Doctoral thesis at the Center for Biomedical and Healthcare Engineering
Mines Saint-Etienne – SAINBIOSE (INSERM-U1059) – Université de Lyon (France)
Mechanical characterization and modeling of a synthetic elastic protein and its effects on the arterial function
Keywords: biomechanics, multiscale models, homogenization, elastin, mechanical characterization, tissue engineering.
Scientific context: Elastin is the main elasticity provider for several soft tissues (such as dermis, arteries, pulmonary alveoli) in its fibrous form and a signaling molecule in cell/extracellular matrix interaction. Elastin-rich elastic fibers allow the large artery walls to transform the pulsatile blood flow ejected by the heart into a continuous blood flow in the peripheral arteries (Windkessel effect). Dysfunctions are highly correlated with diseases such as artery stenosis, aneurysm, hypertension or cardiac hypertrophy, which have strong repercussions on arterial biomechanics and can threaten the vessel integrity.
Setting aside surgery, there is currently no treatment for preventing, blocking or treating any loss of elasticity. It therefore appears, from a biomechanical point of view, that the introduction of an entity that provides elasticity within the arterial wall would be the most trivial action to stop arterial stiffening, but remains currently limited due to chemo-biological issues. The Arterylastic project, to which the thesis is linked, proposes to unlock this technological barrier using an original synthetic elastic protein (SEP) recently developed with a synthetic backbone devoted to skin engineering.
Academic context: As previously mentioned, the thesis takes place in a larger project named Arterylastic, funded by ANR, combining pluridisciplinary approaches of three laboratories in France: LBTI – the Laboratoire de Biologie Tissulaire et Ingénierie Thérapeutique (UMR5305 CNRS/UCBL1 Lyon), HP2 –Hypoxie Physiopathologie Cardiovasculaire et Respiratoire (INSERM U1042 – University Grenoble Alpes) and Sainbiose (within the Center for Biomedical and Healthcare Engineering CISSAINBIOSE/INSERM U1059 – Mines Saint-Etienne). The PhD student will work at CIS, which also conducts major international research projects in the field of soft tissue biomechanics, in particular aortic aneurysms. He will collaborate with other researchers involved in ERC projects (https://www.mines-stetienne.fr/en/author/avril/, https://www.emse.fr/~badel/).
Objectives: The objective is to restore (or at least improve) arterial function and mechanical properties under conditions of elastic fibers injury. The objective will be reached if the SEP is correctly integrated into elastic fibers and if the SEP restores arterial wall elasticity and/or physiological parameters in relevant animal models. In this thesis, we will evaluate the mechanical behavior of the cross-linked SEP and of arterial samples from treated mouse models and a numerical model will be developed from experimental data to better predict treatment parameters.
The main tasks will be:
- Experimental tests will be carried out for characterizing the macroscopic mechanical properties of the SEP and of arteries treated with the SEP. The cross-linked SEP will be characterized using tensile tests with a customized device. Mechanical parameters of treated arteries will be assessed by measuring pressure-diameter curves from mouse arteries tested in a customized tension-inflation test.
- A multiscale numerical model of the mechanical behavior of arteries will be elaborated, taking into account their microstructural composition and morphology (bilayer, specific contributions of elastin, collagen, smooth muscle cells, possible proteoglycans) and including the effects of possible grafting of the SEP to the arterial wall. The model will be tested for arteries with competent elastic fibers, for arteries with damaged elastin and induced-tissue remodelling, and for arteries treated with the SEP.
- The experimental results obtained at task 1 will be used to evaluate and calibrate the prediction ability of the numerical model developed in task 2. Sensitivity analysis permitting to find the optimal treatment conditions with the SEP for different types of therapeutic targets will be addressed.
Candidate profile: Candidates with strong skills in mechanics (modeling and experimental) and biomechanics are expected. Motivation and interest in bioengineering applications is recommended.