluidic 3D platform to evaluate endothelial progenitor cell recruitment by bioactive materials
dc.creator.none.fl_str_mv Lopez-Canosa, Adrián
Perez-Amodio, Soledad
Engel, Elisabeth
Castaño Linares, Óscar
author Lopez-Canosa, Adrián
author_facet Lopez-Canosa, Adrián
Perez-Amodio, Soledad
Engel, Elisabeth
Castaño Linares, Óscar
author_role author
author2 Perez-Amodio, Soledad
Engel, Elisabeth
Castaño Linares, Óscar
author2_role author
author
author
dc.subject.none.fl_str_mv Microfluídica
Cèl·lules
Calci
Teixit ossi
Microfluidics
Cells
Calcium
Bone
topic Microfluídica
Cèl·lules
Calci
Teixit ossi
Microfluidics
Cells
Calcium
Bone
description Most of the conventional in vitro models to test biomaterial-driven vascularization are too simplistic to recapitulate the complex interactions taking place in the actual cell microenvironment, which results in a poor prediction of the in vivo performance of the material. However, during the last decade, cell culture models based on microfluidic technology have allowed attaining unprecedented levels of tissue biomimicry. In this work, we propose a microfluidic-based 3D model to evaluate the effect of bioactive biomaterials capable of releasing signaling cues (such as ions or proteins) in the recruitment of endogenous endothelial progenitor cells, a key step in the vascularization process. The usability of the platform is demonstrated using experimentally-validated finite element models and migration and proliferation studies with rat endothelial progenitor cells (rEPCs) and bone marrow-derived rat mesenchymal stromal cells (BM-rMSCs). As a proof of concept of biomaterial evaluation, the response of rEPCs to an electrospun composite made of polylactic acid with calcium phosphates nanoparticles (PLA+CaP) was compared in a co-culture microenvironment with BM-rMSC to a regular PLA control. Our results show a significantly higher rEPCs migration and the upregulation of several pro-inflammatory and proangiogenic proteins in the case of the PLA+CaP. The effects of osteopontin (OPN) on the rEPCs migratory response were also studied using this platform, suggesting its important role in mediating their recruitment to a calcium-rich microenvironment. This new tool could be applied to screen the capacity of a variety of bioactive scaffolds to induce vascularization and accelerate the preclinical testing of biomaterials. STATEMENT OF SIGNIFICANCE: For many years researchers have used neovascularization models to evaluate bioactive biomaterials both in vitro, with low predictive results due to their poor biomimicry and minimal control over cell cues such as spatiotemporal biomolecule signaling, and in vivo models, presenting drawbacks such as being highly costly, time-consuming, poor human extrapolation, and ethically controversial. We describe a compact microphysiological platform designed for the evaluation of proangiogenesis in biomaterials through the quantification of the level of sprouting in a mimicked endothelium able to react to gradients of biomaterial-released signals in a fibrin-based extracellular matrix. This model is a useful tool to perform preclinical trustworthy studies in tissue regeneration and to better understand the different elements involved in the complex process of vascularization.
publishDate 2022
dc.date.none.fl_str_mv 2022
2025
2025
2025
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/219546
url https://hdl.handle.net/2445/219546
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.1016/j.actbio.2022.08.019
Acta Biomaterialia, 2022, vol. 151, p. 264-277
https://doi.org/10.1016/j.actbio.2022.08.019
dc.rights.none.fl_str_mv cc-by-nc-nd (c) Lopez-Canosa, Adrián et al., 2022
http://creativecommons.org/licenses/by-nc-nd/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc-by-nc-nd (c) Lopez-Canosa, Adrián et al., 2022
http://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 14 p.
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Elsevier B.V.
publisher.none.fl_str_mv Elsevier B.V.
dc.source.none.fl_str_mv Articles publicats en revistes (Enginyeria Electrònica i Biomèdica)
reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,811543

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