Description du sujet de thèse

We are searching profiles with skills and knowledge first in mechanical engineering, numerical simulation and additive manufacturing are highly compatible. Supplementary training in micro-nano-fabrication is an additional advantage but is not necessary.

-----------------------------------------------------------------------------------------------------
PhD project:

In the search for better conditions to culture in-vitro cells and tissues, the development of more pertinent biomaterials is an important research direction. In order to mimic the native extracellular matrices (ECM), which is a hydrogel-like material made mostly of collagen fibres, we need biomaterials which reproduce the biochemistry of these fibrillar ECMs, but also their micro-architecture (porosity, fibre dimensions and organization) and their mechanical properties (visco-elasticity). Usually, biomaterials are hydrogels in which the mechanical properties depend on the precursor concentration and the pore size of the material. Therefore, micro-architecture and mechanics are correlated and could not be independently tuned. In the LAAS-CNRS in Toulouse, we are developing new fibrillar scaffolds similar to the ECM using high resolution 3D-printing, allowing such decoupling, and we wish to characterize and predict their mechanical properties. In particular, our scaffolds are made of acrylate resin, shaped into sub-micrometric fibres having similar stiffness as collagen fibers, using two photon polymerization.

In collaboration with a team of researcher from the Clement Ader Institute in Toulouse (Florian Bugarin (Finite Element models), Vincent Velay (Behaviour law of materials) and Stéphane Segonds (Additive manufacturing)), the proposed PhD will work on 3 main axes:
- Scaffold fabrication in clean-room and their mechanical characterization.
- Development of numerical twins of these scaffolds using AI-enhanced finite element models, allowing the prediction of the mechanical properties of new scaffold designs.
- Automatised design of fibrillar biomaterials having the intended properties (porosity, fibre density, visco-elasticity…).

The first axis of this PhD proposal would be to continue the work of a previous doctoral researcher (Ianis Drobecq) for the fabrication of these scaffolds (see pictures above). In order to obtain low stiffnesses while keeping a large density of fibres, the candidate will develop scaffolds with less links between fibres. Maps of mechanical properties will be realized by analysis of images obtained from micro-compression tests (home-made apparatus and atomic force microscopy).
On the second axis, the and their stiffness (obtained by AFM). An approach called Finite candidate will develop a Finite Element model of these fibrillar scaffolds, having as inputs the fibre diameters and organization Element Method Updated will be set up to fine tune the model parameters by comparing it with the experimental displacement field. This way, the candidate will develop numerical twins, allowing the prediction of the mechanical properties of new design before their printing.
In the third axis, the numerical problem will be inverted in order to obtain the best scaffold designs for a set of input parameters. Here, the candidate will set up an algorithm for topological optimization, producing fibrillar organization allowing to obtain the searched mean porosity and mechanical properties, by starting from a dense fibre network and by removing iteratively fibres or links. The results will be compared with printed scaffolds.
During all the PhD, biological validations of the pertinence of the printed scaffolds will be possible, thanks to a close collaboration with Alexis Arcas, working for his PhD thesis on the use of scaffolds for the culture of intestinal fibroblasts.

Tasks and techniques:

3D printing:
The future candidate will learn how to print these scaffolds using two photon polymerization (Nanoscribe PPGT+ printer) in the clean room environment of the LAAS-CNRS. Characterization will include electronic microscopy and fluorescent confocal microscopy.

Mechanical characterization:
The mechanical properties will be obtained using several techniques. We developed first a home-made micro-compression technique, coupled with fluorescent microscopy. Single fibre could be characterized using AFM. Finally, more exploratory techniques will be tested, including optical tweezers.

Numerical models:
From the inputs of the previous techniques, the candidate will have to develop several algorithms, including Finite Element Model using Abacus, AI-enhanced Finite Element Method Update model and a topological optimization algorithm.

Profiles with skills and knowledge first in mechanical engineering, numerical simulation and additive manufacturing are highly compatible. Supplementary training in micro-nano-fabrication is an additional advantage but is not necessary.

Contexte de travail

The PhD will be co-supervised by Bastien Venzac and Florian Bugarin.
Bastien Venzac is a CNRS researcher in the ELiA team, specialized in in vitro systems for the study of the cell and tissue microenvironment, hosted in the LAAS-CNRS laboratory in Toulouse, France.
Florian Bugarin is an associate professor of the Clement Ader Institute (Toulouse, France), specialized in the numerical simulation by finite element methods of complex materials, including biomaterials and cell organization.

Le poste se situe dans un secteur relevant de la protection du potentiel scientifique et technique (PPST), et nécessite donc, conformément à la réglementation, que votre arrivée soit autorisée par l'autorité compétente du MESR.

Contraintes et risques

This position is subject to the protection of scientific and technical potential (PPST) and, in agreement with regulations, requires prior authorization from the French Ministry of Higher Education and Research (MESR) for recruitment.