Reference : UMR8640-CARAIM-001
Nombre de Postes : 1
Workplace : PARIS 05
Date of publication : Monday, January 23, 2023
Type of Contract : FTC Scientist
Contract Period : 18 months
Expected date of employment : 1 March 2023
Proportion of work : Full time
Remuneration : 2889 et 4581 euros bruts par mois
Desired level of education : PhD
Experience required : Indifferent
There is an extensive medical and societal need for the development of vascularized tissue models for regenerative medicine and replacement of animal models. Biomimetic models based on microfluidics are a promising avenue. This project aims at developing a vascularized tissue model with microfabricated 3D devices and collagen hydrogels co-seeded with endothelial cells and mesenchymal stem cells.
Since the first reports of skin model on a chip , skin equivalents have been interfaced with vascular endothelial models. Typically, endothelial cells were seeded to grow as monolayers either on porous membranes [2,3] or microfabricated channels  but not allowed to generate microvascular structures. Connecting fabricated channels to self-assembled endothelial microvessels is a major challenge. The ASTER project aims at creating such relevant and functional perfused microvascular models. To this aim, we microfabricate porous supports, which exhibit a controlled and patterned number of pores. On the bottom side of the support, a monolayer of endothelial cells is grown, while the top side hosts a collagen hydrogel loaded with stem cells. Preliminary results have shown that endothelial cells invade the hydrogel through the pores and form de novo vascular structures having an aster shape. This process called sprouting results in the formation of actual lumenized microvessels. The vascular, aster-like structures, can then fuse via anastomosis thus forming a luminized vascular network.
Such generation of microvascular network from an endothelial monolayer is a unique model, in a very active area of research. Tuning the dimensions and distribution of the pores in this unique setup will provide control of the hierarchical structure of vascular networks. As such, ASTER will provide a key platform to address fundamental questions in biology about the drivers of sprouting and anastomosis. In addition, the integration of this vascularized model in a microfluidic chip will open doors for setting up therapeutic assays.
 Abaci et al. LabChip 2015 15, 882;  Wufuer et al. SciRep 2016 6, 37471;  Kwak et al. BiotechnolBioeng 2020 117, 1853;  Lee et al. BiomedMicrodevices 2017 19, 22.
The postdoctoral fellow will have five main missions:
(1) Microfabrication of porous supports
(2) Optimization of co-culture conditions including endothelial cells, mesenchymal stem cells and fibroblasts
(3) 3D characterization of vascular networks (cross-section area, capillary length, branching)
(4) Perfusion of the vascularized networks
(5) Investigation of the impact of shear stress on the maturation of vascular networks
The postdoctoral fellow will work on the development of microfabricated platforms and microfluidic devices for exploring the formation and hierarchical organization of vascular structures – sprouting and anastomosis. She/he will then implement the perfusion of the resulting vascular network.
A good candidate would have skills in biomaterials engineering and cell biology. A strong interest or background in (bio)microfluidics will also be appreciated.
The research activity will be carried out on a full-time work week, within the PASTEUR (ENS) and CIRB (Collège de France) laboratories, 800 m apart. The postdoctoral fellow will have an office and lab space to work in both laboratories.
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