title: A planar model of the vessel wall from cellularized-collagen scaffolds: focus on cell-matrix interactions in mono-, bi- and tri-culture models.
abstract: The acquisition of new thorough knowledge on the interactions existing between vascular cells would represent a step forward in the engineering of vascular tissues. In this light, herein we designed a physiological-like tri-culture in vitro vascular wall model using a planar cellularized collagen gel as the scaffold. The model can be obtained in 24 h and features multi-layered hierarchical organization composed of a fibroblast-containing adventitia-like layer, a media-like layer populated by smooth muscle cells and an intima-like endothelial cell monolayer. After 7 days of static culture, the compaction of the collagen matrix by the vascular cells was achieved, and the deposition of the vascular extracellular matrix components fibronectin, fibrillin-1 and tropoelastin was observed. The blood-compatible functionality of the endothelial cell monolayer was demonstrated by a blood clotting assay: after 7 days of maturation, clotting was prevented on the endothelialized constructs (more than 80% free hemoglobin maintained after 60 min of blood contact) but not at all on non-endothelialized ones (less than 20% free hemoglobin). In addition, western blotting results suggested that in the tri-culture model the loss of smooth muscle cell phenotype was delayed compared to what was observed in the mono-culture model, finally resulting in a behaviour more similar to the in vivo conditions. Overall, our findings indicate that this in vitro model has the potential to be used as an advanced system to examine vascular cell behavioural interactions, as well as for drug testing and the investigation of physiological and pathological processes.
authors.affiliation: Laboratory for Biomaterials and Bioengineering, Canada Research Chair I in Biomaterials and Bioengineering for the Innovation in Surgery, Department of Min-Met-Materials Engineering, Research Center of CHU de Quebec, Division of Regenerative Medicine, Laval University, Quebec, QC, Canada G1V 0A6. diego.mantovani@gmn.ulaval.ca.
authors.forename: Caroline
authors.initials: C
authors.lastname: Loy
authors.affiliation: Laboratory for Biomaterials and Bioengineering, Canada Research Chair I in Biomaterials and Bioengineering for the Innovation in Surgery, Department of Min-Met-Materials Engineering, Research Center of CHU de Quebec, Division of Regenerative Medicine, Laval University, Quebec, QC, Canada G1V 0A6. diego.mantovani@gmn.ulaval.ca.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Meghezi
authors.affiliation: Laboratory for Biomaterials and Bioengineering, Canada Research Chair I in Biomaterials and Bioengineering for the Innovation in Surgery, Department of Min-Met-Materials Engineering, Research Center of CHU de Quebec, Division of Regenerative Medicine, Laval University, Quebec, QC, Canada G1V 0A6. diego.mantovani@gmn.ulaval.ca.
authors.forename: Lucie
authors.initials: L
authors.lastname: Lévesque
authors.affiliation: Laboratory for Biomaterials and Bioengineering, Canada Research Chair I in Biomaterials and Bioengineering for the Innovation in Surgery, Department of Min-Met-Materials Engineering, Research Center of CHU de Quebec, Division of Regenerative Medicine, Laval University, Quebec, QC, Canada G1V 0A6. diego.mantovani@gmn.ulaval.ca.
authors.forename: Daniele
authors.initials: D
authors.lastname: Pezzoli
authors.affiliation: Faculty of Medicine, Department of Anatomy and Cell Biology, and Faculty of Dentistry McGill University, Montréal, QC, Canada H3A 0C7.
authors.forename: Heena
authors.initials: H
authors.lastname: Kumra
authors.affiliation: Faculty of Medicine, Department of Anatomy and Cell Biology, and Faculty of Dentistry McGill University, Montréal, QC, Canada H3A 0C7.
authors.forename: Dieter
authors.initials: D
authors.lastname: Reinhardt
authors.affiliation: Centre for Blood Research, Department of Pathology and Laboratory Medicine, Department of Chemistry, University of British Columbia, Vancouver, BC, Canada V6T 1Z3.
authors.forename: Jayachandran N
authors.initials: JN
authors.lastname: Kizhakkedathu
authors.affiliation: Laboratory for Biomaterials and Bioengineering, Canada Research Chair I in Biomaterials and Bioengineering for the Innovation in Surgery, Department of Min-Met-Materials Engineering, Research Center of CHU de Quebec, Division of Regenerative Medicine, Laval University, Quebec, QC, Canada G1V 0A6. diego.mantovani@gmn.ulaval.ca.
authors.forename: Diego
authors.initials: D
authors.lastname: Mantovani
mesh_terms: D002478:Cells, Cultured; D003094:Collagen / Q000737:chemistry*; D005109:Extracellular Matrix / Q000378:metabolism*; D006801:Humans; D008954:Models, Biological; D032389:Myocytes, Smooth Muscle / Q000737:chemistry / Q000166:cytology / Q000378:metabolism*
chemical_list: D003094:Collagen