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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Detalles Bibliográficos
Autores: López Canosa, Adrián, Pérez Amodio, Soledad Graciela|||0000-0001-6825-0194, Engel López, Elisabeth|||0000-0003-4855-8874, Castaño Linares, Óscar|||0000-0001-9212-784X
Tipo de recurso: artículo
Fecha de publicación:2022
País:España
Institución:Universitat Politècnica de Catalunya (UPC)
Repositorio:UPCommons. Portal del coneixement obert de la UPC
Idioma:inglés
OAI Identifier:oai:upcommons.upc.edu:2117/382758
Acceso en línea:https://hdl.handle.net/2117/382758
https://dx.doi.org/10.1016/j.actbio.2022.08.019
Access Level:acceso abierto
Palabra clave:Bone regeneration
Tissue engineering
Vascularization
Microfluidic model
Ion release
Bioactive materials
Signalling gradient
Ossos
Enginyeria de teixits
Àrees temàtiques de la UPC::Enginyeria biomèdica::Biomaterials
Descripción
Sumario: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.